CHRONOLOGICAL HISTORY OF
The alchemist Brandt Hennig is credited to have prepared phosphorus (phosphoro mirabile), the first element isolated in a quite pure state.
Tachenius Otto suggested for the first time that an acid compound is hidden in fats since the strength of the alkali disappears when making soap (Hippocrates Chymicus, Paris 1673).
Hensing JT published at Giessen the first monograph on the chemical examination of the brain in which he isolated phosphorus (Cerebri examen chemicum ex eodemque Phosphorus singularem omnia inflammabilia accendentem..., Giessen, Vulpius, 1719). This work was considered as a cornerstone of modern neurochemistry.
First study by Poulletier de la Salle FP of a lipid (cholesterol) isolated from bile stones.
Discovery by the Swedish scientist Scheele CW of glycerol obtained by heating several oils and fats with lead oxide.
Fourcroy AF introduced alcohol to extract brain lipids.
Chevreul M E was born the 31st of August in Angers, the capital of the central French province of Anjou.
Jean Senebier, a famous Swiss scientist, observed that exposure to air causes vegetal oils to loose their fluidity and become rancid (Encyclopédie méthodique, Physiologie végétale, t.1, Paris 1791)
De Saussure NT described experiments showing that linseed oil was able to condense with oxygen (Recherches chimiques sur la végétation, Paris, 1804).
First description by Vauquelin LN of the presence of phosphorus bound to fat in the brain (Analyse de la matière cérébrale de l'homme et de quelques animaux, Ann Mus Hist Nat 1811, 18, 212).
Chevreul ME published his first paper on the composition of animal fats. Description of the concept of fatty acids.
First report by Chevreul ME of the participation of water during the saponification process.
Magendie F in Paris found that olive oil alone did not permit dogs to survive more then one month.
First characterization by Chevreul ME of "cholesterine" in bile stones (Memoires Muséum 1818, 11, 308).
French patent (29 July) by the chemist Braconnot
for the manufacture of candles made of a mixture of bee wax and a purified
fraction from beef tallow ("absolute tallow").
Pelletier PJ et al. used for the first time the word "chlorophyll" to name the purified green pigment of plant leaves (Ann Chim Phys 1818, 9, 194).
The elaidisation reaction was obtained by a French pharmacist, Poutet JJE (Ann Chim Phys 1819, 12, 58) who observed that trioleine could be converted to the consistency of pork lard when treated with nitrogen oxides
Chevreul ME published his masterly work on the chemistry of lipids "Recherches chimiques sur les corps gras d'origine animale" where he described for the first time several fatty acids (margaric, oleic, stearic, butyric and caproic acids), including isovaleric acid (he named it "acide phocénique"), the first branched-chain fatty acid to be isolated from the head oil of dolphin and from porpoise oil.
MH Chevreul and JL Gay-Lussac took a patent for the manufacture of the stearic acid candle. 1825 may be considered as the beginning of oleochemistry.
Prout W, English physician, recognized fat as an important nutrient in the diet along with protein and carbohydrate (Phil Trans 1827, p.355).
Lecanu LR showed the presence of cholesterol in an extract of hen egg yolk (J de Pharm 1829, 15,1).
Wackenroder HWF named "carotin" the hydrocarbon pigment isolated from carrots, as ruby red crystals (Giegers Magazin Pharm 1831, 33, 144).
Boudet demonstrated that only olive oil was able to increase its viscosity under the action of nitrogen peroxyde which generates a new compound, elaidic acid isolated from "elaïdin" (Ann Chim 1832, 50, 391). The elaidisation reaction was discovered by Poutet (1819).
Dumas MJ named "chloroform" the product obtained by
distillation of a mixture of alcohol and calcium chloride in water. Its
structure was erroneously given (C4H2Cl6) (Ann
Chim Phys 1834, 56, 113).
Couerbe J-P introduced diethyl ether to extract brain lipids. He reported the first composition of the brain lipids including a saponifiable fraction (céphalote) soluble in ether and containing 5.8% of phosphorus and a non-saponifiable fraction (cérébrote) containing 2.3% of phosphorus (Ann Chim Phys 1834, 56, 160). Couerbe made the hypothesis that phosphorus may play an important role in the animal brain.
Berzelius JJ named the yellow pigments from autumn leaves xanthophylls (Annalen 1837, 21, 257).
Pelouze and Boudet made for the first time the
hypothesis that oleic acid and "margaric acid" (a mixture of palmitic
and stearic acids) could both be combined in compounds present in vegetal oils (J
de Pharm 1838, 24, 385).
Lecanu LR showed that cholesterol was present in human blood
Fremy E isolated a lipidic substance from the
brain and named it oleophosphoric acid (Ann Chim Phys 1841, 2, 463).
Myristic acid (14:0) is discovered in seeds of the family Myristicaceae by Playfair L (Ann 1841, 37, 152).
Gobley NT described the first instrument devoted to lipids, the "élaïdomètre", he invented to test the purity of oils by determining their density (J Pharm Chim 1843, 4, 285).
First isolation of linoleic acid
("Leinol") prepared from linseed oil by Sacc F (Ann 1844, 51, 213).
Pelouze TJ et al. described for the first time the synthesis of a natural neutral lipid, tributyrin, by the direct esterification of glycerol and butyric acid (Ann Chim Phys 1844, 10, 434).
Claude Bernard demonstrated a lipase activity in the pancreas.
Gobley NT described in egg yolk as in brain the presence of a phosphorus-containing fraction which gave by hydrolysis "oleic acid, margaric acid and phosphoglyceric acid" (J Pharm Chim 1847, 12, 5).
Behenic acid (22:0) is discovered in
bean oil (seeds of Moringa oleifera) by Voelcker A (Ann 1848, 64, 342).
Saalmüller L isolated the first known hydroxy fatty acid, ricinoleic acid (12-hydroxyoleic acid), from castor oil in which it is the principal compound (Saalmüller L, Ann 1848, 64, 108).
First description by Darby S of erucic acid (22:1
n-9) in rapeseed oil (Ann 1849, 69, 1).
Lauric acid (12:0) is discovered in Lauraceae seeds (Laurus nobilis) by Marsson T (Ann 1842, 41, 429).
Claude Bernard discovered that pancreatic juice was involved in the breakdown of fat to glycerine and fatty acids for sunsequent absorption.
Gobley NT isolated from egg-yolk a phosphorus-containing lipid which was named "Lecithin" from the greek lekithos, egg yolk (J Pharm Chim, Paris, 1850, 17, 401).
Chevreul ME showed that paint drying (oxidation
of unsaturated fatty acids) is accompanied by oxygen fixation detected by a
weight increase (Mem Acad Sci 1850, 22, 685-732).
Inositol (hexahydroxycyclohexane) was first isolated from muscle by Scherer. He coined the name 'inositol" from the Greek inos (muscle).
Duffy PJ described the first reaction of lipid interesterification (tristearin with ethanol) (J Chem Soc 1852, 5, 303).
Gerhardt Charles used for the first time the word "glyceride" for the simple compounds forming fats and oils (Traité de Chimie organique, 1853, t.1, 768).
First study of triglyceride
crystallization with the description of three melting points for tristearin (Duffy
PJ, J Chem Soc 1853, 5, 197).
Erucic acid (13-docosenoic acid) was first isolated from rapeseed oil (Websky F, J Prakt Chem 1853, 58, 449).
Description by Berthelot M of the first synthesis of neutral lipids in combining glycerol with fatty acids (synthesis of mono- di- and triglycerides) (Ann Chim Phys 1854, 41, 216).
Heintz WH showed that "margaric acid" discovered by Chevreul was an indefinite mixture of palmitic and stearic acids.
The famous French chemist Würtz Charles proposed the right formula of glycerol (Ann Chim et Phys 1855, 43, 492).
Demonstration by Bernard C of the importance of pancreatic juice and of bile for the digestion and absorption of fats in the duodenum: "Leçons de physiologie expérimentale appliquées à la médecine", Ballière, Paris.
Greville Williams C named "isoprene" the liquid product obtained by distillation from Hevea rubber and determined erroneously its empirical formula as C10H8 (Williams WC, Philos Trans Roy Soc London 1860, 150, 241).
Strecker characterized a nitrogen-containing
substance in bile and named it choline.
Töpler demonstrated the existence of phospholipids in plant seeds (Landw Vers Sta 1861, 3, 85).
Isolation by Beneke GM for the first time in a plant extract (pea seeds) of a compound he believed to be cholesterol (Ann Chem Pharm 1862, 122, 249).
French patent by Mège-Mouriès H for the production of "margarine".
The existence of lipases in plant seeds was noted by Muntz MA (Ann Chem Liebigs 1871, 22, 472).
Bokay A gave the first indication of the existence of enzymes (phospholipases) in pancreatic juice hydrolyzing lecithin into glycerophosphoric acid, fatty acids and choline (Z physiol Chem 1877, 1, 157).
Hesse O isolated from a vegetal extract a compound slightly different from cholesterol (cholesterin) by its composition and melting temperature, he named that new compound "phytosterine" (Ann Chem und Pharm 1878, 192, 175).
Soxhlet Franz, a German chemist, pioneered extraction technology by developing a solid-liquid extraction apparatus that carries his name.
This apparatus was used first to separate fats from food (Dingler's
Polytechnisches J 1879, 232, 461).
Köttstorfer proposed to characterize fats by the saponification index (amount of KOH needed to saponify 1 g of fat) (Z anal Chem 1879, 18, 199).
Bouchardat G obtained isoprene from natural rubber and found that heating isoprene with HCl produced a rubber-like polymer. This was the first production of artificial rubber (Bouchardat G, C R Acad Sci 1879, 89, 1117).
Characterization of an hydroxylated fatty acid, hydroxymyristic acid, extracted from Angelica archangelica oil (Müller R, Ber 1881, 14, 2476).
Publication in London of the masterly work of
Thudichum JLW "A treatise on the chemical constitution of the brain".
Description by Thudichum JLW of the presence of sphingosine in brain lipids after alkaline hydrolysis. He isolated and named sphingomyelin a phospholipid without glycerol but containing choline and sphingosine. He described also the presence of cerebrosides and of a sulfated lipid (sulfatides) in brain extracts. He individualized cephalin (phosphatidylethanolamine) as a phospholipid distinct from lecithin (phosphatidylcholine).
Description by Baron A von Hübl of the iodine index as a measure of fat unsaturation (Dingler's Polytech J 1884, 253, 281).
First description by Peters K of the diene structure of linoleic acid (Monatsch 1886, 7, 522).
Wooldridge LC proposed for the first time that the prothrombin activator is a protein/phospholipid complex.
Salkowski described the presence of
cholesterol in cod liver oil and concluded that animal fats and oils contain
cholesterol while vegetal fats and oils contain phytosterols (Z anal Chem
1887, 26, 557).
First description of the triene fatty acid, linolenic acid, in hempseed oil (Hazura K, Monatsch 1887, 8, 147)
Wallach O described for the first time the chemical structure of terpene compounds (Zur Kenntnis der Terpene und ätherischen Oele, Justus Lieb Ann Chem 1887, 238, 78).
Hazura K et al. described for the first time a procedure to define the number of double bonds in a fatty acid molecule using permanganate oxidation (Hazura K et al. Monatsh Chem 1888, 9, 944).
Chevreul Michel Eugene died the 19th of April in
Paris at the age of 103.
Description by Tanret C of ergosterol in ergot, fungus parasiting "seigle" (rye) (Tanret C, Compt rend Acad Paris 1889, 108, 98).
Arnaud A discovered an acetylenic fatty acid (6-octadecynoic acid or tariric acid) in seed oil of Picramnia, Simarubaceae (Bull Soc Chim 1892, 7, 233).
Schmidt A. discovered that lipid extracts of
various tissues contained a lecithin-rich factor (zymoplastic agent) which was
able to activate blood coagulation.
Gerard was the first to recognize ergosterol in yeast and in fungi in general (Gerard E, Compt rend Acad Paris 1892, 114, 1544).
Goldsobel AG established the right structure of ricinoleic acid (Ber 1894, 27, 3121).
Diesel R developed the first engine to run on peanut oil, as he demonstrated later at the World Exhibition in Paris in 1900.
Overton C observed that liposoluble molecules were able to enter easily into the cells. He proposed that the cell membranes were made of lipids.
Sabatier P et al. described the
hydrogenation of olefinic molecules in the presence of metallic catalyst (C R Acad Sci 1897, 124, 1358),
a discovery for which he wins a Nobel Prize in 1912.
Thoms H proposed the denomination "phytosterol" for all sterols of vegetal origin.
Heise R demonstrated for the first time the presence of mixed glycerides, oleodistearin, in the fat from the kernel of Allanblackia (Guttiferae) (Tropenpflanzer 1897, 1, 10).
Description by Edmed FG of the structure of oleic acid (J Chem Soc 1898, 73, 627).
Altman R et al. introduced acetone in the preparation of phospholipids (separation from fats and cholesterol).
Polyunsaturated fatty acids containing a very high iodine number were first detected during studies of fish oils (Bull H. Chemiker-Zeitung 1899, 23, 1043)
At the Paris exposition, a Diesel engine, built by the French Otto Company, has been run wholly on a vegetal oil (peanut oil) (Nitske WR et al., Rudolf Diesel, pioneer of the age of power, Univ. Oklahoma Press, 1965).
First use of the term "phosphatide"
by Thudichum JLW to designate phosphorus-containing lipids.
Thudichum discovered cerebronic acid (3-hydroxy 24:0) in brain lipids (Die chemische Konstitution des Gehirns der Menschen und der Tiere, Tübingen, 1901).
Hydrocarbons that coat ants cuticle were shown to be used as nest-mate discrimination signals (Fielde AM , PNAS 1901, 53, 521).
First description by Tswett M of a separation
procedure by column chromatography on calcium carbonate of plant pigments with
petroleum ether as eluent (Proc Warsaw Soc Nat Sci 1903, 14).
Patent in England by Normann W for the "conversion of unsaturated fatty acids or their glycerides into saturated compounds" by hydrogenation (Patent N° 1515 A.D. 1903).
First use by Molinari E of the ozonisation method to determine the position of double bonds in fatty chains (Ann Soc Chim Milano 1903, 9, 507).
Kyes P et al. showed that the reaction of lecithin with cobra poison produced a new product they named "cobra-lecithide" which had the property of hemolyzing red blood cells (Berlin klin Wochschr 1903, 40, 57).
Knoop F first proposed that fatty acids were
oxidized at the b-carbon
position (Knoop F, Beitr Chem Physiol Path 1904, 6, 150).
The first cyclopentenyl fatty acid to be isolated from chaulmoogra oil was hydnocarpic acid (from Hydnocarpus Kurzii) by Power FB et al. (J Chem Soc 1904, 85, 838)
An antiphospholipid antibody was first described by Wassermann A in his studies to develop a test for syphilis (Wassermann A et al., Dtsch Med Wochenschr 1906, 32, 745).
Tsujimoto M discovered a hydrocarbon in oils from shark liver he named "squalene" (J Soc Chem Ind Jpn, 1906, 9, 953)
First isolation of arachidonic acid from liver lipids (Hartley P, J Physiol 1907, 36, 17).
Ignatowsky A observed for the first time that feeding cholesterol-rich foods to rabbits produced atheromatous lesions in arteries (Arch Med Exp Anat Pathol 1908, 20, 1).
First description by Erdmann E et al. of the structure
of linolenic acid (Ber 1909, 42, 1334).
Hartley P. is the first who isolated and purified arachidonic acid and determined that it was an eicosatetraenoic acid (Hartley P, J Physiol 1909, 38, 353).
