Lipid-Soluble Vitamins

The four lipid-soluble vitamins - A,D,E, and K - are made from the same 5-carbon building blocks (dimethylallyl pyrophosphate and isopentenyl pyrophosphate) as the steroids. Although one of these, Vitamin D, is ultimately derived from cholesterol, the other three are not.

> Vitamin A - also called all-trans-retinol, is an isoprenoid alcohol that plays a key role in vision and a role in controlling animal growth. Vitamin A must either be present in the diet, or derived from -carotene, an isoprenoid compound prominent in carrots. See Figure 19.25 for the biosynthesis of all-trans-retinol. Dehydrogenation of retinol yields the aldehyde, retinal, which has a role in vision. Another derivative of retinol is retinoic acid, which can be made by the oxidation of retinal.

> Retinoids (derivatives of retinol) act like steroid hormones and interact with specific receptor proteins in the cell nucleus. The ligand-receptor complexes bind to specific DNA sequences, where they control the transcription of particular genes.

> Vitamin D - the most abundant form is D 3, also called cholecalciferol. Vitamin D is not technically a vitamin, because it is not required in the diet. It arises from UV-photolysis of 7-dehydrocholesterol, an intermediate in cholesterol biosynthesis (see here).

> Vitamin D regulates calcium and phosphorus metabolism, particularly the synthesis of the inorganic matrix of bone, which consists largely of calcium phosphate.

> D 3 undergoes two successive hydroxylations catalyzed by mixed-function oxidases. The first occurs at carbon 25 in liver. When calcium levels are low, hydroxylation occurs at carbon 1, yielding the active form, 1,25(OH)D 3, which stimulates osteoblasts to take up calcium. In the intestine, 1,25(OH)D 3 stimulates transcription of a protein that stimulates calcium absorption into the bloodstream. When calcium levels are adequate, hydroxylation occurs instead at carbon 24, yielding the inactive 24,25(OH)D 3 form.

> Vitamin E - also called -tocopherol. Vitamin E is an antioxidant. It is particularly effective in preventing the attack of peroxides on unsatured fatty acids in membrane lipids. Deficiency of vitamin E also leads to other symptoms, however, so vitamin E probably plays other roles as yet undiscovered.

> Vitamin K - found in plants as phylloquinone (vitamin K 1) and in animals as menaquinone (vitamin K 2). Vitamin K 2 is essential for the carboxylation of glutamate residues in certain proteins, to give -carboxyglutamate. This modification allows the protein to bind calcium, an essential event in the blood clotting cascade. Carboxylation of glutamate is also important in other proteins involved in the mobilization or transport of calcium.

See also: Steroid Metabolism, Dimethylallyl Pyrophosphate, Isopentenyl Pyrophosphate, Cholesterol Biosynthesis, Chemistry of Photoreception

INTERNET LINKS:

1. Retinol Metabolism

2. Vitamin K

3. Vitamin D 3