Antipernicious anemia factor

Vitamin B12 (1) was discovered some 55 years ago as the (extrinsic) antipernicious anemia factor, important for human and animal metabolism. The cobalt complex (1) was structurally characterized by X-ray analysis in the laboratory of D.C. Hodgkin.In these studies, the unique buildup of the tetrapyrrolic corrin ligand and the intramolecularly coordinating pseudo-nucleotide function of the vitamin were discovered. ... 

Antipernicious anemia factor, vitamin Bis and, VIII, 11 Antipneumonia factor, VII, 212 Antistiffness factor, VII, 211, 212 assay, VIII, 116-117 bacterial metabolism and, VIII, 116 deficiency,... 

Nearly 60 years ago, the red cyanide-containing cobalt-complex vitamin Bi2 (1. cyanocob(III)alamin, CNCbl) was discovered and isolated as the (extrinsic) antipernicious anemia factor [2,3]. Vitamin Bn (1, CNCbl) crystal-Uzes readily and is a relatively inert Co(III)-complex. It is the most important... 

Early studies for the purification of the antipernicious anemia factor used either minced liver preparations or proteolyzed liver extracts in which the concentration of the factor was of the order of one part per million. Adsorption chromatography, partition chromatography, and extraction were the methods of choice for purification. In the initial fractionation steps, the factor was adsorbed on either activated carbon or fuller s earth, and eluted with either aqueous ethanol, phenol, or p3U-idine. Intermediate purification steps were accomplished by partition chromatography adsorption chromatography on either silica or alumina was also effective. At various stages of these column procedures, the activity could be removed from aqueous solution by butanol extraction or with phenol or cresol in combination with solvents such as butanol or toluene. Final purification was usually accomplished by crystallization from aqueous acetone solution. 

There are suggestions in the literature that, in addition to ascorbic acid, pteroylglutamic acid, the antipernicious anemia factors, and the adrenal cortex may play a role in tyrosine oxidation in the animal body. The evidence for this is that liver homogenates from rats deficient in pteroylglutamic acid were unable to oxidize tyrosine at a... 

The presence of the benzimidazole system in a natural product is most striking in the case of vitamin Bu (cyanocobalamin). It was isolated from liver extracts and from the fungus Streptomyces griseus. It is an antipernicious anemia factor. Elucidation of its complex structure was achieved by X-ray analysis (Crawfoot-Hodgkin, 1957). 5,6-Dimethylbenzimidazole is bonded via the atom N-1 to D-ribose as an N-glycoside N-3 is linked to a cobalt ion which is situated in the center ofa corrin system (cf. p. 557). 

Cyanocobalamin (35) (vitamin B12) was isolated from liver extract and from Streptomyces griseus. It is of great importance as the antipernicious anemia factor. Its complex chemical structure was elucidated by X-ray investigation (Crowfoot-Hodgkin, 1957). Its central unit is a cobalt complex of a highly substituted corrin system (see p. 551). The total synthesis of vitamin B12 was achieved by Eschenmooser and Woodward in 1971 [28]. 

EL Smith. Purification of antipernicious anemia factors from liver. Nature 161 638-639, 1948. 

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