Role of vitamin B12 and folate

Vitamin B12(cobalamin) deficiency associated neuropathy, originally called subacute combined degeneration, is particularly common in the elderly. The potential danger today is that with supplementation with folic acid of diatary staples such as flour, that the incidence of the disease could rise as folic acid, as opposed to natural folate(N5CH3HFGlu1), enters the cell and the metabolic cycle by a cobalamin independent pathway. This describes the clinical presentation of the disease, which unless treated will induce permanent CNS danage. The biochemical basis of the interrelationship between folate and cobalmin is the maintenance of the two function, nucleic acid synthesis and the methylation reactions. The latter is particularly important in the brain and relies especially on maintaining the concentration of s-adenosylmethionine(SAM) which, inturn, maintains the methylation reaction whose inhibition is considered to cause cobalmin deficiency associated neuropathy. SAM mediated methylation reaction are inhibited by its product s-adenosylhomocysteine(SAH). This occurs when cobalmin is deficient and, as a result, methionine synthesis is inhibeted causing a rise of both homocysteine and SAH. Other potential pathogenic processes related to the toxic effect of homocysteine are direct damage to the vascular endothelium and inhibition of N-methyl-D-aspartate receptors.