Cleavage of Coenzyme B12 by Methylmalonyl Coenzyme A Mutase
Year: 1973
Type: article
Abstract: Methylmalonyl-CoA mutase-dependent cleavage of coenzyme B12 took place in the presence of succinyl-CoA, one of the substrates of the enzyme, and in the presence of malonyl-CoA, a competitive inhibitor (Ki 0.12 mm). Other competitive inhibitors of the reaction, including acetyl-CoA, propionyl-CoA, glutaryl-CoA, and CoA itself, did not replace malonyl-CoA in this cleavage reaction. With both succinyl-CoA and malonyl-CoA, the cleavage of coenzyme was progressive with time, without evidence for an initial burst. The cleavage reaction did not depend on oxygen, since it occurred under anaerobic as well as aerobic conditions. The adenosyl derivative formed by the cleavage of 5'-deoxyadenosylcobalamin in the presence of each of the CoA esters was identified chromatographically as 5'-deoxyadenosine. Malonyl-CoA did not appear to be chemically altered during the course of the reaction; experimental difficulties precluded a similar investigation of the fate of succinyl-CoA. These experiments have shown that under certain circumstances, methylmalonyl-CoA mutase is able to cleave the carbon-cobalt bond of coenzyme B12 with the production of 5'-deoxyadenosine. The findings are consistent with the view that the currently proposed mechanism of coenzyme B12-dependent rearrangements, which involves cleavage of the carbon-cobalt bond followed by abstraction of a substrate hydrogen atom to form 5'-deoxyadenosine, may be generally valid for all reactions of this class.
Source: Journal of Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1538488473