TIBS 18 - SEPTEMBER 1993

BOOKREVIEWS

Lehninger lives on Principles of Biochemistry (2nd edn) by A. L. Lehelnger, D. I.. Nelson and M. M. Cox, Worth Publishers, 1992. £30.00 (xli + 1013 pages) ISBN 0 87901 500 4

Like Professors Nelson and Cox, who are responsible for this new edition, I remember the appearance of Lehninger's Biochemistry in 1970 as marking the birth of the modern, comprehensive, biochemistry tex~tiJook. Not for us later upstarts like Stryer and the rest - the master had written and, at least until well into the 1980s, the others were merely pale imitations.

What was so revolutionary? Colour was introduced but, even in the 1982 revised version, Principles of Biechemistry, there was only one colour apart from black. There were didactic diagrams, but surpl'isingly few compared to formulae and reaction schemes. Perhaps the boldest stroke was the introduction of a wide margin, about one-third of the page across, in which formulae, diagrams and figure legends could be sited without breaking up the flow of text. This surprisingly simple device greatly aided clarity and accessibility and has been widely copied in later biochemistry (biology and chemistry) texts; it Is retained in the present volume.

Nelson and Cox argue that the primary contribution of Lehninger to present-day texts was not the spatial but the intellectual organization. It is difficult to imagine a text today without the higher- order structure of 'Physicochemical Principles', 'Molecular Structure', 'Bioenergetics and Metabolism', and 'Informational Aspects', with component chapters, in Section 2 for example, on amino acids and peptides, protein structure, enzymes and catalysis, lipids, membranes, carbohydrates, etc. This organization, even down to the same order of chapters, is almost invariably found in present-day texts.

Lehninger himself tried to modify this organization by including a central section on 'Aspects of Human Biochemistry' in the first edition of Principles of Biochemistry but this is not present in the new edition. The other modern biochemistry text that attempted to break the mould, by Metzler, was never revised, although it lives on as the origin of that other now universal device, the 'Box' for information peripheral to (more interesting than?) the main text.

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Chapter organization, page layout, boxes - all are retained in the present volume. Most of the problems, too, are taken from the first edition. What, then, is new? Clearly, the information has been updated very successfully. The text records the role of glycogenin and details of ribozyme action, for example, and explains the action o! present-day drugs such as cimetidine, tamoxifen and suicide substrates. References are cited up to 1992. Obviously, too, the use of colour is more lavish. This is generally effective. I was impressed not so much by the use of colour in illustrating protein structures, DNA replication, etc. - this is done well, but it is also found in other texts - but its use in the treatment of metabolic interrelationships and, particularly, intracellular compartmentation. I may be biased, but it also encourages me to find, at last, (a) photophosphorylation covered together with oxidative phosphorylation, and carbon fixation with the pentose phosphate shunt, and (b) carbon being exported from chloroplasts as triose phosphate! Even minor revisions are well considered; it is surprising how much easier it is to follow the C 4 pathway for CO 2 fixation when it is depicted in a clockwise direction as here, rather than anticlockwise (as previously). The one aberration is the depiction of the chymotrypsin mechanism, which is too small and obscured by a variable blue background.

Other features that distinguish this text from its various competitors are the use of small photographs of space-filling models of protein structure (apparently created by Alisa Zapp- David Lodge, please note) and of notable biochemists [Maud Menten, Hans Krebs, Francis Crick (twice), etc. - but no Ed Southern]. However, these illustrations have limited value as teaching devices. The space-filling models suggest little more than that proteins are large and

complicated, and the personalities, while they make an impressive archive, suggest little more to the student than that biochemists are largely white, male and wear neckties. Space-filling models are instructive when accompanied by corresponding ribbon diagrams and expansion of active/binding sites - and the authors do utilize this comparison to great effect in a few instances - but their use elsewhere is questionable.

All in all, this is a well designed and well executed biochemistry text, which ! would recommend to undergraduate students. It is certainly as good as, and in places better than, competing texts. Parts are very impressive - 1 enjoyed the clear expositions of transition state theory, of the techniques involved in protein and DNA manipulations, and of the mechanisms of gene regulation, for example. Other parts are not - the impression is given that intracellular ATP is an important regulator in metabolism, and that 'futile cycles' are indeed futile. There are few errors (although VHDL, 'very high density lipoproteins' make a brief appearance) or aberrations (blood glucose is given in mg/lO0 mL). The references are well chosen, generally recent reviews, not too many (so that the student is not overwhelmed) and helpfully annotated.

One nagging worry remains, Why is this book called Princiales of Biochemistry? It has a broad coverage both figuratively and literally- it is 4 cm wider than Lehnlnger's original Biochemistry. Do biochemists really have 1100 pages of principles? Is it a marketing ploy? If so, I hope it won't backfire and limit the audience - the book deserves a wide readership.

