Vitamin B12
Pernicious anemia was a fatal disease until 1926 when Minot and Murphy demonstrated that treatment with large amounts of liver could reverse the symptoms and prevent recurrence. The cause of the disease was uncovered by Castle and co-workers who demonstrated in 1929 that normal gastric secretion contains an intrinsic factor (If) that is essential for the absorption of the antipernicious anemia principle or extrinsic factor from liver and other animal products. Patients with pernicious anemia lack the gastric IF. The active substance in liver was isolated in 1948 simultaneously by two groups, one in England and the other in the United States. It was found to be identical to the extrinsic factor and the antipernicious anemia principle.
Hodgkin, the 1964 Nobel Prize winner in chemistry, and her co-workers delineated the structural formula of the vitamin. The structure of vitamin B12 was established as an extremely complex nitrogenous compound containing two major portions, the corrin nucleus (which includes cobalt) and the attached nucleotide. Active forms of this vitamin are cyanocobalamin (vitamin BI2), a stable form present in pharmaceutical preparations but not found naturally, hydroxocobalamin (vitamin B 12') aquacobalamin (vitamin B 12b) and nitritocobalamin (vitamin B12C). Cobalt, long known as a trace element essential for some animals, had never before been found in a natural organic compound.
The predominant forms ofvitamin B12 found in blood and other tissues are its two known coenzyme forms,deoxyadenosylcobalamin (adenosylcobalamin) and methylcobalamin, and hydroxocobalamin.Vitamin B12 is remarkably potent. It has a biologic activity 11,000 times that of a standard liver concentrate formerly used in the treatment of pernicious anemia. Consequently, B12 appears to be one of the most potent biologically active substances known. It has been administered therapeutically in doses from 6 to 150 mcg. Comparative results with folic acid in other types of anemia require doses from 20,000 to 50,000 mcg.
