(PHYLLOQUINONE)
The
existence of the vitamin K group was discovered by H. Dam (Biochim.
Zeitschr. 1929, 215, 475) in studying cholesterol metabolism in chicks. He noted a new
deficiency syndrome in the young birds fed a fat deficient diet. The characteristic
features were a lengthened blood clotting time, anemia and hemorrhage. Ten years later,
E.A. Doisy's
group (Binkley et al., J. Biol. Chem. 1939, 130, 219) succeeded in isolating the vitamin
from hexane extracts. Although at the time the structure had not been established,
chemical and physical properties were correctly attributed to a substituted
1,4-naphthoquinone. Subsequent works by H. Dam, rewarded with the
Nobel prize for medicine in 1943
"for his discovery of vitamin K", with E.A. Doisy "for his
discovery of the chemical nature of vitamin K", led to the characterization of the
molecule he termed vitamin K (Koagulationsvitamin).
Vitamin K1 was named phylloquinone since it is an indirect product of photosynthesis in
plant leaves where it occurs in chloroplasts and participates in the overall
photosynthetic process. The methyl naphthoquinone ring has a phytyl side chain (partially saturated
polyisoprenoid alcohol).
Vitamin K (its reduced form) is necessary for
post-translational modification of coagulation factors II (prothrombin), VII, IX and X in
the liver. In the presence of the reduced form of vitamin K (dihydro vit K or vitamin K
hydroquinone) formed by the action of a reductase enzyme on phylloquinone, certain
glutamic acid residues of the nascent polypeptides are converted to g-carboxyglutamic
acid by a carboxylase enzyme. This confers the ability to bind calcium, a property
essential for the physiological function of these proteins. During the reaction, a
molecule of vitamin K epoxide (vit K 2,3-oxide) is formed which is further reduced, mainly
by cellular thiol reagents, back to vitamin K1 (phylloquinone).
Vitamin
K1 (MW: 450.7) is a yellow viscous oil with a maximum absorbance at 248 nm (molar abs
coeff.:19900, the same for menaquinones), soluble in ethanol, hexane, chloroform and
vegetable oils. Vit K1 is sensitive to sunlight (destroyed after one hour), unaffected by
diluted acids but destroyed by basic solution and transformed by reducing
agents. Vitamin K1
oxide (MW: 466.7) is much more stable to light and soluble in the same solvents as Vitamin
K1. It has a maximum absorbance at 259 nm (molar abs. coeff.: 6170).
The K vitamins are subject to side-chain structural isomerization, and naturally
occurring K1 is found exclusively as the biologically active 2'-trans-isomer.
However, biological samples may contain some quantities of the inactive cis-isomer.
Thus, its amount must be estimated in establishing reliable food databases.
Phylloquinone is abundant in green vegetables (peas : 0.4,
lettuce and asparagus : 1, Brussel sprout : 1.8, brocoli : 2.4, spinach
: 5, kale : 8 µg/g), some oils (sunflower : 0.1, olive : 0.8, soybean :
2.4 µg/g) but poorly represented
in fruits (1 to 30 ng/g) except avocado (400 ng/g) and kiwi (250 ng/g). Grain products
have also very low levels of vitamin K1 (1 to 70 ng/g) . Animal products including eggs do
not appear to contain appreciable amounts of vitamin K1 (less than 50 ng/g) and less than
10 ng/g are found in fish and shellfish. High amounts are found in butter (up to 1 µg/g)
but lower amounts in cheese (20-100 ng/g). In contrast, a high diversity of menaquinones
are present in dairy products.
A provisional table can be found in the work of Booth SL et al. (J Food Comp Anal 1993, 6,
109).
In animal tissues, phylloquinone is distributed in liver but also in heart, but
is present at low concentrations in brain (Thijssen
H et al., J Nutr 1996, 126, 537).
An adequate intake for a 25-year old male for Vitamin K is about 120
micrograms/day.
VITAMIN K2
(MENAQUINONES)
A second vitamin K (vit K2) was isolated very early from putrified fish meal as a product of microbial synthesis (McRee RW et al., J. Am. Chem. Soc. 1939, 61, 1295). It has the same absorption peaks in UV region as vit K1 but with a slightly lower intensity (molar abs. coeff. at 248 nm: 11800). Vitamin K2 has a poly-isoprenoid unsaturated side-chain of various length, with isoprene units varying from 4 to 13. These compounds are called menaquinones-n or MK-n.
As an example of the various menaquinone forms, MK-7 has 6+1=7 isoprenoid units or 35
carbons in the side chain and can be called vitamin K2(35) or menaquinone-7. This could be
called also 2-methyl-3-all-trans-farnesyl digeranyl-1,4-naphthoquinone. Farnesol and geraniol are the alcohols with 3
(15 carbons) and 2 (10 carbons) isoprenoid units, respectively. One of the first
menaquinones discovered was MK-6 (Isler, 1958) which can be called
2-methyl-difarnesyl-1,4-naphthoquinone. Most menaquinone-containing organisms contain a
series of menaquinones, the major homologs with n=6 to 9 constituting about 90% of the
total.
Among human foods, dairy products are particularly rich in menaquinone species. As an
example, a common cheese (Camembert) contains about 40 ng/g of vitamin K1 but about 600
ng/g of menaquinones (less than 2% MK5, MK6 and MK7, 9% MK4, 27% MK8 and 62% MK9).
In animal tissues, menaquinones (mainly MK-4) are present at concentrations
exceeding those of phylloquinone in pancreas, salivary gland and brain (Thijssen
H et al., J Nutr 1996, 126, 537). MK-4 accumulation in nonhepatic organs
was shown to result from a synthesis rather than an uptake from the gut. MK-4
concentration (about 80 times that of phylloquinone) was shown to be correlated
with sphingolipid concentrations in rat brain (Carrie
I et al., J Nutr 2004, 134, 167). That association suggests a role of
that menaquinone in the brain function since the vitamin K status has been shown
to influence the brain sulfatide metabolism in young mice and rats (Sundaram
KS et al., J Nutr 1996, 126, 2746).
It was shown by oral administration to vitamin K-deficient chicks that isoprenologs with 3
to 5 isoprenoid groups in either menaquinone or phylloquinone type compounds have maximum
biological activity.
2-methyl-1,4-naphthoquinone
or menadione is called also vitamin K3. It has the same physiological activity in vivo as
phylloquinone by alkylation in position 2 with an isoprenoid chain in the liver. As it is
a lipid soluble molecule, its activity depends on the presence of lipids in the diet to
promote absorption. Menadione sodium bisulfite complex is water soluble and thus is used
as food additive in vitamin mix for animals.
