Vitamin B12 functions as coenzyme for several enzymes of which only two occur in mammalian systems: methylmalonyl-CoA mutase (5'-deoxyadenosylcobalamin as cofactor) and homocysteine methyltransferase (methylcobalamin as cofactor). The former catalyzes the last step in the conversion of propionyl-CoA to succinyl-CoA (the full path is shown on the Biotin page). The reactions catalyzed by these two enzymes are shown below:

It is interesting to note that in the reaction catalyzed by methylmalonyl-CoA mutase the 5'-deoxyadenosylcobalamin prosthetic group forms a free radical upon the homolytic cleavage of the C-Co(III) covalent bond (in most biological cleavage the process occurs via heterolytic cleavage). As a result Co³⁺ is reduced to Co²⁺, then reoxidized in the later stage of the catalytic process with the re-formation of the C-Co bond just after the product, succinyl-CoA is released from the enzyme-cobalamin complex.

Some of the processes in which cobalamin is involved are listed below:

• DNA synthesis in body cells. Especially sensitive to vitamin B12 deficiency are the fast reproducing cells such as those lining the oral cavity, the gastrointestinal, urogenital and bone marrow.
• Erythropoietic cell development and maturation as well as other blood cells involved in defence against pathogens.
• Degradation of fatty acids with an odd number of carbon atoms in some marine organisms. The final round of b-oxidation of these fatty acids yields propionyl-CoA, which is then converted to succinyl-CoA for entry into the citric acid cycle.
• Amino acid metabolism, i.e. the conversion of homocysteine to methionine.
• Secretion of melatonin in the brain. Low levels of melatonin are associated with sleep-wake rhythm disorders.
• Essential for adrenal hormone synthesis, promotion of nerve growth and development as well as mood regulation. Normal B12 levels are associated with feelings of well-being.
• Interactions: Vitamin B12 works with folic acid in biochemical reactions involving methyl group transfers such as in the synthesis of methionine from homocysteine. The buildup of homocysteine in blood plasma may be a factor in the formation of the atherosclerotic plaque. High alcohol and coffee consumption, heavy smoking, low intakes of calcium and iron and liver disease can cause vitamin B12 deficiency.
• Health benefits: Supplementation is useful in conditions like asthma, depression, impaired mental function in the elderly, HIV infection. A recent study showed that 39% of American adults age 26-83 have very low levels of B12 in their blood (1).
• Best food sources: Organ meats (liver, kidney), eggs, fish, cheese.