Methylcob

FIGURE 10.3 Structural formula of vitamin B[2 and partial structures of vitamin B[2 compounds. The partial structures of vitamin B,2 compounds show only those portions of the molecule that differ from vitamin B[2. 1 — 5 -deoxyadenosylcobalamin, 2 — methylcobal-amin, 3 — hydroxocobalamin, 4 — cyanocobalamin, 5 — benzimidazolyl cyanocobamide, 6 — pseudovitamin B[2, 7 — 5-hydroxybenzimidazolyl cyanocobamide, 8 — p-cresolyl cyanocobamide. 

The presence of Au(I) may likewise catalyze the reaction of Au(III) with methylcob(III)alamin Wood has included this couple under his Redox Switch category. Like PtCl l-, the reaction of AuC14 with CH3B12 is enhanced by the presence of Br" (46). It remains to be proven that the Au reaction does involve methyl radical transfer, presumably with subsequent oxidation of B12r [a cob(II)alamin compound] to the observed aquocobalamin. However, the available evidence for the formation of Au(II) intermediates is more extensive and convincing (200) than for Pt(III) intermediates (201). 

The Bj2 vitamers consist of a group of organometallic compounds that have a common cor-rinoid structure and vary in the substituent bound to the central cobalt atom (Fig. 7) (167,168). The principal naturally occurring Bl2 vitamers are hydroxocobalamin (HOCbl), methylcobal-amin (MeCbl), and adenosylcobalamin (AdoCbl). Cyanocobalamin (CNCbl) is the form commonly used for clinical, pharmaceutical, and food fortification purposes, due to its greater relative stability. 

The one exception is the capacity of some micro-organisms to methylate certain metals, e.g. arsenic, antimony and mercury, probably as a kind of detoxification mechanism. Methylcobal-amin is the only organometallic compound known to have a physiological function in life processes. 

Microorganisms can transfer methyl groups to various heavy metals and metalloids (e.g., Se, As), which results in mobilizing these heavy metals and promoting their potentiation as environmental toxicants. Such methylation is attributed to the enzymatic system involved in the anaerobic generation of methane, where the methyl donor is methylcobal-amin (methyl vitamin B12). This is exemplified by the case of mercury (see Figure 9.12). 

In mammals, there are only three vitamin B12 -dependent enzymes methionine synthetase, methylmalonyl CoA mutase, and leucine aminomutase. The enzymes use different coenzymes methionine synthetase uses methylcobal-amin, and cobalt undergoes oxidation during the reaction methylmalonyl CoA mutase and leucine aminomutase use adenosylcobalamin and catalyze the formation of a 5 -deoxyadenosyl radical as the catalytic intermediate. 

The synthesis of acetyl-CoA by the Ljungdahl-Wood pathway of autotrophic carbon fixation in diverse bacteria and archaea is catalyzed by a Co- and Fe-containing corrinoid iron-sulfur protein (CoFeSP). This protein participates in the transfer of a methyl group from A -methyltetrahydrofolate to the cob(I)amide of CoFeSP to give a methylcob(III)amide, from which the methyl group is transferred to the reduced Ni-Ni-(4Fe-4S) active site cluster A of acetyl-CoA synthase (27). 

The coenzyme that mediates this transfer of a methyl group is methylcobal-min, derived from vitamin In fact, this reaction and the rearrangement of L-methylmalonyl CoA to succinyl CoA (p. 628), catalyzed by a... 

Cobalamin-catalyzed reactions are generally classified into two groups methylcob-alamin-dependent reactions (Table 1, entry 1 to 3) and coenzyme Bi2-dependent rearrangements (Table 1, entry 4 to 11). The first group includes the biosynthesis of methionine from homocysteine, the reduction of CO2 to acetic acid via an acetyl-CoA pathway, and the biosynthesis of CH4 also via an acetyl-CoA pathway. ... 

Figure 3 Absorption spectra of cobalamins in three oxidation states. The spectra are of (—) methylcob(lll)alamin, (-)...

Cleavage of methylvitamin Bn Cupric chloride in conjunction with lith-liini chloride cleaves the Co—CH3 bond of methylvitamin Bu (methylcobal-tiinln) to give aquovitamin B12. A complex of the type Cu (HjO)3(Cr)2 is... 

Methylcorrinoids are competent for the efficient methylation of alkyl radicals. Thermolysis of 2 -bis(ethoxycarbonyl)propylcobalamin and methylcobalamin at 70 °C led to formation of cob(II)alamin and the organic products 2-ethyl-2-methylmalonic acid diethyl ester and 2,2-dimethylmalonic acid diethyl ester. The former product was generated with quantitative deuterium incorporation from CDsCobjllljalamin. The proposed mechanism involves homolytic substitution on methylcob(III)alamin by the 2 -bis(ethoxycarbonyl)propyl radical, resulting in net methyl-radical abstraction, a process calculated to be highly exothermic (A7/ -201 kJmoK ). The stereochemical course of the reaction should result in net inversion at the methyl carbon, although this has not been demonstrated. The reaction may serve as a precedent for several biosynthetic methylations, such as the antibiotic thienamycin synthesis. ... 

In aqueous solution and at room temperature the base-on (hexacoordinate) methylcob(III)alamin is more stable by about 4 kcal/mol than the base-off COo -aquo-COje-methylcob(III)alamin [135]. From NMR studies, the latter has been estimated to still be more stable in water, by around 7 kcal/mol, than the corresponding base-off and dehydrated form of Co -methylcob(III)alamin, which has a pentacoordinate Co -methyl-Co(III)-center [136]. 

Figure 2, Catalysis and reactivation of methionine synthase. Methionine for,motion occurs via two half reactions in which cobalamin serves as the intermediate methyl carrier. Reactivation is depicted in the right-hand portion of the diagram. An electron donor and AdoMet convert the inactive cob(II)alamin form of the enzyme to methylcob(III)alamin. In E. colU flavodoxin serves as the reductant for this priming reaction (7).

In contrast, the activation conformation appears to be unpopulated in methylated MetH. The methylcob(III)alamin enzyme retains the spectral signature of base-on cobalamin in the presence of flavodoxin and flavodoxin is not bound (K is > 70 pM) 4 ). These observations imply that AG for dissociation of histidine from cobalt is much more positive in methylcobalamin MetH than in the cob(II)alamin form of the enzyme. 

The unexpectedly high concentrations of mercury found in water and in fish tissues result from the formation of soluble monomethylmercury ion, CHjHg, and volatile dimethylmercury, (CH3)2Hg, by anaerobic bacteria in sediments. Mercury from these compounds becomes concentrated in fish lipid (fat) tissue and the concentration factor from water to fish may exceed 10. The methylating agent by which inorganic mercury is converted to methylmercury compounds is methylcobal-amin, a vitamin Bj2 analog ... 

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