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Cobalt methylcobalamine

The total syntheses have yielded cobyric acid and thence cyanocobalamin. Routes to other cobalamins, eg, methylcobalamin and adenosylcobalamin, are known (76—79). One approach to such compounds involves the oxidative addition of the appropriate alkyl haUde (eg, CH I to give methylcobalamin) or tosylate (eg, 5 -A-tosyladenosine to yield adenosylcobalamine) to cobalt(I)alamine. [Pg.117]

Lenhert and Hodgkin (15) revealed with X-ray diffraction techniques that 5 -deoxyadenosylcobalamin (Bi2-coenzyme) contained a cobalt-carbon o-bond (Fig. 3). The discovery of this stable Co—C-tr-bond interested coordination chemists, and the search for methods of synthesizing coen-zyme-Bi2 together with analogous alkyl-cobalt corrinoids from Vitamin B12 was started. In short order the partial chemical synthesis of 5 -de-oxyadenosylcobalamin was worked out in Smith s laboratory (22), and the chemical synthesis of methylcobalamin provided a second B 12-coenzyme which was found to be active in methyl-transfer enzymes (23). A general reaction for the synthesis of alkylcorrinoids is shown in Fig. 4. [Pg.54]

Fig. 24. 220 MH, NMR spectra of (a) nitroxylmethylcobinamide, (b) methylcobinamide and (c) methylcobalamin at pH 1.2 (base off). In each case the high field peak is the cobalt bound methyl group. In the nitroxyl derivative (a) the methyl group is significantly broadened and shifted downfiek ... Fig. 24. 220 MH, NMR spectra of (a) nitroxylmethylcobinamide, (b) methylcobinamide and (c) methylcobalamin at pH 1.2 (base off). In each case the high field peak is the cobalt bound methyl group. In the nitroxyl derivative (a) the methyl group is significantly broadened and shifted downfiek ...
Figure 15.3 Structural formula of deoxyadenosylcobalamin (coenzyme B, ). (a) A plan view of the corrin nucleus with substituents, (b) The position of the remaining two ligands of the cobalt atom. No attempt is made to show correct stereochemical relationships. Related compounds have different groups in place of the 5 -deoxyadenosyl group cyanocobalamin, (vitamin Bi2)-CN hydroxycobalamin, (vitamin Bi2)-0H methylcobalamin, (vitamin Bi2)-CH3. Figure 15.3 Structural formula of deoxyadenosylcobalamin (coenzyme B, ). (a) A plan view of the corrin nucleus with substituents, (b) The position of the remaining two ligands of the cobalt atom. No attempt is made to show correct stereochemical relationships. Related compounds have different groups in place of the 5 -deoxyadenosyl group cyanocobalamin, (vitamin Bi2)-CN hydroxycobalamin, (vitamin Bi2)-0H methylcobalamin, (vitamin Bi2)-CH3.
The name vitamin B12 indicates a group of cobalt-containing corrinoids, also described as cobala-mins. Hydroxycobalamin (HOCbl), adenosylcobalamin (AdoCbl), and methylcobalamin (MeCbl) are the natural occurring forms. Instead, cyanocobalamin (Figure 19.20) is the commercially available form used for supplements and food fortification, thanks to its greater relative stability. Occasionally, sulfitocobalmin can occur in processed foods. Vitamin B,2 functions as a coenzyme and it is linked to human growth, cell development, and is involved in metabolism of certain amino acids. Vitamin B12 is present mainly in meat and diary foods, therefore a deficiency can occur in... [Pg.633]

Vitamin B12 consists of a porphyrin-like ring with a central cobalt atom attached to a nucleotide. Various organic groups may be covalently bound to the cobalt atom, forming different cobalamins. Deoxyadenosylcobalamin and methylcobalamin are the active forms of the vitamin in humans. Cyanocobalamin and hydroxocobalamin (both available for therapeutic use) and other cobalamins found in food sources are converted to the active forms. The ultimate source of vitamin Bi2 is from microbial synthesis the vitamin is not synthesized by animals or plants. The chief dietary source of vitamin Bi2 is microbially derived vitamin B12 in meat (especially liver), eggs, and dairy products. Vitamin Bi2 is sometimes called extrinsic factor to differentiate it from intrinsic factor, a protein normally secreted by the stomach that is required for gastrointestinal uptake of dietary vitamin B12. [Pg.735]

Vitamin B12 consists of a porphyrin-like ring structure, with an atom of Co chelated at its centre, linked to a nucleotide base, ribose and phosphoric acid (6.34). A number of different groups can be attached to the free ligand site on the cobalt. Cyanocobalamin has -CN at this position and is the commercial and therapeutic form of the vitamin, although the principal dietary forms of B12 are 5 -deoxyadenosylcobalamin (with 5 -deoxyadeno-sine at the R position), methylcobalamin (-CH3) and hydroxocobalamin (-OH). Vitamin B12 acts as a co-factor for methionine synthetase and methylmalonyl CoA mutase. The former enzyme catalyses the transfer of the methyl group of 5-methyl-H4 folate to cobalamin and thence to homocysteine, forming methionine. Methylmalonyl CoA mutase catalyses the conversion of methylmalonyl CoA to succinyl CoA in the mitochondrion. [Pg.206]

