Cobalamin chemistry

Model studies in nitrogen fixation and cobalamin chemistry Nitrogen-fixing plants... 

Cobalamin chemistry is the best-established area of cobalt biological chemistry. The 15-membered tetraazamacrocyclic corrin ring (incorporating four pyrrole residues) is the binding site for... 

Model Studies in Nitrogen Fixation and Cobalamin Chemistry... 

At the time of the first volume of CCC(1987), the biological chemistry of cobalt was almost exclusively concerned with the cobalamins. The field has expanded and developed markedly since then. New cobalt-containing proteins have been characterized and applications of traditional cobalt coordination compounds in biology developed. These developments are illustrated below in some detail, as the field was not reviewed in the first edition. 

Co within all compounds of the so-called cobalamin (or B12) family. The biological functions of cobalamin cofactors are defined by their axial substituents either a methyl or an adenosyl group. Both cofactors participate in biosynthesis the former in methyl transfer reactions while the latter is a free radical initiator, abstracting H atoms from substrates. Decades after their initial characterization, the fascination with the biological chemistry of cobalamins remains.1109... 

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. 

Schumacher, W., C. Holliger, A. J. B. Zehnder, and W. R. Hagen, Redox chemistry of cobalamin and iron-sulfur cofactors in the tetrachloroethene reductase of Dehalobacter restrictus , FEBS Lett., 409, 421-425 (1997). 

The preceding qualitative picture requires further investigation of both the energetics and structural changes in models and cobalamins. However, if it represents a reasonable approximation of the interrelationships among structure, coordination number, and axial bond strengths, then the intermediacy of 5-coordinate ComR species in the enzymatic process involving Co" and radical chemistry of coenzyme B -dependent enzymes appears unlikely. 

Characterization of cobalamin receptor sites in brush-border plasma membranes of the tapeworm Spirometra mansonoides. Journal of Biological Chemistry, 258 4261-5. 

Analogous ring enlargement reactions, including a radical promoted Q incorporation, are known in steroid chemistry Irradiation of the 11/3-nitrite of 4-androstene-ll/3-ol-3,17-dione (VII/59) (Barton reaction) in toluene gave 18-nor-D-homo-4,13(17a)-androstadiene-llj8-ol-3,17-dione (VII/63) [33]. For Q radical rearrangements mediated by cobalamin, see [34] [35] [36] [37]. 

The rich and versatile chemistry of cobalamin has inspired a vast amount of work, both mechanistic and synthetic. The key features is the weakness of the C-Co bond (20-30 kcal mol-1), which upon thermolysis or more commonly photolysis (visible light) gives a carbon radical and a persistent Co(II)-centred radical. 

Chemistry. The cobalamin family consists of a corrin ring (Fig. 8.54). It is similar to that of the porphyrin ring system, except that there is no methylene or methine bridge between p3Trole rings A and D, and it contains cobalt rather than iron. The commercial form sold in the United States is cyanocobalamin. The hydroxy dosage form also has been used. The coenzyme forms include methyl and ad-enosyl cobalamin. The commercial vitamin is produced from bacterial fermentation. 

The chemistry of the cofactors has provided a fertile area of overlap between organic chemistry and biochemistry, and the organic chemistry of the cofactors is now a thoroughly studied area. In contrast, the chemistry of cofactor biosynthesis is still relatively underdeveloped. In this review the biosynthesis of the cofactors shown in Fig. 1 will be described. Heme and cobalamin will be omitted as these are covered in the review by Allan Battersby and Finian Leeper in this volume. We will focus on cofactor biosynthesis in Escherichia coli because the relevant genetics and biochemistry have been most intensively studied in this organism and it is the easiest system in which to carry out molecular biology [1]. Enzymes from other sources will be described only if the corresponding enzyme from E. coli has not been isolated or subjected to mechanistic studies. 

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