H MacLean introduced cadmium chloride to improve lecithin purification (Z Physiol Chem 1909, 59, 223).
Wallach GO, Professor at Göttingen University,
received the Nobel
Prize "for the services which he has rendered in the development of
organic chemistry and the chemical industry by his pioneering work in the field
of alicyclic compounds" (Nobel
Lecture, December 12, 1910). He proposed that these alicyclic lipids (terpenes)
can be regarded as oligomers of isoprene.
Windaus A determined chemically the presence of high amounts of free and esterified cholesterol in fat droplets found in sclerotic arteries (Hoppe-Seyler's Z Physiol Chem 1910, 67, 174).
First isolation of a ketoalkanoic acid (lactarinic
acid or 6-ketostearic acid) from the mushroom Lactarius refus (Bougault
J et al., C R Acad Sci Paris 1911, 153, 572).
Willstatter R et al. discovered and named "phytol" the alcohol which esterifies the tetrapyrrole nucleus (Ann Chem 1911, 387, 317), it was synthesized in 1928.
Tswett M named "carotenoids" the group of various pigments he has separated from plants (Ber Dtsch Bot Ges 1911, 29, 630)
Howell WH presented the evidence that the
thromboplastic action of tissue juices is a property of the unsaturated
phospholipid cephalin extracted by diethyl ether from dried brain or thymus (Am
J Physiol 1912, 31, 1).
Sabatier P received the Nobel Prize for chemistry (with Grignard V) "for his method of hydrogenating organic compounds in the presence of finely disintegrated metals whereby the progress of organic chemistry has been greatly advanced in recent years".
McCollum EV et al. showed that certain
lipids ("lipins") must be present in the diet during the growth of rat
(J Biol Chem 1913, 15, 167). This was the first description of dietary
accessory factors, now known as lipid-soluble vitamins.
Baumann A et al. demonstrated independently that cephalin (phosphatidylethanolamine) from human brain contained an aminoethyl alcohol (Biochem Z 54, 30 and Biochem Z 1913, 55, 296).
Bordet J et al. described a lecithin-rich activator
(cytozyme) in an alcohol extract of blood platelets (Ann Inst Pasteur 1913,
First demonstration that feeding cholesterol to rabbits induced atherosclerosis (Anitschkow N et al., Centralblatt f. Allg Path U Path Anat 1913, 24, 1).
Arachidonic acid was named in 1913 by Lewkowitsch J. (Lewkowitsch, J. 1913. Chemical Technology and Analysis of Oils, Fats and Waxes. 5th edition. Macmillan, London).
First step by Bloor WR after Chevreul to the
complete recovery of polar lipids from living matter : the use of an
ethanol/ether (3/1) mixture for lipid extraction from blood plasma (J Biol Chem 1914, 17, 377).
Levene PA obtained for the first time and in pure form sphingomyelin and elucidated its composition (J Biol Chem 1914, 18, 453).
Delezenne C et al. showed that the hemolytic "cobra-lecithide" of Kyes (1903) was lecithin from which one unsaturated fatty acid has been removed, they named it "lysocithin" (now lysophosphatidylcholine)(Bull soc chim 1914, 15, 421).
Schmidt E measured for the first time high serum cholesterol levels in patients with xanthomatosis thus recognized as an essential hypercholesterolemia (Dermat Z 1914, 21, 137).
Willstätter RM received the Nobel Prize
for chemistry "for his researches on plant pigments, especially chlorophyll".
McCollum et al. made the first major step to separate the vitamins by postulating the existence of two factors, : "fat-soluble A" and "water-soluble B" (McCollum EV et al., J Biol Chem 1915, 23, 181).
Tsujimoto first assigned the correct
empirical formula C30H50 to squalene, an unsaturated
hydrocarbon he discovered in 1906 in a non-saponifiable fraction of shark liver oil.
McCollum EV et al. suggested the provisional use of alphabetical terms for the "lipin" and other essential ‘‘organic complex(s)’’, determined in 1913 to be necessary for animal growth, using a prefix designating characteristic solubility. Thus they proposed the term ‘‘fat-soluble A’’. Soon this gave way to the term ‘‘vitamin A’’. (McCollum EV et al., J Biol Chem 1916, 24, 491)
Langmuir I discovered the structure
of oil-water films and proposed that fatty acids form a monolayer by orienting themselves vertically with
the carboxyl groups in contact with the surface of the water (Langmuir I, J.
Am Chem Soc 1917, 39, 1848).
Osborne TB et al. demonstrated that essential components for prolonged growth are present in both water soluble and lipid soluble fractions (Osborne TB et al., J Biol Chem 1917, 31, 149).
Cyanolipids, fatty acid esters of branched hydroxy C5 nitriles, were first reported in 1920 to occur in Sapindaceae seed oil ( ). They were shown to be cyanogenic, thus possibly providing a protective function for the plant.
First separation by Twitchell E of unsaturated and saturated fatty acids by lead precipitation (Ind Eng Chem 1921, 13, 806).
Funk C invented the term "Vitamins".
After showing that the antirachitic principle and vitamin A were distinct substances, the group of McCollum EV named the new substance vitamin D (J Biol Chem 1922, 53, 293).
Moureu C et al. named "antioxygene" several phenolic substances which prevent the oxidation of various compounds, including butter and vegetal oils (linseed, wallnut) (C R Acad Sci Paris 1922, 174, 258).
Patent in England by Van Loon C for the
interesterification process of industrial fats (Patent N° 249,916).
Sure B proposed the name vitamin E for a factor which, when absent in diets, was responsible of reproductive failure (J Biol Chem 1924, 58, 693).
Discovery of the UV irradiation process for producing vitamin D in rats (Steenbock H et al., J Biol Chem 1924, 61, 405).
Lieb H identified cerebrosides as the stored material in cells from patients with Gaucher's disease (Hoppe-Seylers Z physiol Chem 1924, 140, 305).
The chemical structure of isovaleric acid (3-methylbutanoic acid) from marine origin was proposed (André E, Bull Soc Chim Fr 1924, 35, 857) after comparison with isovaleric acid from valerian root and a synthetic specimen.
First classification of lipids by Bloor WR (Chem
Rev 1925-26, 2, 243) who recommends the use of the term "Lipides"
as the general group name.
Gorter et al. demonstrated that red blood cells are covered by a layer of fatty substances (glycerophospholipids) that is two molecules thick (a bilayer) (Gorter E et al., Physiol Rev 1925, 51, 66).
Hess AF et al. demonstrated that the factor active in preventing rickets in rats was present in the non-saponifiable moiety of a vegetal oil exposed to UV radiations (Hess AF et al., J Biol Chem 1925, 63, 297). Soon after, they demonstrated that irradiated "phytosterol" or cholesterol was able to confer rickets protection. They hypothesized that UV exposure of the skin is the physiological protection against rickets in animals (Hess AF et al., J Biol Chem 1925, 63, 305).
Car FH and Price EA discovered the
well known color test of vitamin A with antimony trichloride (Biochem J
1926, 20, 497).
The word "Lipid" first appeared in a paper by Sperry WM (J Biol Chem 1926, 68, 357), term including fats and all substances associated with them.
Klenk E discovered and described hydroxynervonic (2-hydroxy 24:1n-9) in brain cerebrosides (Z physiol Chem 1926, 157, 291).
Description of the structure of a biological polyester containing hydroxybutyric acid in the bacteria, Bacillus megaterium (Lemoigne M, Bull Soc Chim Bio 1926, 8, 770)
First isolation by Chibnall AC et al. of
phosphatidic acid from cabbage leaves (Biochem J 1927, 21, 233).
Wieland HO received the Nobel Prize in chemistry for studies "on the constitution of the bile acids and related substances".
Hilditch TP proposed a new chemical method based on potassium permanganate oxidation to appreciate the importance of trisaturated triglycerides in a natural mixture (J Chem Soc 1927, 3106).
Windaus AOR received the Nobel Prize in
chemistry for studies
"on the constitution of sterols and their connection with the
vitamins". The vitamin in question was vitamin D and Windaus was the first
person to receive an award mentioning vitamins.
First demonstration of the presence of "trans" isomers of fatty acids in ruminant depot fats by Bertram SH (Biochem Z 1928, 197, 433).
The structure of phytol was elucidated (Fisher FG et al., Ann Chem 1928, 464, 69).
Introduction of a mixture of diethyl ether/ethanol (1/3) for lipid extraction (Bloor WR, J Biol Chem 1928, 77, 53).
Macheboeuf M isolated from horse serum a
fraction of water-soluble lipoproteins containing 23% phospholipids and 18%
cholesterol (Macheboeuf M, Bull Soc Chim Biol 1929, 11, 485).
Klenk E established that sphingosine contained a straight chain of 18 carbon atoms (Z physiol Chem 1929, 185, 169).
Isolation from tubercle bacilli of the first branched-chain acid (tuberculostearic acid or 10-methylstearic acid) higher than isovaleric acid (Anderson RJ et al., J Biol Chem 1929, 85, 77).
Burr GO et al. reported that fat or rather certain fatty acid components of fat have special nutrient qualities in rats (J Biol Chem 1929, 82, 345).
Moore T proved the in vivo conversion of carotene to vitamin A (Biochem J 1929, 23,803).
Hilditch TP et al. showed that the catalytic hydrogenation of oleate generated new fatty acids which resulted from both geometrical and positional isomerization (Proc Roy Soc London 1929, 552, 563).
Bloor WR established that phospholipids and sphingolipids are efficiently extracted using a mixture of ethanol and ether (3/1) (J Biol Chem 1929, 82, 273).
Burr GO et al. discovered the essentiality of the
long-chain polyunsaturated fatty acids (linoleic and linolenic acids) (J Biol Chem 1930, 86, 587).
Anderson RJ reported the presence of inositol in lipids of tubercle bacilli (J Am Chem Soc 52, 1607).
First demonstration of the biosynthesis of vitamin A from b-carotene in rat, by means of nutritional experiments (Moore T, Biochem J, 1930, 24, 692).
Kuhn R et al. rediscovered the technique of Tswett
(1931) and revived column chromatography in the course of studies on carotenoids
(Z Physiol Chem 1931, 197, 141).
Kuhn R et al. separated for the first time carotene into three isomers, a-carotene, b-carotene, and g-carotene (Chem Ber 1931, 64, 1354).
First use of chloroform replacing ether in the Bloor's mixture (1914) to improve polar lipid extraction (Bornmann JH, J Assoc Off Agric Chem 1931, 14, 489).
The group of Karrer P gave the correct structure of vitamin A (Helv Chim Acta 1931, 14, 1036).
Cummings MJ et al. suggested that vitamin E has specific anti-oxidant capacities (J Nutr 1931, 3, 421).
Windaus A described the right structure of
cholesterol (Ann Rev Biochem 1932, 1, 109).
Description of a fatty acid oxidase activity ("lipoxydase") in soja seeds (André E et al., C R Acad Sci Paris 1932, 194, 645).
Elucidation by Karrer P of the structural formula of the vitamin A (Chemistry at the Centenary (1931) Meeting of the Brit Assoc for Adv of Sci, p. 82. Cambridge: Heffer).
Blix G isolated sulfatide from human brain
after Thudichum (1884) and determined its structure, a sulfated
galactosylceramide (Z Physiol Chem 1933, 219, 82). Its complete
structure was elucidated in 1962.
A balance study enables the demonstration by Schoenheimer R et al. that mice synthesizes less cholesterol after they have ingested (J Biol Chem 1933, 103, 439). This was also the first demonstration that an anabolic pathway can undergo a feedback suppression by end-products.
Description by Noller CR et al. of the synthesis
of oleic acid (J Am Chem Soc 1934, 56, 1563).
Klenk E identified sphingomyelin as the stored phospholipid in cells from patients with Niemann-Pick disease (Hoppe-Seylers Z physiol Chem 1934, 229, 161).
Von Euler US identified a lipid-soluble substance from semen which stimulates uterine smooth muscle contraction and named it prostaglandin (Von Euler US, Arch Exp Pathol Pharmakol 1934, 175, 78)
Klenk E characterized a new type of acidic glycolipid, named substance X (named in 1942 gangliosides), from the brain of patients suffering from amaurotic familial idiocy (Hoppe-Seyler's Z Physiol Chem 1935, 235, 24).
Howell discovered that the platelet factor described
by Bordet in 1913 (cytozyme) was a cephalin (phosphatidylethanolamine) rather
than a lecithin (Physiol Rev 1935, 15, 435).
Toyama Y et al. reported the isolation of an eicosapentaenoic acid from sardine oil which they named timnodonic acid (EPA) (Bull Chem Soc Jap 1935, 10, 192).
Danielli JF et al. described a basic model for the structure of cellular membrane which was accepted by biologists for many years : a "sandwich" of lipids (arranged in a bilayer) covered on both sides with proteins (Danielli J F et al. J Cell Comp Physiol 1935, 5, 495).
Wald G showed how the vitamin A functioned in vision and he gave the name ‘retinene’ (now retinal) to the form of the vitamin present in the retina (Wald G, J Gen Physiol 1935, 19, 351).
Discovered of prostaglandins as biologically active material from prostate by von Euler (Wien Klin Wochenschr 1935, d14, 1182).
Isolation by Evans HM et al. of
a and b-tocopherols
from plant oils (J Biol Chem 1936, 113, 319).
First use by Schoenheimer R et al. of an isotope (Deuterium) to study the in vivo conversion of stearic acid into oleic acid (J Biol Chem 1936, 114, 381). They also demonstrated that [2H]-palmitic acid was not only deposited in the fat but also converted into other fatty acids, including stearic and oleic acids but not linoleic acid, which had been shown earlier to be essential.
First description by Thannhauser SJ et al. of a chromatographic method for phospholipids using an aluminum oxide column (J Biol Chem 1936, 116, 527).
Thannhauser SJ et al. described that a mixture of chloroform and methanol (2/1) is the most efficient for the extraction of phospholipids (J Biol Chem 1936, 116, 533).
Klenk E et al. constructed the first microdistillation device which was capable fractionating a mixture of fatty acid methyl esters (C16 and C18) (Klenk E et al., Physiol Chem 1936, 242, 250). Later on, an improvement of that device was reported (Klenk E et al., Z Physiol Chem 1941, 267, 260).
Quick AJ found that lipid solvents greatly reduce the coagulant activity of tissue extract (thromboplastin) suggesting that the active substance is a lipoprotein (Am J Physiol 1936, 114, 282).
An important component of Mycobacterium tuberculosis wax, phthiocerol, is isolated and its global formula determined (Stodola FH et al., J Biol Chem 1936, 114, 467)
The term "steroids" was coined by Callow RK et al. (Proc Royal Soc London series A 1936, 157, 194) "for the group of compounds comprising the sterols, bile acids, heart poisons, saponins, and sex hormones".
Xanthophylls were named and characterized by Strain HH (Science 1936, 83, 241).
The esterified existence of inositol in lipids
was first described in bacteria (tubercule bacilli) (Anderson RJ, J Am Chem
Soc 1936, 52, 1607).
Moore T first postulated the formation of
conjugated double bonds when linolenic acid was treated with alkali (
Biochem J 1937, 31, 138).
Discovery by Olcott HS et al. of the antioxidant properties of tocopherols (J Am Chem Soc 1937, 59, 1008).
First synthesis of linoleic acid (Noller CR et al., J Am Chem Soc 1937, 59, 522)
Kurz H used ethyl alcohol to derivatize fatty acids (FA ethyl esters) before their analysis (Fette Seifen 1937, 44, 155).
