B12 coenzyme

Naturally occurring compounds with carbon-metal bonds are very rare The best example of such an organometallic compound is coenzyme Bi2 which has a carbon-cobalt ct bond (Figure 14 4) Pernicious anemia results from a coenzyme B12 deficiency and can be treated by adding sources of cobalt to the diet One source of cobalt IS vitamin B12 a compound structurally related to but not identical with coen zyme B12... 

Towards the unification of coenzyme B12-dependent diol dehydratase stereochemical and model studies the bound radical mechanism. R. G. Finke, D. A. Schiraldi and B. J. Mayer, Coord. Chem. Rev., 1984, 54,1-22 (40). 

New developments in the field of vitamin B12 enzymatic reactions dependent upon corrins and coenzyme B12. G. N. Schrauzer, Angew. Chem., Int. Ed. Engl., 1977,16, 233-244 (89). 

Naturally, the biosynthesis of cobalamins themselves require delivery of Co ions at a particular point in the reaction scheme. Cobaltochelatase catalyzes the ATP-dependent insertion of Co11 into the corrin ring during the biosynthesis of coenzyme B12 in Pseudomonas denitrifleans. Cobaltochelatase is a heterodimeric enzyme (140 KDA and 450 KDA subunits each inactive in isolation), and the two components have been isolated and purified to homogeneity.1119 The reaction product is divalent cobyrinic acid, demonstrating that hydrogenobyrinic acid and its diamide (255) are precursors of AdoCbl. 

There are two other interesting features of the PMR spectra of B12 derivatives which should be mentioned. In the spectrum of coenzyme-B12 where the cobalt bound alkyl group is 5 -deoxyadenosyl, two high field peaks, each with the intensity of one proton, are observed (130). These correspond to the two 5 -methylenic protons. 

Methyl-Cobalamine and Related Compounds. There are three major types of cobalamine in animals and man, the methyl and hydroxo derivatives and the deoxyadenosyl derivative (coenzyme B12). The unique metal-carbon bond in the methyl derivative and in B12 is extremely photolabile, and their photolyses have been widely studied. However, radiolytic processes have not been widely studied. 

Haem, Fe Chlorophyll, Mg Coenzyme B12, Co Factor F-430, Ni Electron transfer in membranes and elsewhere Light capture and transduction in membranes Transfer of methyl, rearrangements of substrates Activation of carbon monoxide... 

Chandra and Brown66 investigated the synthesis of x-ribonucleosides as mimetics of the lower axial ligand in coenzyme B12. Reaction of unprotected indolines with... 

The substitution behavior of coenzyme B12, in which a cobalt-carbon bond is present between the Co(III) center and the 5 -desoxy-... 

Like many vitamins, cobalamin is functionally active as a derived coenzyme, coenzyme B12. Structurally, this is composed of a corrin ring a haem-like porphyrin ring containing cobalt (Co3+) at the centre held by four coordination bonds. The fifth... 

Vitamin Bj2 is converted to co-enzyme B12 by extracts from microorganisms supplemented with ATP Coenzyme B12 is associated with many biochemical reactions-... 

In addition to the isomerization of glutamic acid, several other coenzyme B12-catalyzed reactions have now been discovered (I, 9, 15, 31, 51). The conversion of methylmalonic acid to succinic acid is very similar, and has been shown to occur through the migration of a carboxyl group, and postulated to involve free radical itermediates, as follows (15) ... 

If this scheme is correct, two of the steps in this reaction would require a catalyst the removal of a hydrogen atom in step 1 and the addition of a hydrogen atom in step 3. The vital question then becomes how the coenzyme B12 can participate in this exchange of hydrogens. 

Propionyl-CoA is first carboxylated to form the d stereoisomer of methylmalonyl-CoA (Pig. 17—11) by propionyl-CoA carboxylase, which contains the cofactor biotin. In this enzymatic reaction, as in the pyruvate carboxylase reaction (see Pig. 16-16), C02 (or its hydrated ion, HCO ) is activated by attachment to biotin before its transfer to the substrate, in this case the propionate moiety. Formation of the carboxybiotin intermediate requires energy, which is provided by the cleavage of ATP to ADP and Pi- The D-methylmalonyl-CoA thus formed is enzymatically epimerized to its l stereoisomer by methylmalonyl-CoA epimerase (Pig. 17-11). The L-methylmal onyl -CoA then undergoes an intramolecular rearrangement to form succinyl-CoA, which can enter the citric acid cycle. This rearrangement is catalyzed by methylmalonyl-CoA mutase, which requires as its coenzyme 5 -deoxyadenosyl-cobalamin, or coenzyme Bi2, which is derived from vitamin B12 (cobalamin). Box 17—2 describes the role of coenzyme B12 in this remarkable exchange reaction. 

Coenzyme B12 is the cofactor form of vitamin B 2, which is unique among all the vitamins in that it contains not only a complex organic molecule but an essential trace element, cobalt. The complex corrin ring system of vitamin B12 (colored blue in Fig. 2), to which cobalt (as Co3+) is coordinated, is chemically related to the porphyrin ring system of heme and heme proteins (see Fig. 5-1). A fifth coordination position of cobalt is filled by dimethylbenzimidazole ribonucleotide (shaded yellow), bound covalently by its 3 -phosphate group to a side chain of the corrin ring, through aminoisopropanol. 

The key to understanding how coenzyme B12 catalyzes hydrogen exchange lies in the properties of the covalent bond between cobalt and C-5 of the deoxyadeno-... 

Oxidation of unsaturated fatty acids requires two additional enzymes enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase. Odd-number fatty acids are oxidized by the /3-oxidation pathway to yield acetyl-CoA and a molecule of propionyl-CoA This is carboxylated to methylmalonyl-CoA, which is isomerized to succinyl-CoA in a reaction catalyzed by methylmalonyl-CoA mutase, an enzyme requiring coenzyme B12. 

A review of the biochemistry of coenzyme B12 reactions, including the methylmalonyl-CoA mutase reaction. 

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