Deoxyadenosyl cobalamin

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

Ribonucleotide reductase differs from the other 5 -deoxyadenosyl-cobalamin requiring enzymes in a number of respects. Hydrogen is transferred from coenzyme to the C2-position of the ribose moiety without inversion of configuration. Also since lipoic acid functions in hydrogen transfer, exchange with solvent protons takes place. Furthermore, exchange between free and bound 5 -deoxyadenosylcobalamin occurs rapidly during catalysis. Evidence for a Co(I)-corrin as an intermediate for this reduction is presented in our section on electron spin resonance. 

Various coenzymes are involved in these reactions. The carboxylase [3] requires biotin, and the mutase [4] is dependent on coenzyme Bj2 (5 -deoxyadenosyl cobalamin see p. 108). Succinyl-CoA is an intermediate in the tricar-... 

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. 

Structure of vitamin B12 (cyanocobalamin) and its coenzyme forms (methylcobalamin and 5 -deoxyadenosyl-cobalamin). 

C (ascorbic acid) 5 -Deoxyadenosyl cobalamin Transfer of methyl groups intramolecular rearrangements Antioxidant Anemia, pernicious anemia, methylmalonic acidosis Scurvy (swollen and bleeding gums, subdermal hemorrhages)... 

The main biological and biochemical interest in cobalt concerns vitamin B,2 and a number of its derivatives, such as 5 -deoxyadenosyl cobalamin, which function as coenzyme in a number of rearrangements involving hydrogen shifts and aquocobalamin which is involved in the synthesis of methionine, methane and acetate. Vitamin in its resting state is ESR-inactive since it contains Co , but, when reduced to Co, spectra such as that shown in Figure 4.7 are obtained. This reduced form is referred to as vitamin B,2r it does not have cyanide as a sixth ligand. Its... 

The 5-deoxyadenosyl cobalamin and methyl cobalamin function as coenzyme forms and are required for the action of several enzymes. Methyl malonyl CoA mutase uses 5-deoxyadenosyl cobalamin as coenzyme. Methyl cobalamin functions as a carrier of methyl group to homocysteine and convert it to methionine... 

Figure 30 IS The structure of 5 -deoxyadenosyl cobalamin. (Modified from Chanarin l The megaloblastic anemias, 2nd edition, Oxford Blackwell Scientific, 1979.)...

Bi2 (Cobalamin) 5-deoxyadenosyl cobalamin Intramolecular rearrangements Prosthetic group... 

Certain biological processes, notably coenzyme B, -dependent rearrangements, also are triggered by enzyme-induced homolytic Co-C bond dissociation of the coenzyme, Equation 4 (coenzyme B-j 5 -deoxyadenosyl cobalamin, abbreviated Ado-B min). 

Description. Vitamin B12 is the largest and most complex of all the vitamins. It is unique among vitamins in that it contains a metal ion, cobalt. For this reason cobalamin is the term used to refer to compounds having B12 activity. Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of vitamin B12 used in the human body. The form of cobalamin used in most supplements, cyano-cobalamin, is readily converted to 5-deoxyadenosyl and methylcobalamin. 

Fig. 2. Mechanism of action of 5-deoxyadenosyl-cobalamin as the cofactor of propanediol dehydratase (EC 4.2.1.28). The mechanism is supported by the migration of from Cl of the substrate to C2 of the substrate and C5 of the cofactor. The same enzyme aiso dehydrates ethylene giycoi to acetaidehyde.

Cobalamins Aquocobalamin, methylcobalamin and 5 -deoxyadenosyl-cobalamin (D 10.3) Coenzymes of tetrahydrofolate-dependent methyltransferases and of isomerates (D 10.3), vitamins for humans (vitamin Bj2)... 

Type II Methylmalonic acid, homocystine, cystathionine Failure of cellular cobalamin accumulation and/or retention with secondary failure of both methyl-cobsdamin and 5 -deoxyadenosyl-cobalamin synthesis 11.1... 

Mahoney, M.J., Hart, A.C., Steen, V.D. and Rosenberg, L.E. (1975a), Methyl-malonicacidemia Biochemical heterogeneity in defects of 5 -deoxyadenosyl-cobalamin synthesis. Proc. Natl. Acad. Sci. U.S.A., 72,2799. 

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