First data on cholesterol and fatty acid metabolism after using an isotope of hydrogen (deuterium) in mice and chicks (Rittenberg D et al., J Biol Chem 1937, 121, 235).
Using deuterated acetate, Sonderhoff R et al. have shown that it serves as a precursor for sterols including ergosterol in yeast (Sonderhoff R et al., Ann Chem Justus Liebigs 1937, 530, 195).
Paul Karrer received the Nobel Prize for chemistry (with N. Haworth) for his investigations on carotenoids, flavins, and vitamins A and B2"
First description of thin-layer chromatography on
a microscope slide coated with aluminum oxide (Izmailov NA et al. Farmatsiya (Mosk.) 1938, 3,
Kuhn R received the Nobel Prize for chemistry "for his work on carotenoids and vitamins".
The correct structure of a-tocopherol is proposed by Fernholz E (J Am Chem Soc 1938, 60, 700).
The group of Karrer P prepared chemically a-tocopherol (vitamin E) (Helv Chim Acta 1938, 21, 520).
Mycolic acids were isolated and named from a waxy extract of human tubercle bacillus (Mycobacterium tuberculosis) (Stodola FH et al., J Biol Chem 1938, 126, 506).
A plant growth-promoting substance, gibberrellin, was crytallized from lipid extracts (Yabuta T et al., J Agric Chem Soc Japan 1938, 14. 1526), but its structure was determined later (1954).
Turpeinen O demonstrated that arachidonic acid is three times more efficient than linoleic acid to cure rats of essential fatty acid deficiency (Turpeinen O, J Nutr 1938, 15, 351).
Feulgen R et al. showed that phospholipid
fractions from heart and brain containing an acetal phosphatide (now
plasmalogen) release fatty aldehydes on acid hydrolysis (Hoppe-Seyler's Z
Physiol Chem 1939, 260, 217).
First detection of inositol and inositol monophosphate in the phospholipid fraction of soybean lipids (Klenk E et al., Z physiol Chem 1939, 258, 33).
Professor Butenandt A was awarded half of the Nobel Prize in Chemistry for his work on sex hormones (steroids), and Professor Ruzicka L was awarded half of the Nobel Prize in Chemistry for his work on polymethylenes and higher terpenes.
Hilditch TP published his most important work "The
chemical constitution of natural fats".
The first description of the urea-fatty acid complexes by Bengen F which revolutionized fat chemistry for about 20 years (German Patent Appl. OZ 12438, march 18, 1940).
Dolby DE et al. discuss the possibility that linoleic acid would represent the physiological precursor of arachidonic acid (Biochem J 1940, 34, 1422).
Lipids containing trehalose were recognized in studies on the lipid composition of Mycobacterium tuberculosis (Anderson RJ, The Harvey Lectures 1940, 35, 271).
First introduction of silicic acid chromatography for lipid separation (Trappe W, Biochem Z 1940, 306, 316).
Trappe W showed that lipids can be eluted in fractions from an alumina column by applying consecutively various solvents of different polarities. Thus, he defined a "eluotropic series of solvents" (Biochem Z 1940, 305, 150).
First characterization of arachidonic acid as 5,8,11,14-eicosatetraenoic acid, a structure consistent with a biochemical origin involving linoleic acid (Dolby DE et al. Biochem J 1940, 34, 1422).
Burr GO and Miller used the alkali conjugation as
a rapid analytical method for determining linoleic acid content of vegetable
Pangborn MC gives the name "cardiolipin" to a lipid isolated from beef heart, and with antigenic properties in the complement-fixation test for syphilis (Proc Soc Exptl Biol Med 1941, 48, 484).
MacFarlane MG et al. demonstrated the presence of a "lecithinase C" (now phospholipase C) in the Clostridium welchii toxin which cleaved phosphorylcholine from lecithin (and sphingomyelin) (Biochem J 1941, 35, 884).
Klenk E isolated a product from a cerebroside fraction for which he introduced the name "neuraminic acid" (Z physiol Chem 1941, 268, 50).
Brückner J described a micro method for the determination of cerebrosides based on the colorimetric determination of galactose by means of orcinol and sulfuric acid (Z physiol Chem 1941, 268, 163).
First description by Klenk E of
"gangliosides", formerly named in 1935 "substance X",
phosphorus-free glycosphingolipids containing sialic acid and present in brain gray
matter and ganglia cells (Hoppe-Seylers Z Physiol Chem
1942, 273, 76).
First description of the correct formula of sphingosine (Carter HE et al., J Biol Chem 1942, 142, 449).
First description by Folch J of a phospholipid containing inositol in the brain (J Biol Chem 1942, 142, 963).
First isolation by Folch J of phosphatidylserine and phosphatidylethanolamine from brain cephalin fraction (J Biol Chem 1942, 146, 35).
Cardiolipin was discovered in beef heart tissue (Pangborn MC, J Biol Chem 1942, 143, 247) but, later, it was recognized to be not specific to the heart.
First liquid chromatography separations of fatty acids concerning short-chain acids by Smith EL (Biochem J 1942, 36, 22).
Farmer EH et al. suggested for the first time that the primary autoxidation product of unconjugated fatty chains is a hydroperoxide formed by the addition of an oxygen molecule to a carbon atom adjacent to the double bond (J Chem Soc 1942, 119).
Von Mikusch JD reported the isolation, from alkali-isomerized acids of castor oil, of the first conjugated linoleic acid (10,12-linoleic acid) (J Am Chem Soc 1942, 64, 1580).
Matsuda S reported the isolation of docosahexaenoic acid (DHA) from fish oil (J Soc Chem Ind Jap 1942, 45, 49).
The role of cholesterol in atherosclerosis was first described in chickens (Dauber DV et al. Arch Pathol 1942, 34, 937)
Description by Arens CL et al. of the right structures
of linoleic and arachidonic acids (Biochem J 1943, 37, 1).
Dam H and Doisy EA received the Nobel prize in Physiology or Medicine for the discovery of vitamin K, its pure preparation, the determination of its chemical structure and the synthetic production of that vitamin.
Cramer DL et al. developed the fractional crystallization of fatty acids or their methyl esters for their isolation from organic solvents at very low temperature, thus avoiding degradation of unsaturated molecules (J biol Chem 1943, 151, 427).
Farmer EH developed the hydroperoxide hypothesis of lipid peroxidation from studies on oleic acid (J Chem Soc 1943 p119 and 541).
The existence of a direct metabolic relationship between cholesterol and bile acids was first established by Bloch K et al. (J Biol Chem 1943, 149, 511).
Arndt F used for the first time diazomethane to derivatize (methylation) fatty acids before chromatography (Org Synth 1943, vol II, 165).
Woolley DW described for the first time the presence of inositol phospholipids in plants (J Biol Chem 1943, 231, 813).
First description by Craig LC of the
countercurrent distribution of organic compounds (J Biol Chem 1944, 155, 519).
First experimental evidence that fatty acids are synthesized by successive condensations of 2 units (acetic acid) (Rittenberg D et al., J Biol Chem 1944, 154, 311).
The formation of mono- and diglycerides
("lower glycerides") was demonstrated to occur during pancreatic
lipolysis both in vitro and in vivo, no free glycerol appearing
during the first 5 hr of the reaction (Frazer AC et al., Biochem J 1945, 39,
Ginger LG et al. isolated a levorotatory fatty acid, mycocerosic acid, from the ‘‘purified waxes’’ of Mycobacterium tuberculosis (Ginger LG et al., J Biol Chem 1945, 157, 203).
Gortner WA established that phospholipids are better quantified by phosphorus determination than with any other methods (Gortner WA, J Biol Chem 1945, 159, 97).
Using deuterium, Rittenberg D et al. obtained evidence that fatty acids are synthesized in mice and rats by condensation of acetic acid (J Biol Chem 1945, 160, 417).
Rhamnolipids were found for the first time in Pseudomonas
pyocyanea growth on glucose (Bergstrom S et al., Ark Kem Mineral Geol
1946, 23A, 1).
Lehninger AL provided the first in vitro evidence of the direct oxidation of a long chain fatty acid by an extrahepatic tissue (J Biol Chem 1946, 165, 131).
First synthesis by Rose WG of a phospholipid,
dipalmitoyl glycerophosphoethanolamine (J Am Chem Soc 1947, 69, 1384).
Carter HE et al. proposed the term "sphingolipide" as a convenient designation for lipids containing sphingosine (cerebrosides, sphingomyelin, gangliosides...) (J Biol Chem 1947, 169, 77).
Carter HE et al. proposed the correct structure of sphingosine, previously discovered by Thudichum JL in 1884 (J Biol Chem 1947, 170, 285).
Hanahan DJ et al. suggested the presence in vegetal tissues of an enzyme (now phospholipase D) producing phosphatidic acid from various phospholipids (J Biol Chem 1947, 168, 233).
Hildtitch TP et al. showed that low temperature crystallization gives more precise data for the analysis of unsaturated fatty acids than the old lead salt separation procedure (J Soc Chem Ind 1947, 66, 284).
The first issue of the journal "Lipids" appeared that year.
Holman RT et al. studied fatty acids by
spectrophotometry after alkaline isomerization at high temperature inducing
conjugation of double bonds (Holman RT et al., Arch Biochem Biophys 1948, 19,
474). By this means, it was possible to measure the content of dienoic,
trienoic, tetraenoic, pentaenoic and hexaenoic acids in lipid extracts.
Separation by Swain LA of unsaponifiable lipids into three fractions on an alumina column (Can Chem 1948, 32, 533).
Successful separation by Boldingh J of methyl esters of long-chain fatty acids by reversed-phase chromatography on filter paper impregnated with vulcanized rubber latex (Experientia 1948, 4, 270).
The process of fatty acid oxidation was discovered to be localized in mitochondria (Grafflin AL et al., J Biol Chem 1948, 176, 95; Knox WE et al., J Biol Chem 1948, 176, 117).
The first time a 14C labeled fatty acid was used to study in vivo its oxidation (Geyer RP et al., J Biol Chem 1948, 176, 1469).
J purified and characterized from the brain cephalin fraction a phospholipid
he named diphosphoinositide (J Biol Chem 1949, 177, 505).
Bolland established that the primary autoxidation products of linoleic acid are hydroperoxides containing conjugated dienes (Q Rev 1949, 3, 1).
Widmer C and Holman RT discovered that linoleic
acid fed to essential fatty acid-deficient rats, was the precursor of
arachidonic acid and that a-linolenic acid was the precursor of pentaene and
First separation by Howard GA and Martin AJP of C12-C18 fatty acids by reversed-phase partition chromatography on kieselguhr impregnated with liquid paraffin and aqueous methanol as eluent (Biochem J 1950, 46, 532).
Baer E et al. achieved the synthesis of phosphatidylcholine via the phosphorylation of a diacylglycerol (J Am Chem Soc 1950, 72, 942).
Raphael RA et al. described the first synthesis of linoleic acid (Nature 1950, 165, 235) and linolenic acid (J Chem Soc 1950, 2100).
Reiser R demonstrated that the high levels of saturated fatty acids in ruminant animal fat are due to the hydrogenation of the dietary unsaturated fatty acids in the rumen (J Nutr 1950, 42, 319).
Asselineau J elucidated the structure of mycolic acids (C R Acad Sci Paris 1950, 230, 1620).
Craig LC gave the first description of a rotary evaporator as a versatile laboratory concentration device enabling the rapid quantitative recovery of solute from large volume of solvents (Craig LC et al., Anal Chem 1950, 22, 1462).
Weinman EO et al. determined that 14C labeled palmitic acid is oxidized in vivo whatever the position of the labeled carbon (J Biol Chem 1950, 184, 735).
Weinman EO et al. determined in vivo for the first time metabolism of phospholipids in which the phosphate group was labeled with 32P and the fatty acid moiety with 14C (J Biol Chem 1950, 187, 643).
Kirchner JG applied for the first time thin layer
chromatography on silica to lipidic compounds
(terpenes from citrus juices) (Anal Chem 1951, 23, 420).
Hanahan DJ et al. purified a phospholipid (phosphatidylcholine) from egg yolk on an alumina column (J Biol Chem 1951, 192, 623).
Baer E described the synthesis of phosphatidic acid by treatment of diacylglycerol with diphenylchlorophosphate and removal of the phenyl group by catalytic reduction (J Biol Chem 1951, 189, 235).
Hofman K et al. discovered cyclopropane (lactobacillic acid) fatty acids in gram-negative bacteria (J Biol Chem 1951, 195, 473).
Yamakawa T et al prepared a ganglioside from horse erythrocytes which contained galactose and neuraminic acid but not hexosamine which they named hematoside (now GM3) (J Biochem 1951, 38, 199).
Zilch KT et al. reported an analysis of fat oxidation product (fatty acids, mono- and diglycerides) by countercurrent distribution methods (Anal Chem 1951, 23, 775).
Discovery of branched-chain fatty acids (odd- and even-numbered carbon from C13 through to C18) in natural fats (butter) (Shorland FB, Biochem J 1951, 51, 207).
Nichols PL et al. reported that alkali-isomerization of linoleic acid gave a mixture of cis-9,trans-11- and trans-10,cis-12-octadecadienoic acid, now known as conjugated linoleic acids (CLA) (Nichols PL et al., J Am Chem Soc 1951, 73, 247).
Folch J et al. described a type of membrane lipoproteins, proteolipids, which are soluble in a mixture of chloroform and methanol (Folch J et al., J Biol Chem 1951, 191, 807).
First description of the countercurrent separation of "the higher normal fatty acids" (C5-C18) (Barry GT et al., J Biol Chem 1951, 188, 299).
Galactosamine was identified in brain gangliosides (Klenk E, Hoppe-Seyler Z Physiol Chem 1951, 288, 216).
First description of the cholesterol lowering effect of a plant sterol (beta-sitosterol) in cholesterol-fed chickens (Peterson DW, Proc Soc exp Biol Med 1951, 78, 143).
Zabin I demonstrates that chain elongation of fatty acids occurred in rat liver in vitro by addition of 2 carbon atoms to the carboxyl end (J Biol Chem 1951, 189, 355).
Borgström B proposed silicic acid as
adsorbent for column chromatography separating neutral lipids and phospholipids
Physiol Scand 1952, 25, 101).
First separation by James AT and Martin AJP of fatty acids up to 12 carbon atoms by "Gas-liquid partition chromatography" (Biochem J 1952, 50, 679).
Martin AJP and Synge RLM received the Nobel Prize for chemistry in part for laying down the basis for partition chromatography.
Mattson FH et al. reported for the first time the presence of 2-monoacylglycerol in the rat intestinal tract as the result of lipolytic action (J Nutr 1952, 48, 335).
For the first time, trans fatty acids were demonstrated by infrared analysis to be present in substantial quantities in a natural product, beef fat (Swern D et al., JAOCS 1952, 29, 44).
Yamakawa T et al. purified from human erythrocytes a ceramide-based glycolipid containing galactosamine but not neuraminic acid which they named globoside (J Biochem 1952, 39, 393).
The first issue of the journal "Progress in the Chemistry of Fats and other Lipids" appeared that year.
First isolation by Faure M et al. of
phosphatidylinositol from wheat germ and heart (C R Acad Sci Paris 1953, 236,
Fillerup DL et al. used a silicic acid column and a stepwise development with diethyl ether-petroleum ether mixtures to fractionate plasma lipid classes (Proc Soc exp Biol 1953, 83, 574).
Lipoic acid (or thioctic acid) is isolated in pure form from beef liver by Reed LJ et al (J Am Chem Soc 1953, 75, 1767).
Yamakawa T et al. found that glycolipid fractions of human erythrocytes inhibited haemagglutination of erythrocytes by ABO blood group antiserum (Jpn J Exp Med 1953, 23, 327).
