Cobalamins structure

Figure 12.5 Cobalamine structures. From Lippard and Berg, 1994. Reproduced by permission of University Science Books.

In these compounds the cobalt atom is enclosed in a highly conjugated cobalamin structure and linked to an alkyl group via a metal-carbon bond. The B12 coenzymes are diamagnetic and can be regarded as complexes of cobalt(III) with a carbanion as a ligand (2). As this review will be limited to cases of direct metal-protein interactions the corrinoids will not be discussed further. 

Vitamin B12 must be converted into its coenzyme forms, adenosylcobalamin and methylcobalamin, in the cell. These coenzymes function as cofactors of methylmalonyl-CoA mutase and methionine synthase, respectively. Chronic kidney disease (CKD) may affect the conversion from vitamin B12 to the coenzyme forms. This section describes the intracellular metabolism of cyanocobalamin, which is included in many dietary supplements, in particular, referring to a recently discovered trafficking chaperone called methylmalonic aciduria cdlC type with homocystinuria (MMACHC). Cyanocobalamin is first converted to cob(II)alamin, which has no cyanogen group on the ligand occupying the upper axial position of the cobalamin structure. Cob(II)alamin is further reduced to cob(I)alamin, which can function as a coenzyme in the body. 

In cobalamin, vitamin Bu, one of the six ligands forming an octahedral structure around a cobalt atom is an organic molecule attached through a carbon-cobalt bond (red). The bond is weak and easily broken. 

The mechanistic and structural chemistry of B12 may be separated into (i) investigations of cobalamin cofactors both apart from and in complex with their enzymes, and (ii) biomimetic model complexes, both structural and functional. 

Figure 15.8 (a) Structure and (b) alternative conformations of cobalamine found in B12-dependent enzymes. The functional group R is deoxyadenosine in AdoCbl, methyl in MeCbl and -CN in vitamin B12. (From Bannerjee and Ragsdale, 2003. Reprinted with permission from Annual Reviews.)... 

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... 

The structure of cobalamin is more complex than that of folic acid (Figure 15.2 and 15.3). At its heart is a porphyrin ring containing the metal ion cobalt at its centre. In catalytic reactions the cobalt ion forms a bond with the one-carbon group, which is then transferred from one compound to another. Vitamin B12 is the prosthetic group of only two enzymes, methylmalonyl-CoAmutase and methionine synthase. The latter enzyme is particularly important, as it is essential for the synthesis of nucleotides which indicates the importance of vitamin B12 in maintenance of good health. 

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. 

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

In addition to provision of carbon, other nutrients required by microorganisms embrace nitrogen, phosphorus, and oxygen, all elements of which are part of the structural and functional molecules of the cell. Smaller quantities of micronutricnLs are needed. The requirement for cobalt in the synthesis of cobalamin is one of these obvious requirements. 

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