Biochemistry of Vitamin D

The following exegesis is my own understanding of the natural production of Vitamin D. Other interpretations are also available on the net, notably at the University of California, Riverside Vitamin D Biochemistry site.

Provitamin D is a simple derivative of cholesterol, which occurs when a hydrogen is removed from the number 7 carbon, which then forms a double bond with the number 8 carbon, in the second, or 'B' ring of the cholesterol molecule. The cholesterol is 'oxidized' (that is, an electron is removed with the hydrogen atom), so that the double bond is a consequence of 2 mutually shared electrons between carbons 7 and 8.

 

 

Provitamin D is converted to Vitamin D3by the action of ultraviolet light through our skin. In this reaction, the B ring of the sterol molecule is opened.

 

Cholecalciferol, that is, Vitamin D3 is transported to the liver. Here an enzyme, loosely referred to as 'mitochondrial hydroxylase', introduces an hydroxyl (OH) group at position 25. This reaction requires energy in the form of NADPH, and the presence of molecular oxygen. This new important intermediate, known as 25 - hydroxycholecalciferol, is not the active form of the vitamin, but is stored in the liver if there is already sufficient active vitamin D in the body.

 

 

When more active vitamin is required, the 25 - OH compound is transported to the kidney where a new hydrolase enzyme is synthesized. This enzyme introduces another hydroxyl group at position 1, and the bioactive form of Vitamin D is produced. This 1-hydroxylase enzyme is controlled by parathyroid hormone (PTH), and by calcium and phosphate concentrations in the blood, as well as by feedback regulation from the active form of the vitamin.

 

 

Calcitriol (1,25 - dihydroxycholecalciferol) is the biologically active form of Vitamin D, and it is transported in the bloodstream to its major site of action in the mucosal cells of the intestine, where calcium and phosphate absorption is stimulated. These cells also contain a cytoplasmic calcium-binding protein, whose synthesis is induced by calcitriol. This protein is important in calcium storage, and can also be found in kidney tubule cells, where it may minimise loss of calcium to the urine.

 

Rickets and Vitamin D

Larry Winger

Clinical Biochemistry