Discovery of the "phospholipid effect" which results in the generation of diacylglycerol from the hydrolysis of membrane phosphoinositides through the action of a neuromediator, acetylcholine (Hokin MR et al., J Biol Chem 1953, 203, 967).
The long-chain thiokinase which catalyzes the ATP-requiring conversion of fatty acids (C8 to C18) to the corresponding acyl CoA esters was discovered (Kornberg A et al., J Biol Chem 1953, 204, 329).
Lynen F and his group recognize the nature of the b-oxidation cycle of fatty acids (Lynen F et al., Biochim Biophys Acta 1953, 12, 299).
Ruzicka L formulated the "biogenetic isoprene rule" as follows: “…the carbon skeleton of terpenes is composed by isoprene units linked in regular or irregular arrangement.” (Ruzicka L, Experientia 1953, 9, 357).
Woodward RB et al. explained the correct origin of all the carbon atoms of cholesterol (Woodward RB et al., J Amer Chem Soc 1953, 75, 2023).
24-Hydroxycholesterol was detected in human brain and named cerebrosterol (Ercoli IA et al., J Am Chem Soc 1953, 75, 3284). This oxysterol seems to play a role as a physiological regulator of cholesterol homeostasis and as atherogenic factor.
A successful prevention of experimental hypercholesterolemia and cholesterol atherosclerosis was obtained by phytosterol ingestion in the rabbit (Pollak OJ, Circulation 1953, 7, 696) and a reduction of blood cholesterol was similarly obtained in man (Pollak OJ, Circulation 1953, 7, 702).
The physiological function of vitamin D in calcium absorption in the small intestine and the mineralization of the skeleton are described (Nicolaysen R et al., Vitam Horm 1953, 11, 29).
First suggestion by Klenk E et al. of the right
structure of plasmalogens (Hoppe-Seyler's Z Physiol Chem 1954, 296, 179).
Tappel AL proposed a unified theory for vitamin E action as a lipid antioxidant (Tappel AL, Arch Biochim Biophys 1954, 473-485).
Dawson RMC made an important advance in phospholipid methodology in describing the separation of the individual water-soluble products of methanolysis of the total phospholipid fraction (Biochim Biophys Acta 1954, 14, 374).
Carter HE et al. studied phosphoinositol containing sphingolipids in plant extracts (named in 1958 "phytoglycolipids") and described a new long-chain base, phytosphingosine (Carter HE et al. J Biol Chem 1954, 206, 613).
The terpenoid structure of gibberellin, a plant growth-promoting substance, was determined (Curtis PJ et al., Chem Ind 1954, 1066).
Kritchevsky D published the first observation that diets with fats rich in unsaturated fatty acids were less atherogenic for rabbits than those rich in saturated fatty acids (Kritchevsky D et al., Am J Physiol 1954, 178, 30).
Hawthorne JN et al. described for the first time the presence of inositol phospholipids in mammalian tissues (J Biol Chem 1954, 206, 27).
First application by Lea CH et al. of paper chromatography
on cellulose treated with silicic acid for
phospholipid separation (Biochem J 1955, 60, 353).
The first lipoamino acid to be isolated was serratamic acid (hydroxydecanoyl serine) from a strain of Serratia (Cartwright NJ, Biochem J 1955, 60, 238).
Demonstration by Mattson and Beck of a high specificity of pancreatic lipase for triglyceride primary esters (J Biol Chem 1955, 214, 115).
Jensen RG et al. described for the first time the synthesis of mixed acid triglycerides (J Dairy Sci 1964, 47, 1012).
Description of the specific presence of trans fatty acids in the depot fats of ruminants in contrast to their absence in non-ruminants (Shorland FB, Biochem J 1955, 61, 603).
The "phospholipid effect" discovered in 1953 is now attributed to a phosphoinositide in connection with phosphatidic acid metabolism (phosphatidylinositol cycle) (Hokin LE et al.,Biochim Biophys Acta 1955, 18, 102).
Barber JM et al. showed that feeding sitosterol in patients who suffered from coronary artery disease lowered serum cholesterol level (Barber JM et al., Br Heart J 1955, 17, 296).
Svennerholm L showed for the first time that the
ganglioside isolated by Klenk in 1942 was formed at least of two fractions
separated by cellulose column chromatography (Nature 1956, 177, 524).
First separation by Marinetti GV et al. of individual phospholipids by TLC (Biochim Biophys Acta 1956, 21, 168).
First demonstration of the occurrence of different molecular species of phospholipids by Rhodes DN et al. in effecting a partial separation by silicic acid chromatography (Biochem Probl Lipids 1956, Proc 2nd intern conf Ghent, 1955, p 73).
First evidence for the occurrence of glycosylated glycerides by Carter HE, isolating two "lipocarbohydrate" fractions from wheat flour (J Amer Chem Soc 1956, 78, 3735). They were correctly identified in 1961.
Discovery that mevalonic acid is incorporated quantitatively into cholesterol in cell-free systems with loss of carbon dioxide (Tavormina PA et al., J Am Chem Soc 1956, 78, 4498).
The chemical structure of the cord factor of Mycobacterium tuberculosis was established as trehalose dimycolate (Noll H et al., Biochim Biohys Acta 1956, 20, 299).
Discovery of the first polyisoprenoid alcohol, solanesol, in tobacco leaves (Rowland RL et al., J Am Chem Soc 1956, 78, 4680).
First demonstration of the formation of hydroxylated derivatives of cholesterol by mouse liver mitochondria (Fredrickson et al., Biochim Biophys Acta 1956, 22, 183-187).
First efficient separation of fatty acid methyl esters up to 18 carbon atoms by gas-liquid chromatography (James AT et al., Biochem J 1956, 63, 144).
First demonstration that the severity of cholesterol-induced atherosclerosis is a function of the level of saturation of the dietary fats (Kritchevsky D et al., Am J Physiol 1956, 185, 279)
Oxidation with potassium permanganate was used to elucidate the structure of unsaturated fatty acids (von Rudloff E, Can J Chem 1956, 34, 1413)
First isolation by Bergström S of prostaglandins
(Acta Chem Scand 1957, 11, 1086).
Description by Folch J et al. of the most universal method of lipid extraction using a mixture of chloroform/methanol (2/1) (J Biol Chem 1957, 226, 497).
Biggs R et al. demonstrated that all phospholipid fractions showed coagulant activity but none of them was as active as the crude cephalin (Brit J Haematol 1957, 3, 387).
The first bioactive fatty acid amide, N-acylethanolamine, was reported as a constituent of soy lecithin and peanut meal and as a potent anti-inflammatory compound (Kuehl FF et al., J Am Chem Soc 1957, 79, 5577).
First isolation by Carter HE et al. of an ether
phospholipid from egg-yolk (J Biol Chem 1958, 232, 681).
The structure of phosphatidylglycerol was first described (Benson AA et al., Biochim Biophys Acta 1958, 27, 189).
Carter HE et al. described in plant seed extracts new complex sphingolipids with a polar head group containing phosphoinositol, hexosamine and other sugar units, which were named "phytoglycolipide" (JAOCS 1958, 35, 335; J Biol Chem 1958, 233, 1309). These phytosphingosine-containing lipids were the first sphingolipids to be described with structural features of a glycolipid and of a phospholipid.
Morton RA discovered and named ubiquinone (coenzyme Q) in the unsaponifiable fraction of liver lipids (Nature 1958, 182, 1764)
Bernhard K et al. demonstrated that stearic acid could be desaturated aerobically to oleic acid by a mitochondria-free cellular supernatant (Helv 1959, 42, 152).
Demonstration of the effects of medium-chain fatty acids in the diet on the weight maintenance and fat depots (Kaunitz H et al., J Nutr 1958, 64, 513).
First separation of complex lipid mixtures using silicic acid chromatography (Hirsch J et al., J Biol Chem 1958, 233, 311).
Willliam Lands discovered that phospholipids have their fatty acyl composition modified through a remodeling pathway (Lands’ cycle) involving the action of phospholipase A2 and a lysophospholipid acyl transferase (Lands WE, J Biol Chem 1958, 231, 883).
Description by Weicker H (Klin Wsch 1959, 37,
763) and by Mangold HK (Fette Seifen, Anstrichm 1959, 61, 877) of
separations of various lipids by TLC on silica gel .
Bremer J et al. discovered that phosphatidylethanolamine may generate phosphatidylcholine via three successive methylation steps (using in vivo labeled methionine) (Biochim Biophys Acta 1959, 35, 287).
First description of the exact structure of phosphatidylinositol (mainly the diester phosphate link between the 3-carbon of glycerol and the D-1-hydroxyl of the inositol) (Pizer FL et al., J Am Chem Soc 1959, 81, 915).
The first major compositional analysis of the lipids of a virus (Influenza virus) was performed by Frommhagen LH et al. (Virology 1959, 8, 176).
First identification by the Nobel laureate Butenandt A. of a pheromone, 10,12-hexadecadien-1-ol (bombycol), secreted by the female butterfly, Bombyx mori (Butenandt A et al., Z Naturforsch 1959, 14, 283-4).
Benson AA et al. discovered a sulfolipid (sulfoquinovosyl diacylglycerol) in a microalgae Chlorella (Benson AA et al., Proc Natl Acad Sci USA 1959, 45, 1582).
The "Journal of Lipid Research" founded by Ahrens EH of the Rockefeller University of New York appeared that year, 1rst October.
Sjovall J isolated prostaglandin E from sheep prostate
glands and showed that it was a 20-carbon fatty acid with blood pressure-lowering
Myelin was shown to be rich in ethanolamine plasmalogen.
Hawthorne JN proposed a classification of phospholipids, yet adopted (J Lipid Res 1960, 1, 255).
Holman RT et al. showed that, in a few cases, it is possible to fractionate the esters of cis and trans isomeric fatty acids by TLC on silica gel (J Am Oil Chem Soc 1960, 37, 323).
Holman RT described the presence of high amounts of 20:3(n-9) (Mead acid) in animals deprived of essential fatty acids and proposed the triene/tetraene ratio as an indicator of essential fatty acid deficiency (J Nutr 1960, 70, 405).
Kaufmann HP et al. reported the separation of fatty acids by TLC using silica gel layers impregnated with undecane (Fette, Seifen, Anstrichm 1960, 62, 1014).
Pennock JF et al. discovered in human kidney lipids a C100 isoprenoid alcohol which was named dolichol (from Greek dolichos, long) (Pennock RA et al. Nature, 1960, 186, 470).
Roine PE et al. described pathological effects (necrosis and fibrosis) on cardiac tissue of a diet rich in rapeseed oil (rich in erucic acid) (Z Ernährungswiss 1960, 1, 118).
Carter HE et al. identified cerebrosides in wheat flour (Biochim Biophys Acta 1960, 45, 402).
Mycosides are defined as specific glycolipids of Mycobacterial origin. They have the structure of phthiocerol dimycocerosate (Smith DW et al., Nature 1960, 186, 887).
After the report of inositol phospholipids in brain by Folch in 1942, Grado C et al. demonstrated that mono-, di-, and triphosphoinositides were present in bovine brain (Grado C et al., J Biol Chem 1960, 235, PC23).
Dittmer JC and RM Dawson purified PI(4,5P)2 and,
from its phosphate/ inositol ratio of 3:1, called it "triphosphoinositide”
(Biochim Biophys Acta 1960, 40, 379).
Klenk E et al. proposed the preferred metabolic pathway from linolenic to docosahexaenoic acid (Z Physiol Chem 1960, 320, 218).
The most important enzymatic site for the regulation of cholesterol metabolism was identified as the endoplasmic reticulum enzyme, the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) (Bucher NLR et al., Biochim Biophys Acta 1960, 40, 491).
Stoffel W et al. isolated for the first time fish oil fatty acids showing the immense power of GLC for quantitative analysis of highly complex mixtures (Stoffel W et al., J Lipid Res 1960, 1, 139).
The International Union of Biochemists has defined
the nomenclature of phospholipase activities.
Carter HE et al. identified two important glycoglycerolipids in wheat flour, mono- and digalactosyl-diacylglycerol (J Lipid Res 1961, 2, 215 and 223).
Glycoglycerolipids, identified as mannosyldiacylglycerol, were detected for the first time in bacteria (Micrococcus lysodeikticus) (Macfarlane MG, Biochem J 1961, 80, 45).
Dutton HJ et al. described the separation of cis-octadecenoate (oleate) and trans-octadecenoate (elaidate) by countercurrent distribution (Chem Ind 1961, 1874).
The same year, Rachlin A J et al. at Hoffman LaRoche Laboratories (J Org Chem 1961, 26, 2688) and Ege SN et al. at the Boston University (J Am Chem Soc. 1961, 83, 3080) made the first total synthesis of arachidonic acid.
Imai J demonstrated that the oxidative desaturation of a saturated fatty acid (palmitic acid) is depressed in diabetic rats (J Biochem Tokyo 1961, 49, 642).
Kennedy EP described the general pathways of the glycerolipid biosynthesis in animal cells (Fed Proc 1961, 20, 934).
Bremer J et al. characterized a membrane-bound enzyme (PEMT) which converted phosphatidylethanolamine to phosphatidylcholine (Biochim Biophys Acta 1961, 46, 205).
The first total synthesis of a cerebroside is reported (Shapiro D et al., J Am Chem Soc 1961, 83, 3327).
Farnesol (a sesquiterpene) and its derivative farnesal were identified as juvenile hormones in insects (Schmialek PZ, Z Naturforsch 1961, 16b, 461 and Wigglesworth VB, J Insect Physiol 1961, 7, 73).
First separation of glycerides by TLC on silver nitrate impregnated plates
by De Vries B (Chem Ind, London, 1962,
1049) and Barret CB et al. (Chem Ind, London, 1962, 1050) .
Edition by Stahl E of the first book on TLC, "Dünnschicht-Chromatographie, Springer-Verlag, Berlin".
Kaufmann HP et al. reported the reversed-phase separation of fatty acids by a complex two-dimensional TLC employing a catalytic hydrogenation on the plate (Fette, Seifen, Anstrichm 1962, 64, 81).
First description of a direct titration method for analytical hydrogenation to determine precisely the unsaturation of lipids (Brown HC et al., J Am Chem Soc 1962, 84, 1493).
Discovery of O-amino acid (alanyl and lysyl) esters of phosphatidylglycerol in a gram-positive bacteria Clostridium welchii (MacFarlane MG, Nature 1962, 196, 136).
The first GLC analysis of natural triglycerides from milk fat was reported (Kuksis A et al., Can J Med Sci 1962, 40, 679).
Hematoside, the ganglioside of horse erythrocytes, is the first ganglioside (GM3) whose structure was elucidated (Klenk E et al., Z Physiol Chem 1962, 327, 249).
The complete structure of sulfatide (sulfated galactosylceramide) was elucidated including the position of the sulfate group attached to the C3 of galactose (Yamakawa T et al., J Biochem 1962, 52, 226).
Methyl jasmonate was discovered in flowers of jasmine and was shown to be a fragrant component in the essential oil from these flowers (Demole E et al., Helv Chim Acta 1962, 45, 675).
Discovery of diether-type phospholipids in a an extremely halophilic bacteria (Halobacterium cutrirubrum) (Sehgal SN et al., Can J Biochem Physiol 1962, 40, 69).
First demonstration of the presence of 2-aminoethylphosphonic acid and its glycerol ester in lipid extracts of the sea anemone, Anthopleura elegantissima (Kittredge JS et al., Biochemistry 1962, 1, 624).