The structure of the E. coli enzyme (Fig. 16-24) shows methylcobalamin bound in a base-off conformation, with histidine 759 of the protein replacing dimethylbenzimidazole in the distal coordination position on the cobalt. This histidine is part of a sequence Asp-X-His-X-X-Gly that is found not only in methionine synthase but also in methylmalonyl-CoA mutase, glutamate mutase, and 2-methyleneglutarate mutase. However, diol dehydratase lacks this sequence and binds adenosylcobalamin with the dimethylbenz-imidazole-cobalt bond intact.417... [Pg.875]

The coenzyme evidently functions in a cyclic process. The cobalt alternates between the +1 and +3 oxidation states as shown in Eq. 16-43. The first indication of such a cyclic process was the report by Weissbach that 14C-labeled methylcobalamin could be isolated following treatment of the enzyme with such methyl donors as AdoMet and methyl iodide... [Pg.875]

Although three early papers briefly discussed reactions between methylcobalamin and mercury compounds (30-32), the most systematic investigation has come from Wood and co-workers (33). They proposed the mechanism shown in Fig. 1, with values for the various rate constants presented in Table I. Species 2 and 3, in which the benzimidazole nitrogen no longer bonds to the cobalt atom, are termed base-off compounds, whereas 1 is base-on methylcobalamin and 4 is aquocob(III)alamin, the usual product of aqueous transmethylation by 1. Each one of these species has a unique ultraviolet-visible spectrum, which allows quantitative studies by spectrophotometric techniques to be made (28, 32, 33). The mercuric acetate-1 exchange is so rapid that it must be studied using stopped-flow kinetic techniques (33). [Pg.316]

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). [Pg.343]

Although numerous enzymatic reactions requiring vitamin B12 have been described, and 10 reactions for adenosylcobalamin alone have been identified, only three pathways in man have so far been recognized, one of which has only recently been identified (PI). Two of these require the vitamin in the adenosyl form and the other in the methyl form. These cobalamin coenzymes are formed by a complex reaction sequence which results in the formation of a covalent carbon-cobalt bond between the cobalt nucleus of the vitamin and the methyl or 5 -deoxy-5 -adenosyl ligand, with resulting coenzyme specificity. Adenosylcobalamin is required in the conversion of methylmalonate to succinate (Fig. 2), while methylcobalamin is required by a B12-dependent methionine synthetase that enables the methyl group to be transferred from 5-methyltetrahydrofolate to homocysteine to form methionine (Fig. 3). [Pg.166]

Methylcobalamin (I, R = —CH3) and the vitamin Bi2 coenzyme (I, R = 5 -deoxyadenosyl) are the only known naturally occurring organometailic compounds. Both are derivatives of vitamin 8t2 (cyanocobalamin, I, R = —CN)and both can be synthesized from Bn but are best prepared from hydroxocobalamin. These and numerous other derivatives of Bn containing a cobalt-carbon bond are known, and provided the cobalt is bonded to a primary carbon atom the complexes are thermally very stable, but always photochemically labile as a result of homolytic cleavage of the cobalt-carbon bond. [Pg.134]

Methylcobalamin is a red crystalline solid that is stable in the solid state under ambient conditions. In solution, methylcobalamin is very light sensitive, undergoing homolytic cleavage of the cobalt carbon bond. In dilute acid, protonation of the axial benzimidazole group causes a dramatic change in color from red to... [Pg.137]

Figure 10.12. Vitamin B12. Four coordination sites on the central cobalt atom are occupied by the nitrogen atoms of the corrin ring, and one by the nitrogen of the dimethyl-benzimidazole nucleotide. The sixth coordination site may be occupied by CN cya-nocobalamin, Mr = 1355.4 OH hydroxocobalatnin, Mr = 1346.4 H2O aquocobalamin, Mr = 1347.4 -CH3 methylcobalamin, Mp = 1344.4 and 5 -deoxyadenosine adenosyl-cobalamin, Mr = 1579.6. Figure 10.12. Vitamin B12. Four coordination sites on the central cobalt atom are occupied by the nitrogen atoms of the corrin ring, and one by the nitrogen of the dimethyl-benzimidazole nucleotide. The sixth coordination site may be occupied by CN cya-nocobalamin, Mr = 1355.4 OH hydroxocobalatnin, Mr = 1346.4 H2O aquocobalamin, Mr = 1347.4 -CH3 methylcobalamin, Mp = 1344.4 and 5 -deoxyadenosine adenosyl-cobalamin, Mr = 1579.6.
The cobalt-bound methyl group of (4) is not readily removed by acid. Treatment of (4) with acid in aqueous solution leads to proteolytic decoordination of the nucleotide base (pXa = 2.9). The cobalt-bound methyl group of methyl-Co "-corrins can be abstracted (1) by nucleophiles, such as thiol(ate)s, " > " (2) by radicaloid species, such as other Co"-corrins, or (3) by electrophilic species, such as Hg"-ions. A reversible and rapid methyl-group transfer occurs in deoxygenated aqueous solution between methyl-Co "-corrins and Co -corrins. From the pair, methyl-Co "-cobinamide and Co -cobalamin (6), methylcobalamin (4) and Co -cobinamide are generated and prevail at equilibrium. [Pg.805]

