Corrin ring, coenzyme

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. 

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... 

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. 

Among the chemical forms adopted by the vitamin B12 coenzyme, one is a terminal hydride of the type CoHL5 where L represents a nitrogen ligand of the corrin ring or axial base. Hydrides may be important in vivo both in this case and in that of hydrogenases. 

Several macrocyclic ligands are shown in Figure 2. The porphyrin and corrin ring systems are well known, the latter for the cobalt-containing vitamin Bi2 coenzymes. Of more recent interest are the hydroporphyrins. Siroheme (an isobacteriochlorin) is the prosthetic group of the sulfite and nitrite reductases which catalyze the six-electron reductions of sulfite and nitrite to H2S and NH3 respectively. The demetallated form of siroheme, sirohydrochlorin, is an intermediate in the biosynthesis of vitamin Bi2, and so links the porphyrin and corrin macrocycles. Factor 430 is a tetrahydroporphyrin, and as its nickel complex is the prosthetic group of methyl coenzyme M reductase. F430 shows structural similarities to both siroheme and corrin. 

Fig. 9.4. Vitamin B, coenzyme structure, showing bonding of deoxy-adenosyl carbanion to cobalt(III). Four of the five N atoms bonded to Co are furnished by the corrin ring and one is from a benzimidazole group.

The Co(III)—C bond in the natural coenzymes is resistant to cleavage in protic solvents. However, the bond length [20] is similar to that in models. Indeed, there appear to be no special corrin ring electronic properties necessary for such water-stable Co—C bonds even Co(III)—CH3 compounds with classical ligands such as ammonia or ethylenediamine have now been discovered [21], Although such non-Bi2-related systems are outside the scope of this review, I believe that the main reason that few such compounds are known lies in the paucity of synthetic routes. Since the Co—C bond, once formed, is relatively inert, such compounds could be used for multiple types of applications such as in molecular assemblies or devices [22], The natural compounds and some models are photosensitive, however [23]. It is this photosensitivity that delayed the discovery of the coenzymes, leading instead to the isolation and characterization of the vitamin [1]. 

Mechanism (1), first suggested almost three decades ago [150], continues to be the most invoked explanation of the role of the enzyme in promoting homolysis. Cleavage of the C—Co bond of sterically hindered alkylcobalamins (e.g., neopentylcobalamin) was markedly increased by diol dehydrase [72], Such cobal-amins do not function as coenzymes but convert to enzyme-bound hydroxocobal-amin in stoichiometric first-order reactions. The strong competitive inhibition by AdoB 12 indicates that labilization occurs at the active site of the enzyme and is suggested to be caused by a steric distortion of the corrin ring. 

Co-C bond weakening and homolysis is induced by interaction of the coenzyme with the enzyme (e.g., through frans-axial ligand substitution or conformational distortion of the corrin ring). 

Various vitamin B12 derivatives are shown in Figure 6.2, where the R group is usually taken as CN-. This form of vitamin B12 is cyanocobalamin. In the active coenzyme, the CN" is replaced by a 5 -deoxyriboadenosyl residue or by -CH3. Vitamin B12 seems to be the only mammalian substance that contains cobalt. It also has a unique corrin ring structure, which is very similar to that of heme. Metabolic reactions requiring vitamin B12 are discussed in Chapters 19 and 20. 

FIGURE 2. Structure of adenosylcobalamin (coenzyme B12 ). Carbons ln20 of the corrin ring are labeled, as are the four pyrroles (AiiD) and the corrin side chains (ang). The a-face lies below the plane of the corrin ring and the p-face above. 

Dong, S. L., Padmakumar, R., Maiti, N., Baneqee, R., and Spiro, T. G., 1998, Resonance raman spectra show that coenzyme B12 binding to methylmalonyl-coenzyme A mutase changes the corrin ring conformation but leaves the C06C bond essentially unaffected. J. Am. Chem. Soc. 120 994799948. 

The various photochemical studies of these compounds have been conducted primarily because of the interest of researchers in the synthesis, properties, and biological activity of vitamin and its derivatives. The structure of vitamin Bj2, as determined by Crowfoot-Hodgkin et al. 109), is shown in Fig. 2. It consists of cobalt in a corrin ring complexed axially by an a-S, 6-dimethylbenzimidazole nucleotide and by cyanide ion. Replacement of the axial CN by a methyl group gives methylcobalamin, and by 5 -deoxyadenosine gives coenzyme Bj2. The formal oxidation state of... 

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