The Vitamins 143that accumulates in the skin but not other tissues)
undergoes a non-enzymic reaction on exposure to
UV light, yielding previtamin D, which undergoes a
further reaction over a period of hours to form cho-
lecalciferol, which is absorbed into the bloodstream.
In temperate climates there is a marked seasonal
variation in the plasma concentration of vitamin D;
it is highest at the end of summer and lowest at the
end of winter. Although there may be bright sunlight
in winter, beyond about 40° N or S there is very little
UV radiation of the appropriate wavelength for cho-
lecalciferol synthesis when the sun is low in the sky.
By contrast, in summer, when the sun is more or less
overhead, there is a considerable amount of UV light
even on a moderately cloudy day, and enough can
penetrate thin clothes to result in signifi cant forma-
tion of vitamin D.
In northerly climates, and especially in polluted
industrial cities with little sunlight, people may well
not be exposed to enough UV light to meet their
vitamin D needs, and they will be reliant on the few
dietary sources of the vitamin.
Metabolism to calcitriol
Cholecalciferol, either synthesized in the skin or from
foods, undergoes two hydroxylations to yield the
active metabolite, 1,25-dihydroxyvitamin D or cal-
citriol, as shown in Figure 8.4. Ergocalciferol from
fortifi ed foods undergoes similar hydroxylation to
yield ercalcitriol. The nomenclature of the vitamin D
metabolites is shown in Table 8.3.
The fi rst stage in vitamin D metabolism occurs in
the liver, where it is hydroxylated to form the 25-
hydroxy derivative calcidiol. This is released into the
circulation bound to a vitamin D binding globulin.
There is no tissue storage of vitamin D; plasma cal-
cidiol is the main storage form of the vitamin, and it
is plasma calcidiol that shows the most signifi cant
seasonal variation in temperate climates.
The second stage of vitamin D metabolism occurs
in the kidney, where calcidiol undergoes either 1-
hydroxylation to yield the active metabolite 1,25-
dihydroxyvitamin D (calcitriol) or 24-hydroxylation
to yield an apparently inactive metabolite, 24,25-
dihydroxyvitamin D (24-hydroxycalcidiol). Calcidiol
1-hydroxylase is also found in other tissues that are
capable of forming calcitriol as an autocrine or para-
crine agent.Regulation of vitamin D metabolism
The main function of vitamin D is in the control of
calcium homeostasis and, in turn, vitamin D metabo-
lism in the kidney is regulated, at the level of 1- or
24-hydroxylation, by factors that respond to plasma
concentrations of calcium and phosphate. In tissues
other than the kidney that hydroxylate calcidiol to
calcitriol, the enzyme is not regulated in response to
plasma calcium.Table 8.3 Nomenclature of vitamin D metabolites
Trivial name Recommended name Abbreviation
Vitamin D 3
Cholecalciferol Calciol –
25-Hydroxycholecalciferol Calcidiol 25(OH)D 3
1 α-Hydroxycholecalciferol 1(S)-Hydroxycalciol 1α(OH)D 3
24,25-Dihydroxycholecalciferol 24(R)-Hydroxycalcidiol 24,25(OH) 2 D 3
1,25-Dihydroxycholecalciferol Calcitriol 1,25(OH) 2 D 3
1,24,25-Trihydroxycholecalciferol Calcitetrol 1,24,25(OH) 3 D 3
Vitamin D 2
Ergocalciferol Ercalciol –
25-Hydroxyergocalciferol Ercalcidiol 25(OH)D 2
24,25-Dihydroxyergocalciferol 24(R)-Hydroxyercalcidiol 24,25(OH) 2 D 2
1,25-Dihydroxyergocalciferol Ercalcitriol 1,25(OH) 2 D 2
1,24,25-Trihydroxyergocalciferol Ercalcitetrol 1,24,25(OH) 3 D 2The abbreviations shown in column 3 are not recommended, but are frequently used in the
literature.