Functions of vitamin B12
Each of the vitamin Bl2 coenzythylmalonyl CoA), and of odd chain fatty acids (propionyl CoA). Oxidation of succinyl CoA in the citric acid cycle permits their complete oxidation to CO2 (propionyl CoA methyl malonyl CoA succinyl CoA CAC), thereby involving vitamin B12 in intermediary metabolism.
Although the role of vitamin B12 in the methylmalonate-succinate conversion has been linked to the function ofthis vitamin in the nervous system, the exact biochemical defect that causes the neural damage in B12 deficiency remains unknown. Myelin synthesis appears to be impaired, resulting in insidious degeneration of peripheral and central nervous systems, usually starting with the former. The presence of high concentrations of odd carbon number straight and branched chain fatty acids (C15 and C17) and their increased synthesis from propionic acid has been demonstrated in nerve samples from pernicious anemia patients.
Methylmalonic acid is barely detectable in the urine of healthy people, but it is excreted in large amounts in vitamin B12 deficiency and by people with inherited methylmalonic aciduria. More than one mutation apparently can cause this condition, and only some respond to large doses of vi tamin B 12 Defective synthesis of adenosylcobalamin is suspected to be the cause in the responsive cases. A combined homocystinuria and methylmalonic aciduria also exists and is believed to involve defective synthesis of both B12 coenzymes.
Utilization of other amino acids also may be altered in vitamin B12 deficiency (reduced protein synthesis related to DNA levels), resulting in the elevation of several amino acids in blood and urine. Increased availability of tyrosine is suspected as a cause of hyperpigmentation (increased melanin synthesis from tyrosine) in some patients with pernicious anemia or folate deficiency. In pernicious anemia, decreased inhibition of tyrosinase by reduced levels of glutathione (GSH) may also contribute to the increased production of melanin.
