On the Metabolism of Coenzyme B12

Abstract

Since the coenzyme B12 was discovered as an active form of vitamin B12 (B12) by Barker et al. (1), its biochemical propaties including its coenzymic roles, and its metabolism have been studied in many respects.Today it is considered that vitamin B12 in the liver exists in a coenzyme form (2), 5, 6-dimethyl benzimidazolyl cobamide coenzyme (DBCC), which plays an important role in converting methyl malonyl CoA into succinyl CoA in mammalian cells (3,4).On the other hand, studies on the enzymic biosynthesis of DBCC from B12 derivatives were made by Pawelkiwicz et al. (5) and Bernhauer et al. (6), who showed that the extract of Propionibacterium shermanii could catalyze the con version from aquocobalamin to coenzyme B12 in the presence of ATP and Mg. Barker and Brody et al. (7,8) obtained the enzyme for biosynthesis using the same bacterium and searched for the substrate and cofactor necessary for biosyn thesis. Weissbach and Peterkofsky et al. (9-11) succeeded in the biosynthesis of DBCC using the cell-free extract of Clostridium tetanomorphum.On the other hand, Gorna (12) and Pawelkiwicz et al. (13) reported that the homogenate of liver and kidneys could convert cyanocobalamin (CN-B12) into DBCC in vitro. However, only short reports have been made on the conversion process in the body, of which Fenrych (14) used rabbits, and Martson (15) used the sheep.The present author (16) used animal tissues for the study of fractional deter mination of CN-B12, OH-B12, and DBCC and further studied the conversion process leading to DBCC in the liver and kidneys from 57Co-CN-B12 or 57Co-OH-B12 injected intravenously into rats or human subjects. He also examined the conversion pro cess in vitamin B12-deficient state and in the liver injured by carbon tetrachloride and observed how the conversion process was affected by intrinsic factor (IF) known to promote which is the organ uptake of B12.