Corrinoids biological methylation

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... 

Vitamin B12 is a biologically active corrinoid, a group of cobalt-containing compounds with macrocyclic pyrrol rings. Vitamin B12 functions as a cofactor for two enzymes, methionine synthase and L-methylmalonyl coenzyme A (CoA) mutase. Methionine synthase requires methylcobalamin for the methyl transfer from methyltetrahydrofolate to homocysteine to form methionine tetrahy-drofolate. L-methylmalonyl-CoA mutase requires adenosylcobalamin to convert L-methylmalonyl-CoA to succinyl-CoA in an isomerization reaction. An inadequate supply of vitamin B12 results in neuropathy, megaloblastic anemia, and gastrointestinal symptoms (Baik and Russell, 1999). 

The metabolically important functions of the Bn-derivatives are directly concerned either with enzymatically controlled organometalhc reactions involving protein-bound adenosylcobamides (such as coenzyme B12, (3)), or methyl-Co -corrinoids (such as methylcobalamin, (4)), or with enzyme-controlled redox reactions. Studies on the underlying biologically relevant organometalhc chemistry of the Bi2-coenzymes in homogeneous (protic) solution, as well as the characterization of the enzymatic processes themselves have attracted considerable interest. ... 

In biological systems the two-electron reduction may be accomplished by NADH and flavin adenine dinucleotide (FAD). The methyl donor is N -methylletrahydrofo(ate (CH -THF). The Co(Ill) corrinoid (methylcobalamin) can then partake in biomethyla-tion reactions ... 

Progress of biological action in enzymatic methyl transfer and rearrangement reactions, medicinal aspects, structure and reactivity, and biosynthesis of vitamin B12 and B 12-coenzymes was very recently comprehensively presented at the 4 European Symposium on Vitamin Bi2 and B 12-Proteins and reviewed in an excellent monograph (70). Therefore it is intended with this contribution to address mainly results from research in the field of vitamin B12 biosynthesis. The procedure makes sense because of two reasons. First, many of the biosynthetic intermediates are closely related to hydroporphyrinoid structures discussed in previous sections and second, reactions of the biosynthetic pathway concern the chemistry of the hydroporphyrinoid and corrinoid frameworks involved, whereas the biochemical reactivity of vitamin B12 is mainly restricted to the central cobalt ion of the corrin macrocycle. 

The bacterial metalloenzyme acetyl coenzyme A synthase/CO dehydrogenase (ACS/CODH) catalyzes two very important biological processes, namely the reduction of atmospheric CO2 to CO and the synthesis of acetyl coerrzyme A from CO, a methyl from a methylated corrinoid iron-sulfur protein, and the thiol coenzyme A [166-168]. This bifunctional errzyme is the key to the Wood-Ljiungahl pathway of anaerobic CO2 fixation (Scheme 1.18) and a major component of the global carbon cycle. Reactions catalyzed by CODH and ACS are shown in Eqs. (1.4) and (1.5) below. 

The clarification of the structure of coenzyme B g stimulated attempts to synthesize the compound from vitamin B g and an activated adenosine derivative. Smith et described a chemical synthesis of the coentyme from fully reduced vitamin Big (Bi and the 5 -tosyl-2, 3 -isopropylidene derivative of adenosine. At the same time they reported the synthesis of Co-methyl-cobalamin from Bigg and methyl iodide. Soon thereafter a biological function of methylcobalamin in the methylation of homo steine was demonstrated by Guest et Only one other Co-alkyl-corrinoid compound has so far been... 

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