Hydroxylation of Cholecalciferol

There are two separate cytochrome P450-dependent mixed-function oxidases in the liver that catalyze the 25-hydroxylation of cholecalciferol (see Figure 3.3). The activity of both enzymes is higher in tissue from vitamin D-deficient animals, and there is some evidence that calcitriol either inhibits or represses them. The mitochondrial enzyme (CYP27A), which has a Km of 10-5 M, catalyzes the hydroxylation of cholecalciferol twice as fast ergocalciferol. It also acts on a number of C-27 steroids and is involved in bile acid synthesis. This enzyme requires ferredoxin and ferredoxin reductase for activity. The microsomal enzyme (CYP2D25), with a Km of 10-7 M, only acts on cholecalciferol, and not ergocalciferol, although it also acts on a number of C-27 steroids and will catalyze the 25-hydroxylation of 1a-hydroxycholecalciferol (hydroxycal-ciol) to calcitriol. As discussed in Section 3.4.2, this has been exploited to treat and prevent problems of vitamin D-resistant rickets and osteomalacia in cases of renal failure (renal osteodystrophy) using 1a-hydroxycholecalciferol.

Cholecalciferol Calcitriol

Figure 3.3. Metabolism of calciol to yield calcitriol and 24-hydroxycalcidiol.

Cholecalciferol 25-hydroxylase is not restricted to the liver; kidneys, skin, and gut microsomes also have a cytochrome P450 -dependent enzyme that catalyzes the 25-hydroxylation of cholecalciferol and 1a-hydroxycholecalciferol, but not ergocalciferol. Although there is some evidence that calcitriol can reduce the activity of calciferol 25-hydroxylase, it is not known whether this is physiologically important; the major factor controlling 25-hydroxylation is the rate of uptake of cholecalciferol into the liver. It is the fate of calcidiol in the kidneys that provides the most important regulation of vitamin D metabolism (Wikvall, 2001).

Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.

Get My Free Ebook

Post a comment