Biochemistry - The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Coenzymes: specialized natural reagents of unique function
Coenzyme forms of vitamin B12
Methyl group transfer reactions

The formation and utilization of methyl groups is a quantitatively major aspect of METABOLISM in all Cells. As shown above (Section L.3), methyl groups can be generated by the reduction of one-carbon units attached to tetrahydrofolate. The methyl groups of methyltetrahydrofolate (N⁵—СН₃^-— H₄Fol) can subsequently be transferred to the sulfur atom of homocysteine to yield Methionine:

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Methionine is then converted into S-adenosylmethionine (SAM), virtually the universal methyl group donor in Transmethylation reactions [Reaction (7-1)]. In some Bacteria, Fungi, and higher plants, methyl-H₄Fol:homocysteine transmethylase does not require vitamin B₁₂. However, The Human Body, as well as various strains of E. coli and certain other bacteria, requires a methylcobalamin-dependent enzyme. This enzyme presumably Functions in a cyclic process. It is hypothesized that cobalt alternates between two interconvertible oxidation states (1+ and 3+) [Equation (8-86)].

The first indication of this came from studies by Weissbach, who demonstrated that ¹⁴C-labeled methylcobalamin can be isolated by treating the enzyme with methyl Donors such as S-adenosylmethionine and methyl iodide following reduction (e.g., with reduced riboflavin phosphate). This Treatment corresponds to the laboratory synthesis scheme for methylcobalamin [Reaction (8-73)]. Nevertheless, the MECHANISM OF ACTION of transmethylase is highly complex. The enzyme must first be "activated" by S-adenosylmethionine or methyl iodide, after which it undergoes cycles according to scheme (8-86), but gradually becomes inactivated. The existence of yet another form of the enzyme has been proposed, which is activated through methylation by S-adenosylmethionine [186].