ABSTRACT
There are two vitamin B12 coenzymes with known metabolic activity in humans, namely methylcobalamin and adenosylcobalamin.
Vitamin B12 deficiency has a drastic effect on folate metabolism because methylcobalamin is a coenzyme for methionine synthetase, the enzyme that catalyzes the methylation of homocysteine to methionine using 5-methyl-tetrahydrofolate (5-methyl-THF) as the methyl donor. The inability to synthesize methionine from homocysteine in the absence of vitamin B12 means that THF cannot be regenerated from the demethylation of 5-methyl-THF. The folate thus becomes trapped in the form of 5-methyl-THF because the formation of this derivative by reduction of 5,10-methylene-THF is thermodynamically irreversible. This situation could lead to the inability to form the other THF derivatives that are necessary for purine and pyrimidine synthesis. The consequent lack of DNA synthesis causes many hemopoietic cells to die in the bone marrow. In this event, a megaloblastic anemia that is clinically indistinguishable from that induced by folate deficiency results. When this type of anemia is caused by deficiency of vitamin B12, it is called pernicious anemia, because it is accompanied by a neuropathy which is unrelated to folate deficiency. The neuropathy is caused by the inability to produce the lipid component of myelin, which results in a generalized demyelinization of nerve tissue. Neuropathy begins in the peripheral nerves, affecting first the feet and fingers, and then progressing to the spinal cord and brain.
