title: Stabilisation of methylene radicals by cob(II)alamin in coenzyme B12 dependent mutases.
abstract: Coenzyme B12 initiates radical chemistry in two types of enzymatic reactions, the irreversible eliminases (e.g., diol dehydratases) and the reversible mutases (e.g., methylmalonyl-CoA mutase). Whereas eliminases that use radical generators other than coenzyme B12 are known, no alternative coenzyme B12 independent mutases have been detected for substrates in which a methyl group is reversibly converted to a methylene radical. We predict that such mutases do not exist. However, coenzyme B12 independent pathways have been detected that circumvent the need for glutamate, beta-lysine or methylmalonyl-CoA mutases by proceeding via different intermediates. In humans the methylcitrate cycle, which is ostensibly an alternative to the coenzyme B12 dependent methylmalonyl-CoA pathway for propionate oxidation, is not used because it would interfere with the Krebs cycle and thereby compromise the high-energy requirement of the nervous system. In the diol dehydratases the 5'-deoxyadenosyl radical generated by homolysis of the carbon-cobalt bond of coenzyme B12 moves about 10 A away from the cobalt atom in cob(II)alamin. The substrate and product radicals are generated at a similar distance from cob(II)alamin, which acts solely as spectator of the catalysis. In glutamate and methylmalonyl-CoA mutases the 5'-deoxyadenosyl radical remains within 3-4 A of the cobalt atom, with the substrate and product radicals approximately 3 A further away. It is suggested that cob(II)alamin acts as a conductor by stabilising both the 5'-deoxyadenosyl radical and the product-related methylene radicals.
authors.affiliation: Fachbereich Biologie, Philipps-Universität, 35032 Marburg, Germany. buckel@staff.uni-marburg.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Buckel
authors.forename: Christoph
authors.initials: C
authors.lastname: Kratky
authors.forename: Bernard T
authors.initials: BT
authors.lastname: Golding
mesh_terms: D003038:Cobamides / Q000737:chemistry*; D006801:Humans; D019751:Intramolecular Transferases / Q000737:chemistry*; D008697:Methane / Q000737:chemistry*; D013379:Substrate Specificity; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D003038:Cobamides; C097751:cob(II)alamin; D019751:Intramolecular Transferases; C000913:cobamamide; D008697:Methane; D014805:Vitamin B 12