Demonstration that the extent of absorption of
palmitic acid depends on the form in which it was fed. Absorption is greatest
when palmitic acid is at the sn-2 position of glycerol, and least when it
is fed as a free acid (Mattson FH et al., J Biol Chem 1962, 237, 53).
Steim JM et al. first described the presence of monogalactosyl diacylglycerol in
an animal tissue, the bovine brain (Fed Proc Fed Am Soc Exp Biol 1963, 22, 299).
A sulfonated glycolipid (sulfoquinovosyl diacylglycerol) was discovered in the green alga Chlorella (Benson AA, Adv Lipid Res 1963, 1, 387). That acidic lipid was later shown to be a universal component of photosynthetic tissues.
Hirsch J reported the reversed-phase separation of non polar lipids on a column of polymerized vegetable oil (Factice) (J Lipid Res 1963, 4, 1).
Klenk E et al. showed that the Refsum's disease in human is associated with accumulation of phytanic acid in blood and tissues (Hoppe Seyler's Z Physiol Chem 1963, 333, 133).
First demonstration of the presence of sphingophosphonolipids in lipid extracts of the sea anemone, Anthopleura elegantissima (Rouser G et al., J Am Oil Chem Soc 1963, 40, 425).
Ceramide phosphorylethanolamine was for the first time demonstrated to be present in lipid extract of an insect, Musca domestica (Crone HD et al., Biochem J 1963, 89, 11).
First demonstration of a stimulation of the mitochondrial oxidation of long-chain fatty acids, observations which led the authors to propose for the first time that carnitine played a specific role in the transport of acyl groups through mitochondrial membranes (Fritz IB et al., J Lipid Res 1963, 4, 279).
A uniform nomenclature for the gangliosides was proposed by Svennerholm L (J Neurochem 1963, 10, 613).
The exact structure of four major gangliosides (GM1, GD1a, GD1b, and GT1b) have been reported (Kuhn R et al., Chem Ber 1963, 96, 866; Kuhn R et al., Z Naturforsch 1963, 18b, 541).
Holman RT proposed a new numbering system for the
unsaturation of fatty acids, the "omega nomenclature" (Holman RT,
Fed Proc 1964, 23, 1062).
Block KE and Lynen F were Nobel laureates in physiology and medicine for their discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism (pathway from "activated acetic acid" to the terpenes and fatty acids).
Bergström S et al. demonstrated the enzymatic conversion of arachidonic acid to prostaglandin E2 (Biochim Biophys Acta 1964, 90, 207).
Morrison WR et al. described the famous preparation of fatty acid methyl esters with boron trifluoride (J Lipid Res 1964, 5, 600).
Vaughan M et al. described in detail and assigned the term "hormone-sensitive lipase" to the neutral triacylglycerol lipase activity in adipose tissue which could be increased by lipolytic hormones (catecholamines, glucagon) (J Biol Chem 1964, 239, 401).
Hokin MR et al. suggested that the phosphoinositide effect is initiated by a receptor-activated cleavage of phosphatidylinositol bisphosphate to yield diacylglycerol (Metabolism and physiological significance of lipids, Dawson RMC et al. Eds, J Wiley, London, pp423-434, 1964).
Sophorolipids were first described as surface-active glycolipids in some fungi (Tulloch AP, Can J Microbiol 1964, 10, 359).
The term "phosphonolipids" was proposed by Baer E et al. to describe phospholipids carrying a covalent bond (C-P) between posphorus and the carbon of the nitrogenous base (Baer E et al., J Biol Chem 1964, 239, 3209).
First description of a glycosphingolipid containing a large quantity of fucose (1 out of 4 carbohydrate residues) ("fucolipid") in adenocarcinoma cells from human stomach (Hakomori S et al., J Biol Chem 1964, 239, 3606).
Mattson FH determined that in intestine, triglycerides are preferentially hydrolyzed at position sn-1 and sn-3. Thus, approximatively 75% of glycerol of dietary triglycerides are absorbed as 2-monoglycerides (Mattson F.H et al., J Biol Chem 1964, 239, 2772).
First description of the trans-3-hexadecenoic acid in a seed oil (Hopkins CY et al., Can J Chem 1964, 42, 2224)
Brockerhoff H described an enzymatic procedure to
determine the stereo chemical position of fatty acids in triglyceride molecules
(combination of a pancreatic lipase and a phospholipase A2) (J Lipid Res 1965,
Renkonen O for the first time was able to effectively characterize molecular species of phospholipids after enzymatic removal of the phosphate group (J Am Oil Chem Soc 1965, 42, 298).
Pabon HJJ et al. made the first total synthesis of docosahexaenoic acid (Recl Trav Chim Pays-Bas 1965, 84, 1319).
Cyclohexyl fatty acids were first found in butter (Schogt JC et al., J Lipid Res 1965, 6, 466)
First description of phospholipid vesicles (liposomes) made by mechanical shaking of dried egg phosphatidylcholine with a salt solution (Bangham AD et al., J Mol Biol 1965, 13, 238).
N-acyl phosphatidylethanolamines were discovered in wheat flour (Bomstein RA, Biochem Biophys Res Comm 1965, 21, 49). Later, these compounds, present in plants and animals, were shown to be the source of anandamide.
The structure of ecdysone, a sesquiterpene, was elucidated by Huber R et al. (Chemische Berichte 1965, 98, 2403). Ecdysone is the first hormone discovered in insect.
First description of the specific presence of trans-3-hexadecenoic acid in the phosphatidylglycerol prepared from spinach leaves (Haverkate F et al., Biochim Biophys Acta 1965, 106, 78).
Klenk E demonstrates that the intercoonversion of n-6 (w-6) and n-3 (w-3) fatty acid series does not appear to occur in the animal organism (Klenk E, J Am Oil Chem 1965, 302, 268).
O'Brien JS et al. have demonstrated that some phospholipids isolated from brain tissue are very rich in 22:6n-3 (DHA) (O'Brien JS et al., J Lipid Res 1965, 6, 545).
The accumulating material
in lysosomes in the Gaucher's disease was identified as glucocerebroside
(Brady et al., Biochem Biophys Res Commun 1965, 18, 221).
Morris LJ et al. discovered furanoid fatty acids
in seed oil from Santalaceae (Tetrahedron Lett 1966, 36, 4249).
The structure of a C55 isoprenoid alcohol was described in Lactobacillus and named bactoprenol (Thorne KJL et al. Biochem J 1966, 99, 123).
The presence of compounds similar to insect ecdysteroids (phytoedysteroids) in plants was documented (Galbraith MN et al., J Chem Soc, Chem Comm 1966, 24, 905).
The first issue of the journal "Chemistry and Physics of Lipids" appeared that year.
Rouser G et al. isolated digalactosyl
diacylglycerol from human brain tissue (Lipids 1967, 2, 37).
Diphosphatidylglycerol (cardiolipin) was definitively shown to be localized exclusively to liver mitochondria (Parsons DF et al., in Mitochondrial structure and compartmentation, Quagliariello E et al. Eds, Adriatica Editrice, Bari, 1967, pp. 29-70).
The first component protein of an enzyme of fatty acid biosynthesis, fatty acid synthase, was purified (Simoni RD et al., J Biol Chem 1967, 242, 573).
Polyprenol diphosphates were shown to be involved in the biosynthesis of polysaccharides in Salmonella (Wright A et al., Proc Natl Acad Sci USA 1967, 57, 1798) and in the biosynthesis of peptidoglycans in Micrococcus (Higashi Y et al., Proc Natl Acad Sci USA 1967, 57, 1878).
The structure of juvenile hormone of insects was elucidated by Roller H (Angew Chem 1967, 79, 190).
A Schiff base of retinal and phosphatidylethanolamine was tentatively identified by Adams RG in bovine rod outer segments (Adams RG et al., J Lipid Res 1967, 8, 245).
Using growth and mortality records, Lee DJ et al. demonstrated the essentiality of n-3 fatty acids in trout (Lee DJ et al., J Nutr 1967, 92, 93)
First indication by Fisher DB et al. of a
relationship between inositol lipids and cell proliferation (lymphocytes
stimulated with phytohaemagglutinin) (Proc Natl Acad Sci USA 1968, 60, 1396).
First description of a "peptidelipid" surfactant (surfactin) composed of seven amino acids and one fatty acid (cyclic lipopeptide) produced by Bacillus subtilis (Arima K et al., Biochem Biophys Res Comm 1968, 31, 488).
Marcel YL et al. proposed the preferred metabolic pathway from linoleic to arachidonic acid (Biochim Biophys Acta 1968, 164, 25).
First description of the structure
of a cyanogenic lipid found in a Boraginaceae (Cordia verbenacea)
(Mikolajczak KL et al., Lipids 1969, 4, 617).
First report of the exact structure of a ceramide phosphorylethanolamine and a ceramide phosphorylglycerol in the lipids of an anaerobic bacterium (LaBach JP et al., J Lipid Res 1969, 10, 528).
Discovery of glucosylated phosphatidylglycerol in the gram-positive bacteria Bacillus megaterium (MacDougall JC et al., Biochem J 1969, 114, 361).
The structure of complex phosphorylated glycolipids (glycophosphoceramides or "phytoglycolipids") were elucidated by the group of Carter HE in plant extracts (Carter HE et al., Biochemistry 1969, 8, 383).
The b-oxidation of fatty acids was demonstrated to take place in a newly discovered organelle, the glyoxysome (Cooper TG et al., J Biol Chem 1969, 244, 3514; Hutton D et al., Plant Physiol 1969, 44, 508).
First discovery of unusually high levels of certain prostaglandins in an invertebrate animal, the octocoral Plexaura hornomella (Weinheimer AJ et al., Tetrahedron Lett 1969, 59, 5185).
Durell and his coworkers suggested that triphosphoinositide hydrolysis was connected to acetylcholine receptor activation (Durell J et al. Ann N Y Acad Sci 1969, 165, 743).
Z Physiol Chem 1970, 351, 635) reported the formation of sphingosine-1-phosphate
in erythrocytes, a kind of phosphosphingolipid which appeared later involved
in cellular proliferation.
The name lipoteichoic was coined when teichoic acid lipid complexes were detected in the wall of gram-positive bacteria (Wicken AJ et al., J Gen Microbiol 1970, 60, 293).
The Seven Countries study has revealed that there is a close connection between the amount of dietary saturated fatty acids and the frequency of heart attacks (Circulation 1970, 41, I186).
Identification of 1,25-dihydroxycholecalciferol,
a new kidney hormone controlling calcium metabolism (Lawson
DE et al., Nature 1971, 230, 228).
Boyle IT et al. demonstrated that 1,25-dihydroxycalciferol was the most potent component for calcium absorption by the intestine (Proc Ntl Acad Sci USA 1971, 68, 2131).
First efficient assay
to extract bone lipids (Shapiro IM, Arch oral Biol 1971, 16, 411).
Bretscher MS proposed that both leaflets of the
lipid bilayer of biological membranes have different lipid compositions, thus
defining an asymmetric structure (Nature
New Biol 1972, 236,11)
Yavin E et al. demonstrated that the cleavage of the vinyl-ether linkage of plasmalogens may be done via an oxygen-dependent reaction (ferrous-ascorbate complex) which is inhibited by antioxidants (Eur J Biochem 1972, 25, 437).
Borensztajn J et al. reported an increase of adipose lipoprotein lipase activity in rats after insulin injection (Am J Physiol 1972, 223, 1271).
Bang HO et al. reported that Greenland Eskimos had lower levels of serum cholesterol, low density lipoprotein and triglycerides correlated with a low myocardial infarction rate as compared with Danish controls (Acta med Scand 1972, 192, 85).
Kornblatt MJ et al. discovered the presence of sulfate esters of glycoglycerolipids (a mixture of sulfated alkylacyl, known as seminolipids, and diacyl glycerol) in rat testis (Biochem Biophys Res Commun 1972, 48, 1489).
Galliard T et al. described the structure of two new divinyl ether fatty acids (colneleic and colnelenic acids) generated in potato homogenates by the action of 9-lipoxygenase and divinyl ether synthase (Galliard T et al., Biochem J 1972, 129, 743).
Discovery of the platelet activating factor (PAF) as an alkyl acetyl phosphatidylcholine, one of the first and the most important lipid mediator known (Benveniste J et al., J Exp Med 1972, 136, 1356).
A model of cell membrane architecture, known as the fluid mosaic model, with globular proteins floating within the phospholipid bilayer was proposed by Singer S J et al. (Science 1972, 175, 720).
It was established that lipid compounds containing arsenic and bromine are present in marine organisms (fish and seaweed oils) (Lunde G, JAOCS 1972, 49, 44).
Strigolactones, terpenoids derived from carotenoids (apocarotenoids) were demonstrated to be germination stimulants in plants (Cook CE et al., J Am Chem Soc 1972, 94, 6198).
Gordesky SE et al. demonstrated that nearly all
phosphatidylserine and a minimum of 70% of phosphatidylethanolamine is on the
inside surface of the human erythrocyte membrane, thus "presenting a strong
evidence for an asymmetric arrangement of phospholipids" (Biochem
Biophys Res Comm 1973, 50, 1027).
First demonstration of an inhibition of sterol biosynthesis (HMG-CoA reductase activity) by oxygenated derivatives of cholesterol in cultured mammalian cells (Kandutsch AA et al., J Biol Chem 1973, 248, 8408-8417).
For the first time, the existence of polyunsaturated fatty acids was reported in marine bacteria (Oliver JD et al., Int J Syst Bacteriol 1973, 23, 442).
Riley CA et al. first reported
that hydrocarbon gases were released by mice upon treatment with CCl4 due
to lipid peroxidation (Science 1974, 183, 208).
Banschbach MW et al. demonstrated that acetylcholine is able to increase diglyceride levels in incubated pancreatic tissue (Biochem Biophys Res Comm 1974, 58, 714).
Inositol phosphorylceramide was shown to be a novel phospholipid in yeast (Smith SW et al., J Biol Chem 1974, 249, 3395).
The first structure of a betain lipid (diacylglyceryl hydroxymethyl trimethylhomoserine) was reported in a vegetal Ochromonas danica (Brown AE et al., Biochemistry 1974, 13, 3476).
Wallen LL et al. reported the identification of hydroxyalkanoates biological polyesters containing carbon chains different from hydroxybutyrate (Wallen LL et al., Environ Sci Technol 1974, 8, 576)
Studies on the amino acids in the vitamin K-dependent region of prothrombin indicate that vitamin K is involved in the derivatization of glutamic acid by g-carboxylation (Nelsestuen GL et al., J Biol Chem 1974, 249, 6347).
Michell RH in a famous review proposed for the
first time that the "phosphoinositide effect" discovered in 1953 by
Hokin plays a role in cellular calcium mobilization (Biochim Biophys Acta
1975, 415, 81).
Flynn TJ et al. reported the isolation of sulfogalactosyl diacylglycerol from the brain of young rats (Biochem Biophys Res Comm 1975, 65, 122).
Using various purified phospholipases the organization of phospholipids in human red cell membranes was established for the first time (Zwaal RFA et al., Biochim Biophys Acta 1975,406, 83).
Fisher KA demonstrated by freeze-fracture and biochemical
analysis in human erythrocytes that cholesterol is asymmetrically distributed
across the plane of the membrane, being more present on the exterior side than
on the interior side (Proc
Nat Acad Sci USA 1976, 73, 173)
Sporn MB et al. introduced the term retinoid to cover all natural as well as synthetic structural analogs of retinol (Fed Proc 1976, 35, 1332).
Endo A et al. discovered the first inhibitor of cholesterol biosynthesis through the inhibition of HMG-CoA reductase, mevastatin (the first statin) extracted from Penicillium citrinum (Endo A et al., J Antibiot 1976, 29, 1346).
