8.2.8.10 Vitamin D (Calciferol)
Vitamin D (8.57, calciferol) is found in fish-liver oils and milk. It is also produced in
human skin from a steroid previtamin by sunlight. Ergosterol is another previtamin D
compound and undergoes photo-rearrangement to vitamin D 2 , whereas cholesterol and
cholesterol derivatives produce vitamin D 3. The two vitamins have the same activity in
humans. These photo-rearrangements, resulting in the cleavage of the steroid B ring, are
used industrially to manufacture these vitamins.
The active forms of the D vitamins are lα,25-dihydroxy-vitamin D 3 and 25-hydroxy-
vitamin D 3. They are formed by enzymatic hydroxylation in the liver microsomes and
then in the kidney mitochondria by a ferredoxin flavoprotein and cytochrome P-450. The
1,25-dihydroxy vitamin is then transported to the bone, intestine, and other target organs
(kidneys, parathyroid gland). Consequently, it can be considered a hormone since it is
produced in one organ but used elsewhere. It mobilizes calcium and phosphate and also
influences the absorption of these ions in the intestine, thus promoting bone mineraliza-
tion. The hormone is also active in relieving hypoparathyroidism and postmenopausal
osteoporosis, which, for example, results in the brittle bones of elderly women.
Overall calcium metabolism is regulated by the parathyroid gland (parathormone) and
the thyroid hormone calcitonin. Parathormone regulates the synthesis of 1,25-(OH) 2 D 3 ,
which manages bone and kidney calcium metabolism as well as promoting Ca^2 +intake
in the gut. The role of calcitonin is less clear, although it works against parathormone.
Serum calcium represses parathormone synthesis, completing a feedback loop.
Vitamin D deficiency, known as rickets,was described in children as early as 1645
by Webster, in “gloomy, sunless England.” Women wearing extensive black veils also
can show osteoporosis, since they are not exposed to sunshine at all. In many Western
countries, milk is fortified with about 400 units of vitamin D 3 (10μg/liter), the mini-
mum daily requirement for children or adults. Therefore, with a proper diet and sun-
shine, rickets should not occur in children. Pregnant women have a higher requirement,
but overdosage of the vitamin leads to toxic symptoms. Although rickets is not a current
clinical problem, osteoporosis (“thinning of the bones”) has emerged as a very relevant
clinical problem, especially in older women.
510 MEDICINAL CHEMISTRY