The organic chemistry of biological pathways

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John McMurry and Tadhg Begley, Roberts and Company, Englewood, Colorado (http://www.roberts-publishers.com), 2005, xxxi + 490 pp., price £35.00, ISBN: 0-9747077-1-6This is an interesting book which aims to describe the major biochemical pathways in terms of mechanistic organic chemistry. Its objective is to build a bridge between biochemistry and mechanistic organic chemistry. It is written for advanced undergraduates and graduate students studying biological chemistry and it assumes a good knowledge of organic reaction mechanisms.

The book begins with two general chapters involving, in the first, a review of the organic reaction mechanisms found in biochemical pathways, and in the second a general introduction to chirality and to the structures of important biomolecules. The central part of the book involves chapters devoted to the major metabolic pathways of primary metabolism involving lipids, carbohydrates, amino acids and nucleotides. There is a brief description of some natural product biosyntheses including those of penicillin, morphine, the prostaglandins, erythromycin and vitamin B₁₂. The book concludes with a chapter summarizing the major biochemical transformations and bringing together some of the salient points of the earlier chapters. The pattern of each chapter is to present the overall pathway in a figure and then to describe the mechanism of each individual step. Apart from the natural product chapter, the catabolism of each of the major groups of substances is described before their biosynthesis. Each of the chapters conclude with a list of recent references to the current literature, many of which are post-2000. There are also sets of problems, the answers to which are given at the end of the book. The reader is encouraged to download the structures of various enzymes from Protein Data Base, and there is an appendix giving instructions on how to do this. A second appendix deals accessing with the KEGG and BRENDA databases, which contain information on genes, genomes and specific enzymes. The explanations of the mechanisms are clear, and they are aided by multi-coloured reaction schemes to illustrate the key steps including their stereochemistry. There are helpful cross-references between the discussions of different pathways.

In writing a textbook at this level it is difficult to decide what to include and what to leave out. Inevitably there are likely to be different views on this. For example, the authors do not describe much of the experimental evidence for the particular steps. There is a logic in working with enzyme chemistry particularly in elucidating the stereochemistry of particular steps. A student who thinks about a pathway may realise that there are several plausible mechanisms. A great deal of elegant organic chemistry has been used to distinguish between these various possibilities, and there is much to be learnt from this reasoning. Students also need to know something of the effort that has to be made to establish particular features of a pathway. Biogenetic speculation has played an important role in the design of biosynthetic experiments to test mechanisms, for example in the biosynthesis of morphine. It is pity that some of this is not discussed. A number of biosynthetic steps are the target for drugs. Apart from the intrinsic interest that this generates for students, it can also show a relevance for an understanding of the organic chemistry of these pathways. For example, a discussion of the biosynthesis of the nucleic acid bases without mention of cancer chemotherapy or anti-viral agents, or of prostaglandin biosynthesis without a mention of aspirin, misses valuable teaching opportunities. Errors of metabolism such as phenylketonuria are not mentioned, although the catabolism of phenylalanine is dealt with in detail. In many of these cases a single sentence would serve to enhance the book.

In conclusion, this is an interesting and useful book which should play a helpful role in the teaching of biochemical pathways in a mechanistic sense, providing students with a better understanding of the sequences and interconversions found in biology.

James R. Hanson
Department of Chemistry, University of Sussex, Brighton, Sussex, UK BNl 9QJ

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