Cobalamin vitamin 5 -deoxyadenosyl

Vitamin B12 Cobalamin Methylcobalamin Deoxyadenosyl cobalamin Cofactor for reactions Homocysteine > Methionine I Methylmalonyl CoA -> Succinyl CoA j... 

Deoxyadenosyl cobalamin Cobalamin (vitamin B12) Pernicious anemia... 

It soon became apparent that the biologically active forms of Vitamin Bj.2 contained the unique Co—C-a-bond, and the instability of these covalent compounds to visible light facilitated observations on the occurrence of functional corrinoids in a number of enzymes. Deoxyadenosyl-cobalamin was found to be the most abundant corrinoid in bacteria (24) and in mammalian liver (25). Methylcobalamin was found in Escherichia coli (26), calf liver and human blood plasma (27), and also in a number of Clostridia (28). 

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). 

Vitamin B12 (cobalamin) has as its active forms, methylcobalamin and deoxyadenosyl cobalamin. It serves as a cofactor for the conversion of homocysteine to methionine, and methylmalonyl CoA to succinyl CoA. A deficiency of cobalamin results in pernicious (megaloblastic) anemia, dementia, and spinal degeneration. The anemia is treated with IM or high oral doses of vitamin B12. There is no known toxicity for this vitamin. 

Vitamin B12 Precursor of the coenzyme deoxyadenosyl cobalamin. Deficiency leads to pernicious... 

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... 

Scheme 2 Structure of cobalamin, where X = CN for cyanocobalamin (vitamin Bi2), X = H20 for aquacobalamin (vitamin Bi2a) and X = 5 -deoxyadenosyl for coenzyme B12.

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. 

Since the coenzyme from vitamin is required in two distinct enzyme reactions, i.e., remethylation of homocystine and catabolism of methylmalonic acid, the fundamental defect must involve a step in converting to its coenzymes. Formation of both deoxyadenosyl B and methyl B requires a prior reductive step catalyzed by cobalamin reductase, which appears to be the defective enzyme in this variant (Hogervorst et al., 2002) (Fig. 20.4). 

Methylmalonyl-CoA mutase (EC 5.4.99.2). Failure to convert (/ )-methylmalonyl-CoA into succinyl-CoA. Large quantities of methylmalonic acid appear in plasma and urine. Affected children fail to thrive and show pronounced ketoacidosis. Often fatal in early life. Hyperammonemia and intermittent hyperglycinemia are also typical. Restricted protein intake and synthetic diets are helpful, in particular low intakes of leucine, isoleucine, valine, threonine and methionine. A similar condition may arise from a congenital deficiency of methylmalonyl-CoA epimerase (EC 5.1.99.1). Both conditions unresponsive to vitamin Bj2. Another type of methylmalonyl aciduria is thought to result from an hereditary deficiency of deoxyadenosyl transferase (transfers the 5 -deoxyade-nosyl group in cobalamin synthesis), which provides the coenzyme of methylmalonyl-CoA mutase. This condition responds to injection of B,2. Dietary B12 deficiency also results in methylmalonic aciduria. 

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)... 

Cyanocobalamin (Formula 6.17) was isolated in 1948 from Lactobacillus lactis. Due to its stability and availability, it is the form in which the vitamin is used most often. In fact, cyanocobalamin is formed as an artifact in the processing of biological materials. Cobalamins occur naturally as adenosylcobalamin and methylcobalamin, which instead of the cyano group contain a 5 -deoxyadenosyl residue and a methyl group respectively. 

With the refined chromatographic techniques now available for the identification of plasma cobalamins, it has been shown that two-thirds of normal subjects do not have any cyanocobalamin in plasma, and the remainder have only traces, most of the vitamin B12 being in the forms of hydroxocobdamin, methylcobalamin and 5 -deoxyadenosyl i2 ( co-enzyme B12 ). The low cyanocobalamin levels may reflect equilibrating mechanisms which prevent the toted conversion of vitamin B12 to cyanocobalamin which would be expected from the exposure to large eimounts of cyanide by tobacco smokers [56]. 

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