In view of the coordination pattern in protein-bound methylcobalamin (see below), the thermodynamic studies on the effect of the coordination of the dimethylbenzimidazole base to the a-side of the cobalt center on the homolytic and heterolytic (Co/3-C)-bond dissociation energy in (4) (thermodynamic effect of the trans hgand or trans influence ) were extended to corresponding investigations with CojS-methyl-imidazolylcobamides, such as (9), where imidazole replaces the dimethylbenzimidazole these studies showed this change of the nature of the axial base to have httle effect on the two relevant bond-dissociation energies of the corresponding methylcobamide. ... [Pg.805]

The various photochemical studies of these compounds have been conducted primarily because of the interest of researchers in the synthesis, properties, and biological activity of vitamin and its derivatives. The structure of vitamin Bj2, as determined by Crowfoot-Hodgkin et al. 109), is shown in Fig. 2. It consists of cobalt in a corrin ring complexed axially by an a-S, 6-dimethylbenzimidazole nucleotide and by cyanide ion. Replacement of the axial CN by a methyl group gives methylcobalamin, and by 5 -deoxyadenosine gives coenzyme Bj2. The formal oxidation state of... [Pg.302]

Most alkylcobalamin derivatives are thermally stable but are photosensitive. When irradiated in the presence of O2, methylcobalamin gives formation of formaldehyde and a cobalt (III) aquo complex [Eq. (102)]. [Pg.303]

ESR studies 112,114-118a) are also consistent with the formation of free radicals upon photolysis of alkylcobalamin and coenzyme Bi2- For example, Lappert and co-workers 116) demonstrated that homolysis of the cobalt-alkyl bond occurs upon photolysis of coenzyme B12 and ethylcobalamin by trapping the S -deoxyadenosyl and ethyl radicals produced with (CH3)3CN0. They were able to detect the spin-trapped (CH3)3CN(0)R radicals by ESR spectroscopy. Homolysis of the cobalt-methyl bond was also shown to occur upon anaerobic photolysis of methylcobalamin 117). However, the presence of traces of oxygen in the methanol solvent was shown to affect signiflcantly the photochemistry of methylcobalamin 118). Indeed, under those conditions, the 5,S-dimethyl-1-pyrroline iV-oxide (DMPO) spin adducts of both the methyl and hydrogen radicals, 113 and 114, respectively, were detected by ESR spectro-... [Pg.304]

Figure 1 In the above structure, R = CN denotes cyanocobalamin (CN-Cbl), whilst R = OH is hydroxocobalamin (OH-Cbl) R = 5 -deoxyadenosyl is coenzyme B12 (adenosylcobalamin, AdoCbl) and R = Me is methylcobalamin (MeCbl). By definition all cobalamins contain 5,6-dimethylbenzimidazole, which is the so-called 6th ligand to cobalt in the above structure. Substances containing the corrin ligand, i.e. the planar 14 electron p-system embracing cobalt in the above structure, are also called corrinoids. Figure 1 In the above structure, R = CN denotes cyanocobalamin (CN-Cbl), whilst R = OH is hydroxocobalamin (OH-Cbl) R = 5 -deoxyadenosyl is coenzyme B12 (adenosylcobalamin, AdoCbl) and R = Me is methylcobalamin (MeCbl). By definition all cobalamins contain 5,6-dimethylbenzimidazole, which is the so-called 6th ligand to cobalt in the above structure. Substances containing the corrin ligand, i.e. the planar 14 electron p-system embracing cobalt in the above structure, are also called corrinoids.

See other pages where Cobalt methylcobalamine is mentioned: [Pg.104]    [Pg.111]    [Pg.113]    [Pg.113]    [Pg.597]    [Pg.338]    [Pg.341]    [Pg.57]    [Pg.62]    [Pg.67]    [Pg.264]    [Pg.140]    [Pg.7]    [Pg.46]    [Pg.373]    [Pg.391]    [Pg.315]    [Pg.637]    [Pg.165]    [Pg.181]    [Pg.135]    [Pg.301]    [Pg.352]    [Pg.805]    [Pg.807]    [Pg.4843]    [Pg.304]    [Pg.305]    [Pg.64]   
See also in sourсe #XX -- [ Pg.18 ]




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