Hopanols have been described in living bacteria (Rohmer M et al., Tetrahedron Lett 1976, 40, 3633).
The asymmetric distribution of phosphatidylserine and phosphatidylethanolamine was determined in human platelet plasma membrane (Schick PK et al., J Clin Invest 1976, 57, 1221).
Discovery in the gram-positive bacteria
Streptococcus of glucosylated diphosphatidylglycerol (cardiolipin) (Fisher
W, Biochim Biophys Acta 1977, 487, 74).
Pieringer J et al. demonstrated a close association of the sulfogalactosyl diacylglycerol of rat brain with the process of myelination (Biochem J 1977, 166, 421).
First description of a high content in EPA (20:5n-3) in a prokaryote, the marine bacterium Flexibacter polymorphus (Johns RB et al., Arch Microbiol 1977, 114, 267).
A full picture of the asymmetric distribution of pig platelet membrane phospholipids was given (Chap HJ et al., Biochim Biophys Acta 1977, 467, 146).
A new membrane lipid, archaeol (diphytanyl glycerol
ether) is discovered by Kates M in halophilic bacteria (Prog Chem Fats Lipids
1978, 15, 301).
Dyerberg J et al. make the hypothesis that eicosapentaenoic acid (EPA) plays a role in the prevention of thrombosis and atherosclerosis (Lancet 1978, 2, 117).
Discovery of sulfated glyceroglycolipids in rat brain (Ishizuka I et al., J Biol Chem 1978, 253, 898).
A strong positive relationship was reported between the docosahexaenoic acid (DHA) content of cardiac phospholipids and the heart rate of mammals ranging in size from mice to whales (Gudbjarnason S et al., Acta Biol Med Ger. 1978, 37, 777)
First demonstration of a Vitamin K dependence of a calcium-binding protein (osteocalcin) containing g-carboxyglutamic acid in chicken bone (Hauschka PV et al., J Biol Chem 1978, 253, 9063)
Low MG et al. discovered in bacteria a specific release of plasma membrane enzymes by a phosphatidylinositol-specific phospholipase C (Biochim Biophys Acta 1978, 508, 565).
Murphy RC et al. elucidated the structure of the
slow reacting substance (SRS-A) of anaphylaxis as a new hydroxylated derivative
of arachidonic acid which was named leukotriene (Proc
Ntl Acad Sci USA 1979, 76, 4275).
Demopoulos CA et al. elucidated the structure of the Platelet-Activating Factor (PAF) as an acetylated alkyl phosphatidylcholine (J Biol Chem 1979, 254, 9355).
The Nishizuka team described unsaturated diacylglycerol as a possible messenger for the activation of a calcium-activated, phospholipid-dependent protein kinase system (Biochem Biophys Res Comm 1979, 91, 1218).
Bell RL et al. provided evidence that arachidonate release from stimulated platelets involves a diglyceride lipase acting on the diglycerides produced by a phosphatidylinositol-specific phospholipase C (Proc Natl Acad Sci 1979, 76, 3238).
Dyerberg J et al. suggested for the first time a close relationship between platelet aggregation, bleeding time and n-3 polyunsaturated fatty acids (Lancet 1979, 2, 433).
Walker IC et al. identified a new epoxy-hydroxy fatty acid (hepoxilin) after incubation of blood platelets with arachidonic acid (Prostaglandins 1979, 18, 173).
A wound hormone in plant, traumatin, was identified as 12-oxo-trans-10-dodecenoic acid (Zimmerman DC et al., Plant Physiol 1979, 63, 536).
Lysophosphatidylserine was shown to be specifically required for histamine release from rat peritoneal mast cells stimulated by concanavalin A, this lyso compound being 1000 times more potent than diacylphosphatidylserine (Smith GA et al., FEBS Lett 1979, 105, 58).
Porter NA et al. demonstrated for the
first time the free radical oxidation of membrane phospholipids (Lipids 1980,
Low MG et al. demonstrated clearly that alkaline phosphatase is attached to membranes of Staphylococcus aureus by a strong interaction with phosphatidylinositol (Low MG et al., Biochemistry 1980, 19, 3913). The discovery of these "anchor" molecules had a significant impact on several areas of cell biology.
Discovery of vitamin A2 (3,4-didehydroretinol) in the human epidermis (Vahlquist A, Experientia 1980, 36, 317).
First description of an association of vitamin K with vascular calcification (Levy RJ et al., J Clin Invest 1980, 65, 563).
Nishizuka and coworkers demonstrated
that protein kinase C (PKC) responded to neutral lipids, more specifically
diacylglycerol (DAG) (Kishimoto A et al., J Biol Chem 1980,255, 2273).
Michell RH et al. identified phosphatidylinositol-4,5-bisphosphate
as the main phospholipid subject to a turnover in stimulated cells in connection
with calcium mobilization (Philos Trans R Soc, London B, 1981, 296, 123).
Fredrikson G et al. described the first extensive purification of the hormone-sensitive lipase of adipose tissue (J Biol Chem 1981, 256, 6311).
24(S),25-Epoxycholesterol was discovered in 1981 when Nelson et al. showed that it is formed from acetate during the normal course of cholesterol biosynthesis in rat liver homogenates (Nelson JA et al., J Biol Chem 1981, 256, 1067).
First description of the possibility of curing neuropsychiatric disorders with a diet enriched in linolenic acid (flaxseed oil) (Rudin DO, Biol Psychiatry 1981, 16, 837).
Eberhard A et al. identified the autoinducer of Photobacterium fischeri luciferase as an aminolipid, N-(3-oxohexanoyl) homoserine lactone (Biochemistry 1981, 20, 2444). Several N-acyl homoserine lactones were later shown to be largely present in Gram-negative bacteria, playing the role of quorum-sensing signals.
First demonstration of an anti-proliferative effect of 1,25-dihydroxyvitamin D3 on cultured human cancer cells. It was demonstrated that vitamin receptors were present and that nanomolar concentrations of vitamin inhibited the growth of human melanoma cells (Colston KW et al., Endocrinology 1981, 108, 1083).
Bergström SK , Samuelsson BI and Sir Vane JR received
the Nobel Prize for medicine "for their discoveries concerning
prostaglandins and related biologically active substances". Their work
established the relationships between fatty acids, prostaglandins, thromboxanes
and leukotrienes (they discovered) and helped explain the effects on the body
of aspirin, the world's most widely used drug.
Nakamura T et al. discovered 4-hydroxynonenal (4-HNE) in autoxidized linseed oil (Bull Jap Soc Sci Fish 1982, 48, 1357).
Bevers EM et al. reported that the activation of blood platelets triggered a change in the distribution of lipids in the plasma membrane: phosphatidylserine becomes exposed at the outer surface (Eur J Biochem 1982, 122, 429).
Grove RI et al. demonstrated that a tumor promoter (phorbol ester) caused in chick embryo myoblasts increased diacylglycerol levels generated via the hydrolysis of phosphatidylcholine (Biochim Biophys Acta 1982, 711, 272).
Macrae R et al. used for the time a HPLC detection system for lipids based on evaporative light-scattering (Chromatographia 1982, N° 7, july).
Agrawal HC et al. demonstrated for the first time that proteolipids contain covalently-bound fatty acids (Agrawal HC et al., J Biol Chem 1982, 257, 4588).
Schwartz RS et al. described the mechanism of the regulation of lipogenesis by fatty acids in measuring the rate of synthesis of fatty acid synthase in mouse liver (Schwartz RS et al., Biochim Biophys Acta 1982, 711, 316).
Holman RT et al. described a case of linolenic acid deficiency involving neuronal abnormalities. As for trout (1967), linolenic acid is recognized as essential for human (Holman RT et al., Am J Clin Nutr 1982, 35, 617).
It wasdemonstrated for the first time that lysophosphatidic
acid with an O-alkyl ether group was very potent in promoting platelet aggregation
(Simon MF et al., Biochem Biophys Res Comm 1982, 108, 1743).
Streb H et al. have shown that inositol-1,4,5-trisphosphate (IP3) is capable to release calcium from non-mitochondrial pools in pancreatic cells, this report providing information on the role of phosphatidylinositol 4,5-bisphosphate in stimulus-coupled responses (Nature 1983, 306, 67).
Berridge demonstrated that IP3 was clearly the product formed first by hydrolysis of polyphosphoinositides instead of phosphatidylinositol after blowfly salivary glands were stimulated (Berridge MJ, Biochem J 1983, 212, 849).
Dubacq JP et al. demonstrated that the chloroplast membranes contain the fatty acyl group trans-3-hexadecenoic acid which is always found esterified to the second position of phosphatidyl glycerol (Dubacq JP et al., Physiol Veg 1983, 21, 293).
Serhan CN et al. discovered new biologically active compounds
derived from arachidonic acid in
human leukocytes, lipoxins A and B (Proc
Ntl Acad Sci USA 1984, 81, 5335).
Seigneuret M et al. discovered in erythrocytes an ATP-dependent aminophospholipid-specific transporter (translocase) which transports phosphatidylserine and phosphatidylethanolamine from the outer to the inner leaflet of plasma membranes (Proc Natl Acad Sci 1984, 81, 3751).
Evidence was given for a post-translational modification of proteins by incorporation of isoprenoid lipids (Schmidt RA et al., J Biol Chem 1984, 259, 10175).
New aldehydic products of the cyclooxygenase pathway, levuglandins, have been discovered (Salomon RG et al., J Am Chem Soc 1984, 106, 6049).
Brown MS and Goldstein JL received the Nobel prize
for medicine "for their discoveries concerning the regulation of cholesterol
Bocckino SB et al. brought evidence that phosphatidylcholine breaks down in response to several agonists generating diacylglycerols (J Biol Chem 1985, 260, 14201).
First demonstration by Wolf RA et al. of a plasmalogen selective phospholipase A2 in heart tissue (J Biol Chem 1985, 260, 7295).
Pentchev PG et al. demonstrated that Niemann-Pick disease type C is a disease of cholesterol metabolism (Proc Natl Acad Sci USA 1985, 82, 8247).
Sucrose esters were characterized in lipids of
tobacco leaf (Severson RF et al. J Agric Food Chem 1985, 33, 870). These
particular glycolipids were later shown to have antibiotic and insecticide properties.
The composition and the structure of a novel phosphatidylinositol-containing glycolipid, now known as membrane anchor, were reported in a protozoan Trypanosoma brucei (Ferguson MAJ et al., J Biol Chem 1985, 260, 14547).
Experiments on Torpedo electric organ led to the suggestion that acetylcholinesterase is anchored to the plasma membrane by one or more phosphatidylinositol molecules linked to a short amino acid sequence at one end of the catalytic subunit of the enzyme (Futerman AH et al. Biochem J 1985, 226, 369).
First report that fish oils reduced thickening of vein intimal in graft experiments in dogs (Landymore RW et al., J Thorac Cardiovasc Surg 1985, 89, 351).
First published paper in which mutants of Arabidopsis thaliana were used to elucidate the role of a plant lipid, tr-3-hexadecenoic acid (Browse JA et al., Science 1985, 227, 763).
Results from metabolic experiments suggest that 24,25-epoxycholesterol may participate in the regulation of hepatic cholesterol metabolism in vivo (Spencer TA et al., J Biol Chem 1985, 260, 13391).
C hemical surveys of Ophrys bee pollinated species have identified floral volatile lipid constituents including various terpenes, alcohols, ketones and carboxylic acids (Borg-Karlson AK et al., Chem Script 1985, 25, 283).
Serhan CN et al. described the structure and
formation of various lipoxins by leukocytes (J
Biol Chem 1986, 261, 16340).
Stremmel W et al. brought evidence that movement of free fatty acids through hepatocyte plasma membrane is facilitated by a specific binding protein (FABP) (PNAS USA 1986, 83, 3584).
Brassell SC et al. first demonstrates the reliability of a new stratigraphic technique for climatic assessment utilizing the relative abundance of two C37 alkenones in marine sediments (Brassell SC et al., Nature 1986, 320, 129).
First demonstration of a specific receptor-mediated release of 20:4n-6 and 22:6n-3 from plasmalogen phospholipids (Horrocks LA et al., Adv Cyclic Nucl Prot Phosphoryl Res 1986, 20, 263).
Evidence is given that phosphatidic acid is a lipid second messenger with growth factor-like properties, stimulating the breakdown of phosphoinositides and calcium release (Moolenaar WH et al., Nature 1986, 323, 171).
Demonstration of an inhibition of protein kinase C by sphingosine which suggested an important role for that lipid in the regulation of the signal transduction pathways (Hannun YA et al., J Biol Chem 1986, 261, 12604).
First clear demonstration of a formation of diacylglycerol as second messenger from phosphatidylcholine in hormone-stimulated cells (Besterman JM et al., PNAS 1986, 83, 6785).
Abscisic acid, one of the most important phytohormones, has been shown to be present in the central nervous system of pigs and rats (Le Page-Degivry MT et al., Proc Natl Acad Sci USA 1986, 83, 1155).
After the discovery of 20:5n-3 in a marine bacterium (Johns RB et al., 1977), a study on 11 piezophilic bacteria (from 1200 to 10 476 m of sea depth) revealed they produced EPA (20:5n-3) and DHA (22:6n-3) in increasing proportion of total fatty acids when pressure increased (DeLong EF et al., Appl Environ Microbiol 1986, 51, 730).
Whitman M et al. identified a
phosphatidylinositol kinase that phosphorylates the D-3 position on the inositol
ring to produce phosphatidylinositol 3-phosphate (PI-3-P) (Biochem
J 1987, 247, 165).
Bocckino SB et al. provided evidence that in hormone-treated hepatocytes phosphatidic acid levels increase by a mechanism involving phospholipase B (J Biol Chem 1987, 262, 15309).
Investigating the carcinogenic components of grilled beef, Ha YL et al. demonstrated for the first time the presence of conjugated linoleic acids (CLA) in animal products which were shown to inhibit mutagenesis in bacteria and the initiation of epidermal carcinogenesis in mice (Carcinogenesis 1987, 8, 1881).
Discovery of a hormone-like compound, a sesquiterpenoid (methyl farnesoate) in crustaceans, now considered as the crustacean juvenile hormone (Borst DW et al., Insect Biochem 1987, 17, 1123).
Demonstration of ceramide generation from sphingomyelin after activation of an acid sphingomyelinase by diacylglycerols (Kolesnick RN et al., J Biol Chem 1987, 262, 16759). First suggestion that sphingolipid-derived metabolites could function as second messengers.
The nest-mate discrimination systems in ants are shown to be based on hydrocarbons (Bonavita-Cougourdan A et al., J Entomol Sci 1987, 22, 1).
Description by Bitbol M et al. of an ATP-dependent
flippase in erythrocytes which transports aminophospholipids and cholinephospholipids
from the inner to outer leaflet (Proc
Natl Acad Sci 1988, 85, 6783).
Demonstration by Hungund BL et al. of fatty acid ethyl ester synthesis in liver of mice treated with ethanol inhalation (J Chem Pharmacol 1988, 37, 3001).
First literature use of the term biodiesel in a Chinese paper by Wang R et al. (Taiyangneng Xuebao 1988, 9, 434).
Description of a specific phosphatidylinositol kinase (PI3K) which produces a novel phospholipid, phosphatidylinositol-3-phosphate (Whitman M et al., Nature 1988, 332, 644).
First report of the receptor-activation of phospholipase D in mammalian cells with generation of diacylglycerol from phosphatidylcholine (Pai JK et al., Biochem Biophys Res Comm 1988, 150, 355).
