Coenzyme B12-dependent Rearrangements Research Articles

The mechanistic and evolutionary basis of stereospecificity for hydrogen transfers in enzyme-catalysed processes

The original of stereospecificity in enzylme-catalysed processes is attributed to either mechanistic imperatives or to the evolutionary origin of an enzyme. Recent analysis of the synanti dichotomy for hydratase–dehydratase enzymes has clearly demonstrated that it is a historical contingency that has played a significant role in determination of stereospecificity. Historical contingencies also appear to play a significant role in (a) the selection of one out of a possible eight different stereochemical courses available for an enoyl thioester reductase, and (b) the discrimination between diastereotopic hydrogens in coenzyme B12-dependent rearrangements.

ω-(Adenosin-5′-O-yl)alkyl)cobalamins Mimicking the Posthomolysis Intermediate of Coenzyme B12-Dependent Rearrangements: Kinetic Investigations on Methylmalonyl-CoA Mutase

Coenzyme-B12 analogues carrying oligomethylene chains (C3-C7) inserted between the central Co atom and the 5′-O atom of the adenosine moiety mimicking the putative posthomolysis intermediate in coenzyme B12-dependent rearrangements were synthesized and examined for their effects on methylmalonyl-CoA mutase from Propionibacterium shermanii. All analogues proved to be inhibitors of methylmalonyl-CoA mutase and in all cases competitive inhibition with respect to coenzyme B12 was found. Inhibition constants (Ki) were determined by two independent methods and showed in both cases the predicted trend: the Ki values versus chain length had minima at the C6 analogue in which the distance is about 10 Å between the central Co atom and the 5′ carbon of the adenosine, assuming a zig-zag chain conformation. This is the postulated distance between the Co and 5′-methylene paramagnetic centers generated in the methylmalonyl-CoA-coenzyme B12 complex after homolytic cleavage of the CoC bond.

ChemInform Abstract: Reactions Related to Coenzyme B12 Dependent Rearrangements: Metal Mediated Free Radical Acyl Migrations in Methyl and Cyclopropyl Substituted Models.

AbstractIn continuation of studies on rearrangements related to B12 catalyzed reactions, novel model compounds are intended to mimic the free radical methylmalonylCoA‐succinylCoA rearrangement.

Reactions related to coenzyme B12 dependent rearrangements: Metal mediated free radical acyl migrations in methyl and cyclopropyl substituted models

Free radicals generated from the methylmalonylcoenzyme A mutase model substrates ( 3) and ( 4) by chromium (II) reduction, or by pyrolysis of the analogous cobaloximes, underwent [1,2]-migration only in the acyl series (R = Ph, Me) and not the critical ester series (R = OEt, SBu). The mechanism of the migration was implied by incorporation into ( 4) of the cyclopropyl ring, the opening of which demostrated the free radical nature of the rearranged intermediate.

1,2-Migrations in free radicals related to coenzyme B12-dependent rearrangements

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,2-Migrations in free radicals related to coenzyme B12-dependent rearrangementsSusan. Wollowitz and Jack. HalpernCite this: J. Am. Chem. Soc. 1988, 110, 10, 3112–3120Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://doi.org/10.1021/ja00218a020RIGHTS & PERMISSIONSArticle Views245Altmetric-Citations60LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

The role of S-adenosylmethionine in the lysine 2,3-aminomutase reaction.

The interconversion of L-lysine and L-3,6-diamino-hexanoate (L-beta-lysine) catalyzed by lysine 2,3-aminomutase is known to be stimulated by added S-adenosylmethionine (Chirpich, T. P., Zappia, V., Costilow, R. N., and Barker, H. A. (1970) J. Biol. Chem. 245, 1778-1789). In this paper we show that enzyme activated by S-[2,8,5'-3H]adenosylmethionine catalyzes the conversion of L-lysine to the equilibrium mixture of L-lysine and L-beta-lysine with incorporation of high levels of tritium into both isomers. The tritium levels in the isomers reflect the equilibrium constant for their interconversion, 84% in the L-beta-lysine and 16% in L-lysine compared with Keq = 5.3 +/- 0.3 in the direction of the formation of L-beta-lysine at pH 7.7 and 30 degrees C. No significant tritium is incorporated into lysine from S-[2,8-3H]adenosylmethionine or S-adenosyl[methyl-3H] methionine under comparable conditions. Therefore, the tritium incorporated into lysine in the former reaction arises from the 5'-position of the 5'-deoxyadenosyl group in S-adenosylmethionine. These experiments implicate the 5'-deoxyadenosyl portion of S-adenosylmethionine in the hydrogen transfer mechanism of this reaction, perhaps in a role analogous to that played by the 5'-deoxyadenosyl moiety of deoxyadenosyl cobalamin in coenzyme B12-dependent rearrangements.

Reactions potentially related to coenzyme B12 dependent rearrangements: observations on the radical [1,2]-acyl and -thiol ester migrations

Reaction of 2-iodomethyl-2-methyl-3-oxo estars with tributyltin radicals, generated, photochemically, from hexabutylditin or tributyltin hydride in cyclohexane, or benzene–acetonitrile, resulted in a [1,2]-acyl migration in 10–63% yields dependent on the source of tin radical and substrate used. Radical migration was confirmed by the use of tributyltin deuteride. Thiol ester group migration was not observed. A new, highly efficient method for thiol ester synthesis is described.

Mechanistic aspects of coenzyme B12-dependent rearrangements. Organometallics as free radical precursors

Abstract

A direct method for cobalt-carbon bond formation in cobalt(3)-containing cobalamins and cobaloximes. Further support for cobalt(3). Complexes in coenzyme B 12 dependent rearrangements.

A direct method for cobalt-carbon bond formation in cobalt(3)-containing cobalamins and cobaloximes. Further support for cobalt(3). Complexes in coenzyme B 12 dependent rearrangements.

Cleavage of Coenzyme B12 by Methylmalonyl Coenzyme A Mutase

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.