Enzymes containing cobalt corrinoids

The reactions which are catalyzed by enzymes containing cobalt corrinoids can be classified into three groups. 

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. 

Most living organisms depend on catalysis by the transition element cobalt (1). The biological relevance of cobalt is due, mainly, to vitamin B12 derivatives (2,3), also known as cobalt corrinoids (4). In exceptional cases, enzymes may contain natural noncorrinoid cobalt ions (5), and structural Zn centers have been reconstituted with Co (and other divalent metal) ions, without significant loss of activity (1,4). Only some microorganisms are able to produce B12 derivatives naturally (6,7). Cobalt complexes similar to vitamin B12 (1) may have had fundamental roles in early forms of life on earth (1,8). 

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). 

Studies on protein-free corrinoids and model complexes have shown that increasing the steric bulkiness around the coordinated Ca atom can cause a dramatic labilization of the Co—C bond. The protein-coenzyme adduct might contain the coenzyme in a resting state and the protein in a strained state the substrate would then switch the system into a strained coenzyme and a relaxed enzyme with little thermodynamic barrier. The strained form of the coenzyme is then in labile equilibrium with base-on cobalt(II) and the free radical. " This hypothesis, that conformational changes in cobalamin can switch chemical reactions on and off, is closely analogous with the known aspects of hemoglobin function. 

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