The importance of diacylglycerol in the fatty acid activation of protein kinase C was reported for the first time in rat brain and bobine spleen preparations (Verkeest V et al., Biochem Biophys Res Comm 1988, 152, 825).
Dietary fish oil supplementation
has been shown to improve vasodilator responses in atherosclerotic coronary
culature principally through the increased release of endothelium-derived relaxing factor now identified as nitric oxide (Shimokawa H et al., Circulation 1988, 78, 1421)
First description of a "sphingomyelin
cycle" related to cell differentiation which generates ceramide and choline
phosphate through the stimulation by vitamin D3 (Okazaki
T et al., J Biol Chem 1989, 264, 19076).
Sphingosine, a constituent and metabolite of membrane sphingolipids, was shown to inhibit protein kinase C, thus playing a pivotal role in a specific signal transduction system (Merrill AH et al., Biochim Biophys Acta 1989, 1010, 131).
Abscissic acid was shown to be a plant lipid mediator involved in the root movement (root gravitropism) in connection with red light and entry of calcium in the cytoplasm of root cells (Leopold AC et al., Plant Physiol 1989, 89, 875).
First demonstration that lysophosphatidic acid is able to induce cell proliferation, a signaling pathways mediated by G proteins (van Corven EJ et al., Cell 1989, 59, 45).
The complete amino acid sequence of
chicken fatty acid synthase has been determined from the corresponding cDNA
KP et al., PNAS 1989, 86, 4387).
Morrow JD et al. discovered new prostaglandin-like
molecules (F2 isoprostanes) produced by free-radical-catalyzed mechanism which
were termed isoprostanes (Proc
Natl Acad Sci 1990, 87, 9383).
Issemann I et al. identified a peroxisome proliferator-activated receptor (PPAR) and cloned a novel member of the nuclear receptor superfamily (steroid hormone receptors). Among activators, a variety of endogenously present lipids were described (Nature 1990, 347, 645).
An antiphosphatidylcholine antibody was described in the serum of a patient diagnosed with hemolytic anemia (Cabral AR et al., J Autoimmun 1990, 3, 773).
Phosphatidylserine was shown to be recognized by specific antibodies in patients with lupus anticoagulant (Zuazu-Jausoro I et al., Med Clin 1990, 95, 210).
The "Nod factors" produced in legumes by Rhizobia as a class of signalling molecules was identified as lipo-chitooligosaccharides (Lerouge P et al., Nature 1990, 344, 781).
First demonstration of phosphatidylinositol anchor on the lipopolysaccharides of a prokaryotic species, Mycobacterium tuberculosis ( Hunter SW et al., J Biol Chem 1990, 265, 9272).
Demonstration of the induction of the synthesis of proteinase inhibitors by methyl jasmonate in a wounded plant but also in nearby plants through the atmosphere (Farmer EE et al., Proc Natl Acad Sci 1990, 87, 7713).
First clear demonstration that trans fatty acids are as unfavorable as saturated fatty acids in raising LDL cholesterol and lowering HDL cholesterol levels (Mensink RP et al., N Engl J Med 1990, 323, 439).
The structure and regulation of a mammalian long-chain acyl-CoA synthetase have been described (Suzuki H et al., J Biol Chem. 1990, 265, 8681).
Work from S. Spiegel and her group found that in fibroblasts sphingosine induced cell growth, in contrast to most other cell types where it functioned as a growth suppressor (Zhang H et al., J Biol Chem 1990, 265, 76).
Demonstration of a "phospholipid scrambling" in the cellular plasma membranes (Comfurius P et al., Biochim Biophys Acta 1990, 1026, 153).
The cloning of cDNA for a lipid transfer protein
in maize (Zea mays) introduced for the first time molecular biology into
plant lipid research (Arondel
V et al., Gene. 1991, 99, 133)
Evidence that sphingosine-1-phosphate is a component of the intracellular second messenger-mediated calcium release is presented (Zhang H et al., J Biol Chem 1991, 114, 155).
Evidence that sphingosylphosphorylcholine is a potent mitogenic mediator is presented (Desai NN et al., Biochem Biophys Res Comm 1991, 481, 361).
For the first time, evidence is reported that aerobic (with elongases-desaturases steps) and anaerobic (polyketide synthase) pathways of fatty acid biosynthesis could operate within a single species, the bacterium Pseudomonas (Wada M et al., J Bacteriol 1989, 171, 4267) .
Prostaglandins were discovered to derive from lipid
precursors through the action of regulated phospholipase A2
(PLA2) (Clark J D et al., Cell 1991, 65, 1043).
Hannun Y and col. proposed a role for the sphingomyelin cycle and for ceramide in regulating cell differentiation (Kim, M -Y et al., J Biol Chem 1991, 266, 484).
Fadok VA et al. discovered the exposure of phosphatidylserine at the lymphocytes outer surface during apoptosis triggering their recognition and removal by macrophages (J Immunol 1992, 148, 2207).
A gene from Arabidopsis that encodes a n-3 desaturase was cloned and an increased production of n-3 fatty acids was obtained by genetic manipulation of the plant (Arondel V et al., Science 1992, 258, 1353).
A novel family of nuclear hormone
receptors controlling the peroxisomal b-oxidation
pathway (PPARs) was described and cloned on Xenopus eggs (Dreyer
C et al., Cell 1992, 68, 879).
Anandamide (arachidonoyl ethanolamine) is discovered in brain tissue and may function as a natural ligand for the cannabinoid receptor (Devane WA et al., Science 1992,258,1946).
Identification of lysophosphatidic acid as the albumin-bound lipid responsible for various cellular messenger properties (Tigyi G et al., J Biol Chem 1992, 267, 21360).
Identification of cyclic phosphatidic acid as a bioactive lipid at the nuclear level (Murakami-Murofushi K et al., J Biol Chem 1992, 267, 21512).
The name bio-diesel was introduced in the USA by the National Soy Diesel Development Board for an alternative diesel fuel made from renewable sources such as vegetable oil and animal fats.
Gottlicher M et al. demonstrated that fatty acids can regulate gene expression mediated by a member of the steroid nuclear receptor superfamily (Gottlicher M et al., PNAS 1992, 89, 4653).
First evidence that the visual development of healthy full-term infants may be vulnerable to the effects of n-3 fatty acid deficiency (Birch EE et al., Invest Ophthalmol Vis Sci 1992, 33, 3242).
An experimental mutant of a plant, Arabidopsis,
deficient in oleic acid desaturase, was shown to be very sensitive to cold
temperature (Miquel M et al., Proc Natl Acad Sci USA 1993, 90, 6208).
Glucose was shown to react with a phospholipid, phosphatidylethanolamine, giving glycosylation end products which are able to enhance free radical formation (Bucala R et al., PNAS 1993, 90, 6434).
Ceramide was shown to be potent agent involved in the programmed cell death (apoptosis) (Obeid LM et al., Science 1993, 259, 1769).
Demonstration of a control of peroxisomal beta-oxidation of fatty acids by fatty acids and retinoids through activation of PPARs (Keller H et al., PNAS 1993, 90, 2160).
Arachidonoylethanolamide is classified as a cannabinoid/anandamide receptor agonist (Felder CC et al., PNAS 1993, 90, 7656).
The CD36 receptor is demonstrated to be involved in binding and transport of long-chain fatty acids in adipocytes (Abumrad NA et al., J Biol Chem 1993, 268, 17665).
Eldred GE et al. proposed a bis-Schiff base structure (N-retinyl-N-retinylidene-ethanolamine) as one of the fluorescent pigments (lipofuscin) of a large number of aged human eyes (Eldred GE et al., Nature 1993, 361, 724). The accumulation of these pigments in retinal epithelium has been linked to retinal degeneration.
First analysis of individual phospholipids
by high-performance capillary electrophoresis (Ingvardsen L et al., JAOCS
1994, 71, 183-188).
In the presence of nitric oxide, novel nitrated fatty acids were shown to be formed under the action of reactive oxidative species (Rubbo H. et al., J Biol Chem 1994, 269, 26066). Nitric oxide may also mediate oxidant-protective reactions in membranes.
For the first time a phosphatidylinositol-specific phosphoinositide 3-kinase from mammalian cells was characterized (Stephens L et al., Curr Biol 1994, 4, 203).
A new vitamin E constituent, a-tocomonoenol,
was discovered in palm oil (Matsumoto
A et al., J Jap Oil Chem Soc 1995, 44, 593).
A monoacylglycerol, 2-arachidonoyl glycerol, has been shown to be anendogenous ligand for cannabinoid receptors in brain tissue (Sugiura T et al., Biochem Biophys Res Comm 1995, 215, 89) and in gut (Mechoulam R et al., Biochem Pharmacol 1995, 50, 83).
Anionic phospholipids (mainly PS and PI) were shown to be the natural ligands of two class B scavenger receptors, SR-BI and CD36 (Rigotti A et al., J Biol Chem 1995, 270, 16221).
EPA and DHA epoxides were shown to inhibit platelet aggregation at concentration below those that affected thromboxane synthesis. It was suggested that the presence of these compounds may contribute to the antiaggregatory effects seen after consumption of n-3 fatty acid-rich diets (VanRollins M et al., J Pharm Exp Ther 1995, 274, 798).
Fatty acid synthase was purified for the first time from a human cell line and its properties and structure were described by the Wakil's group (Jayakumar A. et al., PNAS 1995, 92, 8695).
It has been shown that short chain ceramide-1-phosphate exerts proliferative actions in stimulating DNA synthesis and celle division(Gomez-Munoz A et al., Mol Pharmacol 1995, 47, 883).
Morrow JD et al. discovered isothromboxanes
which are produced by non-enzymatic free radical-catalyzed peroxidation of arachidonoyl
Biol Chem 1996, 271, 23185).
First report of the genetic engineering of plants to modify oil crops (Murphy DJ, Trends Biotechnol 1996, 14, 206).
First demonstration of a modification of proteins (hedgehog signaling proteins) by linking of cholesterol to an amino-terminal signaling domain (Porter JA et al., Science 1996, 274, 255).
Oxysterols derived from cholesterol are involved in the regulation of three important metabolic pathways: steroid hormone biosynthesis, bile acid synthesis, and conversion of lanosterol to cholesterol. Results demonstrate the existence of a nuclear receptor (LXR alpha) signalling pathway for oxysterols (Janowski BA et al., Nature 1996, 383, 728).
Demonstrations of a tight connection between the intensity of blood n-3 fatty acid depletion and the severity of depressive symptoms in patients (Adams PB et al., Lipids 1996, 31, S157; Maes M et al., J Affect Disord 1996, 38, 35)
It was proposed that one of the key factors in human encephalization was increased polyunsaturated fatty acid intake, especially long-chain, n-3 fatty acids from aquatic and terrestrial meat source (Chamberlain JG, Perspect Biol Med 1996, 39, 436).
Kim J.B et al.,. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 1996, 10, 1096).
Rafts are presented as a new aspect
of cell membrane based on the dynamic clustering of sphingolipids and cholesterol.
They were mainly proposed as platform for the attachment of proteins (Simons
K et al., Nature 1997, 387, 569).
Yu M et a. report for the first time a new class of prostaglandins, prostamides, formed from anandamide by cyclooxygenase action (Yu M et al., J Biol Chem 1997, 272, 21181).
Evidence was provided that new oxidation products (F3-Isoprostanes) could be formed in vitro from eicosapentaenoic acid ((Nourooz-Zadeh J et al., Biochem Biophys Res Commun 1997, 236, 467).
A sesquiterpene, methyl farnesoate, is demonstrated to be the crustacean juvenile hormone, synthesized by the mandibular organs (Homola E et al., Comp Biochem Physiol 1997, 117B, 347).
Presqualene diphosphate, a metabolic intermediate between farnesyl diphosphate and squalene, was shown to carry biological activity in human neutrophiles and to serve as a negative intracellular signal preventing superoxide anion generation (Levy BD et al., Nature 1997, 389, 985).
Conjugated fatty acids (CLA) were demonstrated to reduced body fats in mice likely by increasing lipolysis in adipocytes (Park Y et al., Lipids 1997, 32, 853).
Cyclic ADP-ribose was identified as a signaling molecule in the abscissic acid response in plants and was shown to exert its effects by way of calcium (Wu Y et al., Science 1997, 279, 2126).
Demonstration of a specific de novo production of volatile terpenes (mono- and sesquiterpenes) in plants damaged by insect herbivories (Paré PW et al., Plant Physiol 1997, 114, 1161).
A new elicitor of plant volatiles (terpenes), N-(17-hydroxylinolenoyl)-L-glutamine (named volicitin), has been isolated from oral secretions from a caterpillar (Alborn HT et al., Science 1997, 276, 945).
Dinor-oxo-phytodienoic acid, a new hexadecanoid of the jasmonate family, has been discovered as a wound signaling messenger in plants (Weber H. et al., PNAS 1997, 94, 10473).
3-Hydroxypalmitic acid methyl ester was shown to be a volatile autoregulator compound controlling virulence in a phytopathogenic bacterium Ralstonia solanacearum (Flavier AB et al., Mol Microbiol 1997, 26, 251).
PI(3,5)P2 was discovered independently by Brearley C and his colleagues (Biochem J 1997, 323, 597) and by the group of Michell RH (Nature 1997, 390, 187)
Roberts LJ et al. described the oxidative
formation of isoprostane-like compounds (F4-neuroprostanes) in nervous tissues
from docosahexaenoic acid (J
Biol Chem 1998, 273, 13605).
Parchmann S et al. described the formation of new dinor isoprostanes (phytoprostanes) from linolenic acid in plants (Parchmann S et al., J Biol Chem 1998, 273, 32650).
Discovery of a major aminated phospholipid (about 18% of the lipid phosphorus), alanylcardiolipin, in a gram-positive bacteria, Vagococcus fluvialis (Fisher W et al., J Bacteriol 1998, 180, 2950).
First description of lysylcardiolipin in a gram-positive bacteria Listeria welshimeri (Peter-Katainic J et al., J Lipid Res 1998, 39, 2286).
Experiments on tobacco cell culture suggested that N-acetylethanolamine may participate in the early signal transduction events leading to plant defense responses (Chapman KD et al., Plant Physiol 1998, 116, 1163).
Discovery of the role of the peroxisomal proliferator-activated receptor alpha (PPARalpha) in modulating the expression of genes encoding several mitochondrial and peroxisomal fatty acid-catobilzing enzymes (Aoyama T et al., J Biol Chem 1998, 273, 5678).
Discovery of the role of the peroxisomal proliferator-activated receptor gamma (PPARgamma) in adipocyte differentiation (Okuno A et al. J Clin Invest 1998, 101, 1354).
The group of Chatterjee proposed lactosyl ceramide as mediator of activation of cell adhesion through the activation of several transcription pathways (Arai T et al., Circ Res 1998, 82, 540).
Nitrogen dioxide was shown to induce
cis-trans-isomerization of arachidonic acid within cellular phospholipids
generating new compounds termed trans-arachidonic acids (Jiang
H et al., J Biol Chem 1999, 274, 16235).
First rigorous clinical demonstration that n-3 fatty acids from fish oil improved and stabilized mood in patients with bipolar disorder (Stoll AL et al., Arch Gen Psychiatry 1999, 56, 407).
A hypothesis proposed that the relative degree of fatty acid polyunsaturation of membranes can act as a pacemaker of metabolic activity, the increased polyunsaturation being directly related to an increase in cell metabolic activity (Hulbert AJ et al., J theor Biol 1999, 199, 257).
