Catalysis of Methyl Group Transfers Involving Tetrahydrofolate and B12

Abstract

This review focuses on the reaction mechanism of enzymes that use B(12) and tetrahydrofolate (THF) to catalyze methyl group transfers. It also covers the related reactions that use B(12) and tetrahydromethanopterin (THMPT), which is a THF analog used by archaea. In the past decade, our understanding of the mechanisms of these enzymes has increased greatly because the crystal structures for three classes of B(12)-dependent methyltransferases have become available and because biophysical and kinetic studies have elucidated the intermediates involved in catalysis. These steps include binding of the cofactors and substrates, activation of the methyl donors and acceptors, the methyl transfer reaction itself, and product dissociation. Activation of the methyl donor in one class of methyltransferases is achieved by an unexpected proton transfer mechanism. The cobalt (Co) ion within the B(12) macrocycle must be in the Co(I) oxidation state to serve as a nucleophile in the methyl transfer reaction. Recent studies have uncovered important principles that control how this highly reducing active state of B(12) is generated and maintained.

Acetogenesis and the Wood–Ljungdahl pathway of CO2 fixation

“…This reaction is similar to the first step in the reaction mechanism of cobalamin-dependent methionine synthase [80, 167]. As noted in Equation 19, cobalt undergoes redox changes during the reaction and, as in other cobalamin-dependent methyltransferases [168], Co(I) is the only state that can catalyze methyl transfer, forming an alkyl-Co(III) product. The redox chemistry involving the CFeSP will be covered in the next section.…”

“…While MeTr catalyzes methyl transfer from methyl-H 4 folate, various cobalamin-dependent methyltransferases are found in biology, which react with a wide range of natural methyl donors, including methanol, methylamines, methyl thiols, and aromatic methyl ethers [168]. Structural and kinetic studies have been performed to attempt to understand how the methyltransferases catalyze the methyl transfer reaction.…”

Site-Directed Mutagenesis of HgcA and HgcB Reveals Amino Acid Residues Important for Mercury Methylation

“…The HgcA C-terminal domain contains four or five predicted transmembrane helices with no homology to CFeSP or any other protein. For the catalytic function of CFeSP, the cob(I)amide cofactor receives a methyl group as a carbocation from methyltetrahydrofolate via the methyltetrahydrofolate:CFeSP methyltransferase (MeTr) to produce methylcob(III)amide (25,26). This route has been suggested for HgcA (12); however, subsequent methyl group transfer as a carbanion to Hg(II) would result in a Co(III) intermediate (25,27).…”

Padidėjęs Jautrumas Maisto Priedams: Glutamato Klinikiniai Aspektai

“…Ji yra tripeptido glutationo, kuriame dar yra aminorūgštys cisteinas ir glicinas, sudėtyje. Glu apsaugo ląsteles nuo žalingų aktyvių deguonies junginių poveikio [15,16] ir yra svarbus DNR ir aminorūgščių apykaitos reakcijose [17,18]. Jis ir dekarboksilinimo reakcijos metu susidaręs γ-aminobutiratas -GABA ("gama aminobutyric acid") yra nervinio impulso perdavimo tarpininkai -neurosiuntikliai [19,20,21,22,23].…”