VITAMIN D
The Nobel Nobel prize
for chemistry for 1928 was awarded to Adolf
Windaus "for his studies on the constitution of the sterols and
their connection with vitamins". The vitamin in question was vitamin D
and Windaus was the first scientist to receive an award mentioning vitamins.
A comprehensive review of the vitamin D history viewed through the contribution
of Windaus may be found in a paper by Wolf G (J Nutr 2004, 134, 1299).
Vitamin D2 (calciferol)
originates from irradiation at about 260nm of ergosterol
while vitamin D3 is formed by irradiation of a provitamin molecule (7-dehydrocholesterol) present in the skin and
gut lining. Vitamin D3 was isolated around 1936 (Brockmann) from the very potent liver oil
of the tuna fish. The unsaponifiable fraction was partitioned between 90% methanol and
petroleum ether to separate vitamins A and D. The residue from the petroleum phase
contained vitamin D3 to be purified by multiple chromatography. The total synthesis was
done around 1952 (Woodward, J Amer Chem Soc, 74, 4223). When tested on rats, the two
vitamins are equally potent (vitamin D3 is more active than D2 in the chick test). The
international unit has been so defined as 40 i.u./µg. Natural fish liver oils vary from
about 100 i.u./g in cod to 200,000 i.u./g in tuna fish.
DeLuca HF
(Holick M F et al., Biochemistry 1971, 10, 2799), Norman AW (Biochem
Biophys Res Commun 1971, 42, 1082), and Kodicek E (Fraser DR et
al., Nature 1970, Nature 228, 764) independently reported the
existence of an active metabolite, 1,25-dihydroxyvitamin D3, which was produced
in the kidneys. From these observations it was surmised that vitamin D3 was
hydroxylated in the liver to become 25-hydroxyvitamin D3, the major circulating
form of the vitamin, and then converted to 1,25-dihydroxyvitamin D3 in the
kidneys. Thus, this final metabolic product is now considered as the
metabolically active form of vitamin D3, which carried out its functions in
initiating intestinal calcium transport.
Initially, the determination of vitamin D was based on a reaction between antimony
trichloride giving a yellow color with l max 500nm.Removal of vitamin A and E was
necessary. Partition chromatography is actually used with success.
vitamin D2 |
Vitamin D3 |
|
| Molecular weight | 396.6 |
384.6 |
| l max | 265 |
265 |
| Molar extinction coefficient | 18,200 |
18,200 |
| m.p. | 116°C |
83°C |
For humans, the requirements are about 100
i.u./day for a man but 400 i.u./day for a child or a pregnant woman.
