Alkyl transfer from quaternary ammonium salts to cobalt (I): Model for the cobalamin-dependent methionine synthase reaction
✍ Scribed by Ellen Hilhorst; Atef S. Iskander; Tjoe B.R.A. Chen; Upendra K. Pandit
- Book ID
- 104203253
- Publisher
- Elsevier Science
- Year
- 1994
- Tongue
- French
- Weight
- 560 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0040-4020
No coin nor oath required. For personal study only.
✦ Synopsis
The reaction of cobaloxime(I) with diverse quatemary ammonium salts Icads, in general, to a group transfer from ainogen to cobalt. The behaviour of the salts in these transalkylation~ is consistent with an SN~ mechanism. involving Co(l) as a nucleophile. In a model study of the cobdamin-dependent methionine syathase reaction, 5-13CH3-methyl l&e&d 5,5,6,7-tetramethyl-5,6,7g-teuahydropteridinium salt (23) -a model of the natural coenzyme 5-cH3Hq-fohxte (l)-was allowed to mact with cobaloxime(l) and cobalamin(l). In each case the formation of the methyl transfer product, namely. methylcobaloxime and methylcobalamia, respectively, was shown by 13c-NMR spectroscQpy. Methionine synthases catalyze the overall methyl transfer from the coenzyme N(5)methyltetrahydrofolate 1 (Scheme 1) to the thiolate of homocysteine 2, to result in the formation of methionine 3 and tetrahydrofolate 4 1. The enzymes found in micro-organisms and mammals utilize cofactor 1 as a reagent and, additionally, require cobalamin as the prosthetic group. The cobalamin or vitamin B12 functions as an intermediate methyl carrier in this biological transmethylation reaction (Scheme I).
The overall transformation catalyzed by cobalamin-dependent methionine synthase consists of two half reactions: (i) transfer of the methyl moiety from the folate coenzyme 1 to the cobalt atom of cobalamin and (ii) donation of the CH3-group of methylc&alamin to the thiol residue of homocysteine (2).
The methyl transfer from methylcobalamin to homocysteine, the second half reaction, has been previously demonstrated2 in absence of the enzyme. It is now generally assumed that a nucleophilic displacement of the methyl moiety of methylcobalamin by the thiolate of homocysteine is involved in the cobalamin-dependent methionine synthe.si~~~~.
To date a nonenzymatic precedent of the first half reaction has been lacking. The displacement of