COBALAMIN (COENZYME B₁₂): Synthesis and Biological Significance

Abstract

This review examines deoxyadenosylcobalamin (Ado-B12) biosynthesis, transport, use, and uneven distribution among living forms. We describe how genetic analysis of enteric bacteria has contributed to these issues. Two pathways for corrin ring formation have been found-an aerobic pathway (in P. denitrificans) and an anaerobic pathway (in P. shermanii and S. typhimurium)-that differ in the point of cobalt insertion. Analysis of B12 transport in E. coli reveals two systems: one (with two proteins) for the outer membrane, and one (with three proteins) for the inner membrane. To account for the uneven distribution of B12 in living forms, we suggest that the B12 synthetic pathway may have evolved to allow anaerobic fermentation of small molecules in the absence of an external electron acceptor. Later, evolution of the pathway produced siroheme, (allowing use of inorganic electron acceptors), chlorophyll (O2 production), and heme (aerobic respiration). As oxygen became a larger part of the atmosphere, many organisms lost fermentative functions and retained dependence on newer, B12 functions that did not involve fermentation. Paradoxically, Salmonella spp. synthesize B12 only anaerobically but can use B12 (for degradation of ethanolamine and propanediol) only with oxygen. Genetic analysis of the operons for these degradative functions indicate that anaerobic degradation is important. Recent results suggest that B12 can be synthesized and used during anaerobic respiration using tetrathionate (but not nitrate or fumarate) as an electron acceptor. The branch of enteric taxa from which Salmonella spp. and E. coli evolved appears to have lost the ability to synthesize B12 and the ability to use it in propanediol and glycerol degradation. Salmonella spp., but not E. coli, have acquired by horizontal transfer the ability to synthesize B12 and degrade propanediol. The acquired ability to degrade propanediol provides the selective force that maintains B12 synthesis in this group.

Supplementing lactating dairy cows with a vitamin B12 precursor, 5,6-dimethylbenzimidazole, increases the apparent ruminal synthesis of vitamin B12

“…The authors of both studies concurred that, when cobalt supply is adequate, 5,6-DMB availability may become limiting (Gawthorne, 1970b;Rickard et al, 1975), although the metabolic pathway for anaerobic synthesis of 5,6-DMB by ruminal bacteria is not fully elucidated (Renz et al, 1993;Roth et al, 1996). On a weight basis, cobalt represents 4.4% of the CBL molecule, thus, in the present study 0.64 and 0.86 mg of Co were incorporated into CBL for control and 5,6-DMB supplemented diets, respectively.…”

Protein Content of Polyhedral Organelles Involved in Coenzyme B 12 -Dependent Degradation of 1,2-Propanediol in Salmonella enterica Serovar Typhimurium LT2

“…The vitamin B 12 coenzymes adenosyl-B 12 (Ado-B 12 ) and methyl-B 12 ) are required cofactors for at least 15 different enzymes (5,27,30). These enzymes have a broad but uneven distribution among living forms and are vital to human health, are essential to the carbon cycle, and have important industrial applications (5,27,30).…”

“…These enzymes have a broad but uneven distribution among living forms and are vital to human health, are essential to the carbon cycle, and have important industrial applications (5,27,30). Historically, bacteria have provided excellent model systems for the study of vitamins, and recent investigations with several bacterial systems have found the molecular biology of B 12 -dependent processes to be unexpectedly complex (9,27,29,34,35). One of the most surprising findings in this area has been the identification of a polyhedral organelle involved in coenzyme B 12 -dependent 1,2-propanediol (1,2-PD) degradation by Salmonella enterica (9).…”

Genetic and genomic systems to study methylmalonic acidemia

“…Studies on bacterial systems have defined B12 transport, synthetic pathways and enzymatic functions of dependent enzyme systems and have been extensively reviewed in the past [46]. Below, we will focus on uses and potential applications of widely used eukaryotic model organisms.…”