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

Citation

Miller, William Walter (1968) Part I. Coenzyme B₁₂ as a Hydroformylation-Type Catalyst. Part II. Mechanisms of Hydrogen Transfer in the Methylmalonyl Coenzyme A Mutase Reaction. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/BBKP-QT89. https://resolver.caltech.edu/CaltechTHESIS:12182015-145538579

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.

Thesis Files