Cobinamide coenzyme

Vitamin Bu coenzymes, Ann. N.Y. Acad, Set. 112, 547-921 (1964). I. Chemistry, chemical synthesis and biosynthesis of corrin coenzymes II. Enzymic roles of cobinamide coenzymes III. B 12-coenzymes in micro-organisms and animals. 

Fig. 29. Decrease in intensity of nitroxide ESR signal npon addition of deuterated ethanolamine to ethanolamine ammonia lyase containing spin labeled cobinamide coenzyme. The two curves are for different concentrations of coenzyme to enzyme. The arrows indicate the point at which alcohol dehydrogenase and NADH was added to remove acetaldehyde from the enzyme. Note that full intensity is regained...

A difference in the solid state and solution conformation of 5 -de-oxyadenosylcobinamide (cobinamide coenzyme) has been inferred from the NMR spectrum of cobinamide coenzyme 123) which indicates that the resonance due to the proton at carbon R-l of the ribose is shifted significantly upfield from its expected position. Such an upfield shift would probably have to arise from the ring current of the adenine ring. 

Coa (Lower) Ligand. Cobinamide coenzyme, which lacks the nucleotide loop, was found to be partially active as a coenzyme (26). This indicates that the nucleotide portion in the Coa axial position does not participate directly in the catalysis. The relatively high Km value (6fiM) for this analog suggests the important contribution of interactions at the nucleotide portion to the tight binding of the normal coenzyme. 

The vitamin B12 and related coenzymes (cobalamins, cobinamides, and corrinoids) have been studied in detail using H and shift and relaxation studies. (595-598) With the aid of lanthanide probes the eonformations of cobalamins in solution are shown to be very similar to those in the crystalline state. The appreciable temperature dependences of the electronic and H NMR spectra are attributed to a conformational change rather than to a 6-eoordinate-5-coordinate equilibrium as previously suggested. (599) The binding of 5 -ATP to the respiratory protein hemoeyanin has been studied by H and NMR. 

A separate pathway has evolved to build a-ribazole 84, unusual both in its base, 5,6-dimethylbenzimidazole, and in the a-linkage to ribose. Either a-ribazole 84 or its 5 -phosphate 85 is able to accept the adenosylcobinamide phosphate residue from adenosyl-GDP-cobinamide 83, a transfer catalysed by CobV, to form adenosylcobalamin (coenzyme B12, 4) or its 5 -phosphate, respectively. Dephosphorylation of the 5 -phosphate then leads to 4. Thus the end product from nature s marathon, coenzyme 4, has been reached, a structure of marvellous architecture and amazing biological activity. 

It is not known if all archaea contain adenylated corrinoids or not, however, because most archaea contain a corrinoid adenosyl transferase (CobA) orthologue it is presumed that the corrin biosynthetic intermediates are adenylated. The archaeal ATP Co(I)rrinoid adenosyltransferase from M. mazei strain Gol has been cloned and characterized. Unlike the bacterial enzyme, the M. mazei CobA was found to prefer cobalamin as a substrate over cobinamide, have increased selectivity for ATP over other nucleotides, and was able to utilize 2-deoxynucleotides (dCTP) as well as ribonucleotides. " As it is the methylated form of cobalamin, not the adenylated form, that is involved in methanogenesis, a possible role of the adenylated form of the coenzyme has not been determined. 

A characteristic reactivity of coenzyme B12 (2) in organometallic reactions is the ease of its homolytic decomposition to a 5 -deoxyadenosyl radical and cob(II)alamin (5) (Fig. 6) (26,28). From kinetic analyses of thermal decomposition reactions in solution, the homolytic bond dissociation energies of the (Co-C)-bond of 2 and 3 have been estimated as about 30 and 37 kcal mol" respectively (26,28). Accordingly, the (Co-C)-bond of 3 is considerably more resistant against homolysis than that of 2. At 110°, the thermolysis of adenosyl-cobinamide (8+) in aqueous solution occurs at only a 20 times lower rate than that of the coenzyme 2 (28). Thus, the nucleotide coordination contributes little in activating the... 

Co-C)-bond of coenzyme B12 (2) toward homolysis. Indeed, from thermodynamic data concerning 2 and its homolysis product cob(II)alamin (5), the (Co-C)-bond of the cobinamide 8+ was suggested to be only about 1 kcal mol stronger than that of coenzyme B12 (2) (18,32). 

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