Demonstration that 2-heptyl-3-hydroxy-4-quinolone can function as an intercellular signal (quorum sensing) in Pseudomonas aeruginosa (Pesci EC et al., PNAS 1999, 96, 11229).
For the first time an acylated peptide was discovered : ghrelin is a growth-hormone-releasing peptide of 28 aminno acids in which the serine 3 residue is octanoylated (Kojima M et al., Nature, 1999, 402, 656).
2-arachidonoylglycerol has been shown to be metabolized by cyclooxygenase-2 into
glyceryl prostaglandins (Kozak
KR et al., J Biol Chem 2000, 275, 33744).
The first issue of the journal "European Journal of Lipid Science and Technology" appeared that year.
First experimental evidence that seminolipid, sulfated galactosyl-alkyl-acyl-glycerol is essential for normal spermatogenesis in mice (Fujimoto H et al., J Biol Chem 2000, 275, 22623).
New insect-derived plant regulators stimulating neoplasm formation in plants have been isolated (Doss RP et al., PNAS 2000, 97, 6218). These compounds, named bruchins, are long-chain a,w-diols, esterified at one or both oxygens with 3-hydroxypropanoic acid.
The genomic structure and chromosomal localization of the genes Fads which encode in human the fatty acid desaturases were reported (Marquardt A et al., Genomics 2000, 66, 175).
The Londos group has shown that perilipin A plays a major role in the regulation of triacylglycerol storage and lipolysis in adipocytes (Brasaemle DL et al., J Biol Chem 2000, 275, 38486).
First demonstration of the presence of cholesteryl glucoside in animal cells (Kunimoto S. et al., Cell Stress Chaperones 2000, 5, 3).
phosphatidylethanolamine were shown to recognize coagulation
factor XI and prekallikrein (Sugi T et al., J Autoimmun 2001, 17, 207).
a-Tocomonoenol discovered in 1995 has been shown to provide enhanced antioxidant protection in marine fish adapted to cold-water environments (Yamamoto Y et al., PNAS 2001, 98, 13144).
Identification of a new phosphoinositide in plants, phosphatidylinositol 5-monophosphate which was shown to be accumulated upon osmotic stress (Meijer HJ et al., Biochem J. 2001, 360, 491).
The alkyl monoglyceride, 2-arachidonoylglyceryl ether (noladin ether), was shown to belong to the endocannabinoid family (Hanus L et al., PNAS 2001, 98, 3662).
Abscissic acid was shown to be involved as lipid mediator in the temperature-signaling cascade in sponges (Zocchi E et al., Proc Natl Acad Sci USA 2001, 98, 14859).
Farnesol was determined to be the “quorum-sensing molecule” in a fungus. It was active against a variety of Candida albicans at concentrations between 1 and 50 mM (Hornby J M et al., Appl Environ Microbiol 2001, 67, 2982). This was the first demonstration of an extracellular molecule mediating a quorum-sensing system in eukaryotes.
The vinyl ether bond of plasmalogen phospholipids was demonstrated to be the target of the reactive chlorinating species produced by myeloperoxidase. That attack generates lysoplasmalogens and a 2-chloro-fatty aldehyde (mainly 2-chlorohexadecanal) (Albert CJ et al., J Biol Chem 2001, 276, 23733).
Metz JG et al. have described both in prokaryotes and eukaryotes a novel alternative pathway for the biosynthesis of long-chain polyunsaturated fatty acids. This system does not require the classical sequence of desaturase and elongase enzymes but a polyketide synthase-like gene cluster (Science 2001, 293, 290).
Discovery of a glucose-responsive transcription factor (ChREBP) that modulates the long-term storage of excess carbohydrates as triacylglycerols in adipocytes (Yamashita H et al., PNAS 2001, 98, 9116).
Discovery of new arachidonic acid
peroxidation products, the isofurans, preferentially generated by increased
oxygen tension (Fessel
JP et al., PNAS 2002, 99, 16718).
Discovery of the function of sterol glucoside as primer for the synthesis of cellulose (Peng L et al., Science 2002, 295, 147).
Characterization of a novel family of bioactive fatty acids carrying conjugated triene structures formed formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) termed resolvins which have anti-inflammation effects (Serhan CN et al., J Exp Med 2002, 196, 1025).
Arachidonoyl dopamine was shown to be present in bovine and rat brain and to be agonist of cannabinoid and vanilloid receptors (Huang SM et al., Proc Natl Acad Sci USA 2002, 99, 8400).
Nitrolinoleate, formed from NO-derived reactive nitrogen species and linoleic acid, was shown to inhibit platelet aggregation via cAMP-dependent mechanisms (Coles B et al., J Biol Chem 2002, 277, 5832).
First description of fatty acids and fatty alcohols containing four-membered aliphatic cyclobutane rings in bacteria (order Planctomycetales) capable of anaerobic ammonium oxidation (Sinninghe Damsté JS et al., Nature 2002, 419, 708). They were named ladderane molecules.
Demonstration of the crucial role of the hepatic stearoyl-CoA desaturase in leptin-mediated weight loss in mammals (Cohen P et al., Science 2002, 297, 240).
Observation of a sulfatide deficiency and ceramide elevation in brain tissues in very early Alzheimer's disease (Han X et al., J Neurochem 2002, 82, 809).
Description of tocopherol catabolism via a cytochrome P450 w-hydroxylase pathway shortening progressively the phytyl chain and yielding ultimately the 3'-carboxychromanol excreted in urine (Sontag TJ et al., J Biol Chem 2002, 277, 25290).
A novel class of oxidized phospholipids that serve as high affinity ligands for CD36 and mediate recognition of oxidized forms of LDL by CD36 on macrophages has been identified (Podrez EA et al. , J Biol Chem 2002, 277, 38503).
Lysophospholipase D, which is involved in the production of lysophosphatidic acid, was identified as autotaxin, an enzyme originally found as a tumor cell motility-stimulating factor (Tokumura A et al., J Biol Chem 2002, 277, 39436).
NAD(P)H steroid dehydrogenase-like,
involved in the conversion of lanosterol into cholesterol, may be a new mechanism
for the regulation of the levels and sites of accumulation of intracellular
M et al., Human Mol Gen 2003, 12, 2981).
A new brain messenger, 10,17S-docosatriene formed from docosahexaenoic acid (DHA), is shown to elicit several responses suggesting that it may have a potent neuroprotective effect (Marcheselli VL et al., J Biol Chem 2003, 278, 43807).
Ceramide-1-phosphate was shown to be a specific and potent inducer of arachidonic acid and prostanoid synthesis in cells (Pettus BJ et al., J Biol Chem 2003, 278, 38206)
Specific G protein-coupled receptors
were discovered to be involved in the regulation of lipid and
glucose metabolism, GPR41 and GPR43 receptors activated by propionate and other short
chain carboxylic acids (Brown A J et al., J Biol Chem 2013,278, 11312)
The docosanoid 10,17S-docosatriene,
or neuroprotectin D1, was shown to protect human retinal pigment epithelial
cells from oxidative stress (Mukherjee
PK et al., PNAS 2004, 101, 8491).
Nitrolinoleate, which was previously shown to mediate signaling reactions, was reported to be present in plasma and in red cell membranes representing a large pool of bioactive oxides of nitrogen in the vasculature (Baker PRS et al., PNAS 2004, 101, 11577).
The G2A receptor was shown to mediate T lymphoid cell migration via lysophosphatidylcholine interaction. This function may be relevant to the autoimmune syndrome (Radu CG et al., PNAS 2004, 101, 245).
The phytohormone abscissic acid was reported to be involved as a lipid mediator in connection with cyclic ADP-ribose during hydroid (Cnidaria) regeneration (Puce S et al., J Biol Chem 2004, 279, 39783).
The oxylipin signal jasmonic acid is reported to be activated in plants by an enzyme that conjugates it to isoleucine leading to a conjugate form which is likely the true active jasmonate compound (Staswick PE et al., The Plant Cell 2004, 16, 2117).
11-Methyl-2-dodecenoic acid was determined to be a bacterial cell-cell communication signal (Wang LH et al., Mol Bacteriol 2004, 51, 903). This compound is also active in the regulation of morphology and virulence in a pathogen fungus, Candida albicans.
A butenolide compound present derived from plants and present in smoke was shown to promote seed germination (Flematti GR et al., Science 2004, 305, 977).
Nitrolinoleic acid is shown to be a
potent endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARgamma)
FJ et al., PNAS 2005, 102, 2340).
Fucosylated glycosphingolipids containing polyunsaturated very long chain fatty acids were demonstrated to be essential for spermatogenesis and fertility in mice (Sandhoff R et al., J Biol Chem 2005, 280, 27310).
The germination stimulants, the strigolactones, are demonstrated to derived from the carotenoid pathway (Matusova R et al., Plant Physiol 2005, 139, 920).
The chemical structure of the Caenorhabditis elegans dauer-inducing pheromone is determined as a hydroxylated fatty acid linked to a specific oligosaccharide, ascarylose (Jeong PY et al., Nature 2005, 433, 541).
The selective oxidation of plasmenylcholine by hypochlorous acid, produced by activated phagocytes, leads to the formation of chlorinated derivatives, lysophosphatidylcholine chlorohydrins (Messner MC et al., Chem Phys Lipids 2006, 144, 34).
Retinoic acid coordinates somitogenesis and left-right patterning in vertebrate embryos (Vermot J et al., Nature 2005, 435, 215).
A vitamin A-based chromophore, melanopsin, is the photopigment in the intrinsically photosensitive retinal ganglion cells (Fu Y et al., PNAS 2005, 102, 10339).
2-Hydroxyoleic acid was shown to inhibit cancer cell growth and has antitumor effects in animal models (Martinez J et al., Mol Pharmacol 2005, 67, 531).
The mechanism leading from dietary intake of saturated fats to elevated cholesterol levels was shown to be mediated through PGC-1beta coactivation of the liver sterol responsive element binding protein (SREBP) (Lin J et al., Cell 2005, 120, 261).
Evidence was provided that
F3-isoprostanes are formed in vivo from eicosapentaenoic acid in mice (Gao
L et al., J Biol Chem 2006, 281, 14092).
Dr Endo A was awarded the 22nd Japan Prize for the discovery of the statins (inhibitors of cholesterol biosynthesis) and their development.
It was shown that common genetic variants of the fatty acid desaturase FADS1 and FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in serum phospholipids (Schaeffer et al., Hum Mol Gen 2006, 15, 1745).
Evidence was provided that abscissic
acid is involved in the stimulation of human granulocytes with cyclic ADP-ribose
as second messenger (Bruzzone
S et al., Proc Natl Acad Sci USA 2007, 104, 5759).
Diacyl and plasmalogen phosphatidylethanolamines with the sn-2 position acylated by 15-HETE have been observed in activated platelets and monocytes. These compounds may contribute to lipoxygenase signaling in inflammation (Maskrey BH et al., J Biol Chem 2007, 282, 20151).
First report of a method of mass spectrometric imaging of phospholipids in mouse brain (Hankin JA et al., J Am Soc Mass Spectrom 2007, 18, 1646).
Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Thus, intraventricular administration of propionic acid in rats may provide a means to model some aspects of human autism in rats (MacFabe DF et al., Behav Brain Res. 2007, 10, 176, 149-69).
Discovery of neurofurans,
isodocosanoids derived from docosahexaenoic acid, which may serve as indices of
oxidant stress. They are elevated in brain cortex of animal model of Alzheimer
WL et al., J Biol Chem 2008, 283, 6).
Cyclopentenone isoprostanes (A3/J3-isoprostanes) are produced in vitro and in vivo by the free radical-catalyzed peroxidation of eicosapentaenoic acid. They are likely related to the beneficial effects of fish oil consumption on human health (Brooks JD et al., J Biol Chem 2008, 283, 12043).
Palmitoleate (16:1n-7) was demonstrated to be an adipose tissue-derived hormone (a lipokine) that strongly stimulates in mice muscle insulin action and suppresses hepatosteatosis. Adipose tissue would be able to use lipokines to communicate with distant organs and regulate systemic metabolic homeostasis (Cao H et al., Cell 2008, 134, 933).
Abscissic acid was shown to be a endogenous stimulator of insulin release from human pancreatic b cells with cyclic ADP-ribose as second messenger (Bruzzone S et al., J Biol Chem 2008, 283, 32188).
Long-chain carboxychromanols, metabolites of vitamin E (tocopherols) were shown to be potent inhibitors of cyclooxygenases (Jiang Q et al., PNAS 2008, 105, 20464).
The general structure of oxidized cell membranes with oxidized fatty acids protruding at the aqueous exterior (lipid whisker model) is described (Greenberg ME et al., J Biol Chem 2008, 283, 2385).
Galactolipids containing various poyunsaturated n-3 fatty acids from a marine diatom (Phaeodactylum tricornutum) are able to induce apoptosis in mammalian cells (Andrianasolo EH et al., J Nat Prod 2008, 71, 1197).
A new vitamin E constituent, d-tocomonoenol,
was discovered in Actinidia chinensis fruits (Fiorentino
A et al., Food Chem 2009, 115, 187).
The glycosylphosphatidylinositol anchor (phosphatidyl inositol mannosides) of Mycobacterium tuberculosis was demonstrated to have potent anti-inflammatory activities (Doz E et al., J Biol Chem 2009, 284, 23187). This effect may be one of the strategies developed by mycobacteria to fight against the host immunity.
A nitro-fatty acid (nitro-oleic acid), naturally produced during myocardial ischaemia, was shown to have anti-inflammatory properties and could have therapeutic actions against myocardial ischaemia/reperfusion injury (Rudolph V et al., Cardiovasc Res 2009, cvp275).
The pivotal role of dihydrofolate reductase knockdown in the anticancer activity of 2-hydroxyoleic acid is demonstrated (LLado V et al., PNAS 2009, 106, 13754).
Investigations in animals have shown that the epoxyde derivative of DHA modulates nociceptive signaling associated with pain and inflammation (Morisseau C et al., J Lipid Res 2010, 51, 3481).
A genetic adaptation of fatty-acid metabolism was described in human. A specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids was discovered and its importance in the development of modern pathologies is demonstrated (Ameur A et al., Am J Hum Genet 2012, 90, 809-20).
G protein-coupled receptors GPR41 and GPR43 are activated by propionate and
other short chain carboxylic acids associated with histone acetylation and might
be involved in butyrate-induced inhibitions of
histone acetylation and anti-proliferation (Brown AJ et al., J Biol Chem 2012, 278, 11312-11319).
The microbial metabolites, short-chain fatty acids, regulate the homeostasis of colonic Treg cell that express the transcription factor Foxp3 and are critical for regulating intestinal inflammation (Smith PM et al., Science 2013, 341(6145), 569).
A US expert panel has published a report concluding to an absence of relatioship between dietary cholesterol and prevention of cardiovascular diseases (Adivisory report to the Secretary of Health and Human Services and Secretary of Agriculture, 2015, 215 USDA).
It was determined that short-chain fatty acids, microbiota-derived bacterial fermentation products, regulated brain microglia homeostasis (Erny D et al., Nat Neurosci 2015, 18, 965-77).
Demonstration of a reversible transfer of glucosyl-moieties from glucosylated ceramide to cholesterol and vice versa in mammalian cells (Marques AR et al., J LIpid Res 2016, 57, 451).
Short chain fatty acids and gut microbiota were shown to differ between patients with Parkinson's disease and age-matched controls (Unger MM et al., Parkinsonism Relat Disord 2016, 32, 66).
It was proposed
that gut microbiota produce metabolites, such as SCFAs, that regulate motor
deficits and neuroinflammation in a preclinical model of Parkinson's disease
(Sampson TR et al., Cell 2016, 167, 1469).