Part I. Coenzyme B₁₂ as a Hydroformylation-Type Catalyst. Part II. Mechanisms of Hydrogen Transfer in the Methylmalonyl Coenzyme A Mutase Reaction

Author: Miller, William Walter

Year: 1968

Degree: Dissertation (Ph.D.)

Advisor: Richards, John H.

Committee Member: Unknown, Unknown

Option: Chemistry

DOI: 10.7907/BBKP-QT89

Abstract

Part I

The mechanism of the hydroformylation reaction was studied. Using cobalt deuterotetracarbonyl and 1-pentene as substrates, the first step in the reaction, addition of cobalt tetracarbonyl to an olefin, was shown to be reversible.

Part II

The role of coenzyme B12 in the isomerization of methylmalonyl coenzyme A to succinyl coenzyme A by methylmalonyl coenzyme A mutase was studied. The reaction was allowed to proceed to partial completion using a mixture of methylmalonyl coenzyme A and 4, 4, 4-tri-2H-methylmalonyl coenzyme A as substrate. The deuterium distribution in the product, succinyl coenzyme A, was shown to best fit a model in which hydrogen is transferred from C-4 of methylmalonyl coenzyme A to C-5’ of the adenosyl moiety of coenzyme B12 in the rate determining step. The three hydrogens at the 5’-adenosyl position of the coenzyme B12 intermediate are then able to become enzymatically equivalent before hydrogen is transferred from the coenzyme B12 intermediate to form succinyl coenzyme A.

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