Vitamin D Biochemistry

Vitamin D exists in two forms, vitamin D2 and vitamin D3, which differ in the structure of their side chains. These are called ergocalciferol and cholecalciferol respectively. Both forms are equivalent as to their biological activity and equivalent in dosage. Both are metabolized by conversion to the 25-hydroxy form and then to the 1,25-dihydroxy metabolite in the kidney, which is the bioactive form. This has a structure which is similar to other steroid hormones produced in the body.

Vitamin D2 is found in a few plant sources, but is mostly produced on a commercial scale by the irradiation of yeast. This is the form used to fortify foods and to produce supplements. Vitamin D3 has several sources, being produced by ultraviolet radiation acting on the parent compound, or ingested in the form of deep sea fatty fish, egg yolks or liver, or supplements.

Vitamin D is a derivative of 7-dehydrocholesterol, also called ergosterol. This conversion is mediated by the action of ultraviolet radiation the parent compound, which is formed in the Malpighian layer of skin during a relatively minor route of cholesterol synthesis. Ultraviolet radiation with wavelengths between 290-315 nm causes the bond between the 9th and 10th position of the steroid ring to open, forming a compound called secosterol. This further undergoes cis-to-trans isomerization, by the formation of a trans bond between the 5th and 6th carbon atoms, leading to the formation of vitamin D3, or cholecalciferol. The involvement of ultraviolet radiation in the process has led to vitamin D being nicknamed the “sunshine vitamin.”
 

Cholecalciferol is then carried to the liver, where a mitochondrial hydroxylase enzyme introduces a hydroxyl group at the 25 position. This reaction requires both energy in the form of NADPH and oxygen. The product, called 25-hydroxy cholecalciferol, is the inactive storage form of cholecalciferol, and is stored in the liver.

In case of need, 25-hydroxycholecalciferol is transported to the kidney where a second hydroxylation occurs at the 1 position, converting it to 1,25-dihydroxy cholecalciferol, the bioactive form of vitamin D. The production of this active form is regulated by an enzyme produced in the kidney, which is itself controlled by several factors. These include feedback from the level of the active form of the vitamin already in circulation, the secretion of parathyroid hormone, as well as calcium and phosphate levels which are the primary target of action of the vitamin.

1,25-dihydroxy cholecalciferol, also called calcitriol, is carried in the bloodstream to the intestinal mucosa. There it stimulates the absorption of calcium and phosphate, the mineral ions which are of prime importance in the building up of bone and other supportive tissue. It also promotes bone growth and remodeling by osteoblasts and osteoclasts.

References

• Vasudevan, D. M., Sreekumari, S., & Vaidyanathan, K. (2013). Textbook of biochemistry for medical students (7th ed.). New Delhi, India: Jaypee Brothers Medical Publishers.
• http://dwb.unl.edu/teacher/nsf/c10/c10links/georgia.ncl.ac.uk/vitamind/VitDBioch.html
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012634/
• http://www.cnpp.usda.gov/sites/default/files/dietary_guidelines_for_americans/Vitamins-AAPVitaminDReport.pdf