Methyl-transfer reactions groups

The cofactor role of the methylcorrinoids is based on enzymatic methyl-group transfer reactions. Formation of a methyl-corrin by the methylation of an enzyme-bound Co -corrin... 

The catalysis of the transfer of a methyl group is an important role of enzyme-bound vitamin B12 derivatives in human, animal, and bacterial metabolism. The known enzyme-controlled methyl group-transfer reactions are key steps in the cobamide-dependent methylations of homocysteine to methionine, in the metabolic formation of methane from other Ci-compounds in methanogenic bacteria, and in the fixation of carbon dioxide via the acetyl coenzyme A pathway of some bacterial autotrophs (Figure 10). ... 

VIII. Methyl Group Transfer Reactions One- versus Two-Step Mechanisms. 404... 

The laboratories of Floss and Arigoni laid the experimental foundation for the stereochemical analysis of methyl group transfer reactions, on the basis of the synthesis from chiral [ H, H, H]acetate of methionine and S-adenosylmeth-ionine carrying a chiral [ H, H, H]methyl group [335, 341), for example. 

Stereochemistry of Enzyme-Catalyzed Methyl Group Transfer Reactions... 

Uric acid that is produced in man is essentially the product of the action of the enzyme xanthine oxidase on xanthine and hypoxanthine. A tiny amount of uric acid may be ingested as part of the diet, but the great bulk is the result of the action of this enzyme on these two purines. These purines are themselves produced either as a result of the breakdown of cellular material in toto, the turnover of nucleic acids in the cells, or as a result of the intermediary metabolism of various purine nucleotide derivatives. These latter compounds are active in the flow of energy, in methyl group transfer reactions, and as part of the functional molecule of many vitamins. There is direct and indirect evidence that some of the uric acid derives from all these sources. Essentially this evidence consists of the demonstration that other parts of the nucleie acids are found in the urine, such as pyrimidine breakdown products (P9) and methylated purines, which are found only in nucleic acids. There is also isotopic evidence that some labeled purines appear in the urine too quickly after administration of radioactive precursors... 

The reverse process, the nucleophile-induced dealkylations of methyl-Co(III)-corrins, has been less studied due to the impediment of the intramolecular coordination of the nucleotide base [134,137]. Indeed, thiolates demethylate methylcobinamide (45) to cob(l)inamide (43) approximately 1000 times faster than MeCbl (3) to B s (40") [137], reflecting the strong stabilizing effect of the coordinated nucleotide in 3 [86,134]. This is of relevance for enzymatic methyl group transfer reactions involving protein bound Co(l)- and methyl-Co(lll)-corrins, where considerable axial base effects are expected [125,138]. 

The catalytically active corrinoids involved in methyl group transfer reactions of these methyl transferases have been characterized as protein-bound Co -corrins (such as cob(I)alamin) and methyl-Co -corrins (such as methyl-cobalamin) with the nucleotide base decoordinated (10,48,49). Recent studies have provided indirect evidence for the methylation of radicals by protein-bound methylcobamides (35), a possible second mechanism of biological methyl transfer... 

Table 8.5 Values of the Br0nsted-type coefbcient a for methyl-group transfer. Reactions in sulpholane at 35 °C X -t- GY XG - - Y with G = CH3. From E.S. Lewis, Ref.

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