PROPIONIC ACID METABOLISM: MECHANISM OF THE METHYLMALONYL ISOMERASE REACTION AND THE REDUCTION OF ACRYLYL COENZYME A TO PROPIONYL COENZYME A IN PROPIONIBACTERIA

step is the transfer of a carboxyl group from methylmalonyl CoAl to pyruvate with the formation of oxalacetate and propionyl CoA.2 3 The reaction was found to involve biotin;2 the purified enzyme, methylmalonyl-oxalacetic transcarboxylase, has now been shown to contain this factor.4 Methylmalonyl CoA arises from succinyl CoA by an isomerization the mechanism of which remains obscure. The original proposal that it occurred via a transcarboxylation' was questioned on theoretical grounds as well as by indirect experimental evidenlce.d The discovery that the reaction was dependent on the presence of the various cobamide coenzymes6 suggested that the rearrangement was analogous to the isomerization of glutamic acid to 3-methylaspartic acid observed in Clostridium tetanomorphum.7 In the latter case the rearrangement can be considered to be a cleavage of a propionate moiety with subsequent reattachment of the glycine residue to the a position of propionate. Using an extract of propionibacteria, Eggerer et al.8 showed that the isomerization of methylmalonyl CoA involved a similar migrationl of the formyl thioester group from one methylene position of the propionate moiety to the other. Similar results were obtained in our laboratory with methylmalonyl isomerase isolated from sheep kidneys, as well as from propionibacteria. Eggerer et al.8 suggested that the rearrangement of methylmalonyl CoA involved a free radical intermediate. In accord with this hypothesis, Phares et al.9 recently reported an inhibition of the reaction by chlorpromazine, an efficient electron donor. It has also been suggested" that the reaction might involve a dehydrogenation which would weaken the bond of the formyl CoA group, permitting its translocation to the other side of the double bond. Since there has been no successful demon-