Brain function in the elderly: 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 dietary staples such as flour, that the incidence of this 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 chapter briefly describes the clinical presentation of the disease, which unless treated will induce permanent CNS damage. The biochemical basis of the interrelationship between folate and cobalamin is the maintenance of two functions, 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, in turn, maintains the methylation reactions whose inhibition is considered to cause cobalamin deficiency associated neuropathy. SAM mediated methylation reactions are inhibited by its product S-adenosylhomocysteine (SAH). This occurs when cobalamin is deficient and, as a result, methionine synthase is inhibited causing a rise of both homocysteine and SAH. Other potential pathogenic processes related to the toxic effects of homocysteine are direct damage to the vascular endothelium and inhibition of N-methyl-D-aspartate receptors.
Weir
D G
DG
Department of Clinical Medicine, Trinity College, Dublin, Ireland.
Scott
J M
JM
D000368:Aged; D004247:DNA / Q000096:biosynthesis; D005492:Folic Acid / Q000502:physiology; D005494:Folic Acid Deficiency / Q000150:complications* / Q000378:metabolism; D006801:Humans; D008745:Methylation; D009422:Nervous System Diseases / Q000209:etiology* / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D014805:Vitamin B 12 / Q000502:physiology; D014806:Vitamin B 12 Deficiency / Q000150:complications* / Q000378:metabolism
D012436:S-Adenosylmethionine; D004247:DNA; D005492:Folic Acid; D014805:Vitamin B 12