Chemical Education Today edited by
Book & Media Reviews
Jeffrey Kovac University of Tennessee Knoxville, TN 37996-1600
The Organic Chemistry of Biological Pathways by John E. McMurry and Tadhg P. Begley Roberts & Co.: Englewood, Colorado, 2005. 490 pp. ISBN 0974707716 (cloth). $92 reviewed by Alan M. Rosan
This modern, comprehensive, dense, and beautifully presented book has one goal: to make explicit the mechanistic organic chemistry underlying fundamental biochemical pathways. In this effort it succeeds admirably. An authoritative text set in eight chapters (from 19–168 pages each), The Organic Chemistry of Biological Pathways begins with a condensed overview of the principles and tools required to understand reaction mechanisms followed by a brisk survey of the structure, stereochemistry, acid–base properties, energetics, and biological function of biomolecules. Reading like primers of organic chemistry and biochemistry, these first two chapters set the stage for the smart and expertly delivered exposition to follow. To be sure, this book definitely requires a thorough grounding in the language and symbols used to depict organic reaction mechanisms but it will substantially reward the reader. Chapters three through six deal with the metabolism of the four major classes of biomolecules, lipids, carbohydrates, amino acids, and nucleotides. Each opens with a discussion of degradative pathways and concludes with biosynthetic avenues. These are followed by a marvelously insightful discussion of the biosynthesis of some selected natural products, the penicillins and cephalosporins, morphine, the prostaglandins and eicosanoids, erythromycin, and coenzyme B12 and related tetrapyrroles, all chosen to emphasize nature’s arsenal of construction and functionalization processes. The book ends with a concise and lucid 19-page summary of biological transformations. This concluding chapter, like the entire text, is organized around metabolic pathways and attendant reactions (not structural or mechanistic motifs) and it nicely returns to the central theme of biochemical transformation as organic chemistry as exemplified by, for example, acyl transfers, carbonyl condensations, addition and release of CO2, transfer of single carbon units, amination/deamination, rearrangements and various redox, oxidation, and hydroxylation reactions. Having chosen to organize this presentation on the basis of metabolic pathways, the authors concentrate on the use of common and repetitive mechanistic themes even among diverse processes. I found this an excellent and effective pedagogy leading to an insightful appreciation of the patterns of mechanistic logic nature employs to accomplish various metabolic and biosynthetic tasks. Although the book is decidedly focused on the organic chemistry of life, the importance of cofactors and metalloenzymes is not neglected. Indeed, in an
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exceedingly clear discussion the authors explain how and why the iron–oxo family of intermediates, central to electron transfer and oxidative transformations, is utilized in myriad biochemical redox processes. Conversational, professional, and crystal clear, this text aims to examine biological transformations from an organic chemical perspective. The authors use vivid schemes and crisp drawings on virtually every (and I mean every) page, color coded to accentuate electron flow and reaction mechanism, to provide an authoritative examination of the major biochemical pathways for metabolism, catabolism, and biosynthesis. The juxtaposition of the often extended mechanistic schemes with accompanying definitive explication, often on the facing page, with each step numbered, makes the discussion easy to follow. The approach here is to first give a summary outline of a pathway and then provide, in a play-by-play explanation of each step, the exquisite mechanistic detail highlighting important features and subtleties. Sometimes pathways are condensed in that a reaction product is shown already engaged with the next substrate or enzyme. The more I delved into this text the more I experienced biological pathways as recipes and mechanisms as an interplay of ingredients. Emphasizing that biological chemistry utilizes common themes, the authors consistently direct the reader to previous sections and cite prior examples to reinforce mechanistic parallels. Major assets of this text are the up-to-date references provided in chapters three through seven, including leading citations to the primary literature up to 2004 (from 28 to 56 citations per chapter). Each chapter, except the last, which is summative, concludes with quite challenging problems (from 9 to 22) for which solutions are provided in Appendix C. Other appendices provide explicit instructions for using the online Swiss Protein Data Bank (PDB) viewer (which offers access to the 3-D structures of 25,000 proteins) (1) as exemplified by the specific example of alcohol dehydrogenase; the Kyoto Encyclopedia of Genes (KEGG) (2); and the BRENDA (3) data bases. A set of problems augments the usefulness of the section on the PDB. The importance of teaching these modern resource tools is perhaps recognized by the recent use of the BRENDA data base in support of a controversial interpretation of enzyme proficiency (4). The book also provides a listing of 87 abbreviations and a 14page index. Those conversant with McMurry’s other fine texts will find here a familiar tone and authenticity. The text is virtually free of errors of any kind (I found only one substantive error in a problem in chapter 7). My main comment is that this is a high-level book that demands a working familiarity with basic concepts of structure, chirality, acidity, potential energy, arrow movement, and the like. One small suggestion would be to have used stereo arrows to illustrate attack at chiral faces. I would emphasize that this text distills the essence of biochemical pathways, delivering mechanistic insight with encyclope-
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Chemical Education Today
Book & Media Reviews dic authority. In presenting contemporary knowledge and results, it does not emphasize how this information was obtained, and it does not ask one to suggest experiments meant to answer additional mechanistic questions. By providing leading references, it instead leaves to the interested reader the task of examining the experimental protocols that provide the mechanistic insight that is described. While some students might be tempted to conclude from this presentation that most, if not all, details of biochemical pathways have already been elucidated, I was pleased that the authors did indicate that much remains, citing the recently discovered and poorly understood deoxyxylulose (DXP) pathway by which isopentenyl diphosphate can be biosynthesized. In conclusion, this definitive book is not a substitute for a biochemistry textbook but would be exceedingly useful as an ancillary resource in an upper-level biochemistry or bioorganic chemistry course. Alternatively, it could serve admirably as a stand alone text on the chemistry behind biological transformations and would certainly serve the advanced undergradu-
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ate or scholar as a reference in a variety of contexts. It is a text to which I plan to turn repeatedly for insight into the vibrant interface between organic reaction processes and the fascinating world of biochemical transformations. Literature Cited 1. The Swiss Protein Data Bank viewer is at http://www.rcsb.org/ pdb/ and http://swissmodel.expasy.org/spdbv/ (accessed Aug 2005). 2. The Kyoto Encyclopedia of Genes is at http://www.genome. ad.jp/kegg (accessed Aug 2005). 3. The BRENDA data base is at http://www.brenda.uni-koeln.de/ (accessed Aug 2005). 4. Zhang, X.; Houk, K. N. Why Enzymes Are Proficient Catalysts. Acc. Chem. Res. 2005, 38 (5), 379–385.
Alan M. Rosan is in the Department of Chemistry, Drew University, Madison, NJ 07940;
[email protected].
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