Linus Pauling Vitamin B-12

Vitamin B12

Vitamin B12 has the largest and most complex chemical structure of all the vitamins. It is unique among vitamins in that it contains a metal ion, cobalt. For this reason cobalamin is the term used to refer to compounds having vitamin B12 activity. Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of vitamin B12 used in the human body (1). The form of cobalamin used in most supplements, cyanocobalamin, is readily converted to 5-deoxyadenosyl and methylcobalamin in the body. In mammals, cobalamin is a cofactor for only two enzymes, methionine synthase and L-methylmalonyl-CoA mutase (2).

Function

Cofactor for methionine synthase

Methylcobalamin is required for the function of the folate-dependent enzyme, methionine synthase. This enzyme is required for the synthesis of the amino acid, methionine, from homocysteine. Methionine in turn is required for the synthesis of S-adenosylmethionine, a methyl group donor used in many biological methylation reactions, including the methylation of a number of sites within DNA and RNA (3). Methylation of DNA may be important in cancer prevention. Inadequate function of methionine synthase can lead to an accumulation of homocysteine, which has been associated with increased risk of cardiovascular diseases (diagram).

Cofactor for L-methylmalonyl-CoA mutase

5-Deoxyadenosylcobalamin is required by the enzyme that catalyzes the conversion of L-methylmalonyl-CoA to succinyl-CoA. This biochemical reaction plays an important role in the production of energy from fats and proteins. Succinyl CoA is also required for the synthesis of hemoglobin, the oxygen carrying pigment in red blood cells (3).

Deficiency

Vitamin B12 deficiency is estimated to affect 10%-15% of individuals over the age of 60 (4). Absorption of vitamin B12 from food requires normal function of the stomach, pancreas, and small intestine. Stomach acid and enzymes free vitamin B12 from food, allowing it to bind to other proteins called R proteins (3). In the alkaline environment of the small intestine, R proteins are degraded by pancreatic enzymes, freeing vitamin B12 to bind to intrinsic factor (IF), a protein secreted by specialized cells in the stomach. Receptors on the surface of the small intestine take up the IF-B12 complex only in the presence of calcium, which is supplied by the pancreas (5). Vitamin B12 can also be absorbed by passive diffusion, but this process is very inefficient—only about 1% absorption of the vitamin B12 dose is absorbed passively (2).

Causes of vitamin B12 deficiency

The most common causes of vitamin B12 deficiency are: 1) an autoimmune condition known as pernicious anemia and 2) food-bound vitamin B12 malabsorption. Although both causes become more common with increasing age, they are separate conditions (4).
More available here: http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/index.html