D. A. HARRIS

Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK OXl 3QU.

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TIBS 1 8 - SEPTEMBER 1993

Going all the way

Viral Fusion Mechanisms

edited by Joe Bentz, CRC Press, 1993. $199.95 (529 pages) ISBN 0 8493 5606 7

If the last stages of personal contact are complicated and lead to irrevocable changes, those of an enveloped virus with its targeted host are no less so. The problem is simple: how to mix the hydrophilic contents of two compartments when each is isolated within a hydrophobic membrane. But the simplicity of the problem belies a complexity of mechanism that is only now bcginning to be unravelled.

That viruses can cause membrane fusion has been known for many years, and the dogma found in older textbooks was that once a virus docked with a cell, via a receptor, it was close enough for the water molecules between the two to be excluded and for membrane coalescence to occur spontaneously. But this is a long way from the truth - in the case of influenza virus about 100 angstroms away to be precise. In order to dock with target cells, viruses have evolved complex surface proteins (the virion spikes) that stand out from the membrane in order to catch the virion receptor efficiently. For the purpose of the initial docking event this is clearly advantageous but it leaves the virus out on a limb (literally) as far as the fusion of membranes is concerned. Whether out on the plasma membrane surface or following internalization of the receptor-virion complex, some form of receptor-spike collapse or removal must occur If the virus is to get close enough for the formal fusion event. Our current state of knowledge of these events, particularly the conformaUonal changes required before fusion can he initiated, are covered in this comprehensive and timely book.

A collection of single chapters written by authors active in the field of viral fusion, this book covers the predictable (though clearly unomitable) influenza virus fusion reaction in the greatest detail and there are also two chapters each devoted to Sendal virus fusion and the HW gpl20--CD4 interaction. For sales per unit page many publishers would have stopped at that; two examples of fusion reactions where much is known and one where, perhap~ most practical benefit from a knowledge of the molecular requirements of fusion is to be gained. Pleasingly, however, the scope of this book has been widened to cover several other virus models (Herpes, Vaccinia, Sinbis, VSV and RSV) and also includes chapters on the techniques commonly

used in the study of membrane movement (fluorescence dequenching, for example) and membrane architecture (cryoelectron microscopy). Chapters on the theory of fusion complete the book. Bentz explains the organization of the book in the first few pages and had me convinced of its logic even before I waded through the full text. Having done so, however, I can vindicate his planning and can honestly say that I learned a great deal. From the breadth of coverage one can glimpse the varied mechanisms adopted by viruses to achieve the final goal. For example, many viruses encode a single protein that is both necessary and sufficient for fusion. By contrast, both Herpes and Vaccinia, big complex DNA viruses with the room to carry baggage, appear to have a correspondingly complex requirement for fusion proteins. A number of viruses, influenza being the most well known, make use of the endosomal processing pathway to acidify the fusion protein and trigger its action. Others, like HIV, can apparently do it all at pH 7.0 once receptor binding has triggered the process. This is possible despite the fact that HIV has a glycoprotein that is not much bigger (or more complex?) than the 'flu glycoprotein, although it should be added that the evidence for secondary receptors playing a role in HIV fusion is strong if still a bit nebulous. The fusion proteins themselves are also varied. In the case of the 'flu glycoprotein the receptor binding and fusion activities are subdomains within one molecule and are connected by a disulphide bond. HIV has a similar arrangement but the two domains are not covalently linked and can be separated, although whether this is a necessity [or, or a consequence of, fusion is still not clear. Viruses such as Sendal and RSV separate the activities from the beginning, having distinct glycoproteins for receptor binding and fusion activity, and one is left wondering which came first. Have separate functions evolved from a single molecule via a split- domain intermediate or vice versa? In

fact, this book has left me with a level of bewilderment about a whole number of related fusion issues - a compliment, I think, to the authors who have all written open discussion-type chapters that spell out what is not known as clearly as what is.

The book is a wealth of information that is great for dipping into (the reference lists alone provide a mini bibliography on viral fusion) but it also provides a continuity in subject area that is likely to keep it at the front of the reference shelves for many years. Faults are generally hard to find. The typesetting and quality of the book are both very high but I was a bit disappointed with the diagrams, all of which are cartoon style. Ribbon diagrams, for example, of proposed three-dimensional structures leave the reader trying to trace a pencil along the ribbon in order to determine whether a strand is over or under another that it crosses.

My one other suggestion would be that publishers consider releasing a copy of a book like this on disk along with the printed copy 0nside the back cover, for example). Given that a reference book of this type contains the majority of points and bibliography lists that interested readers are likely to need for their own work, it would be very convenient to be able to search the book on screen and copy references of interest directly to manuscripts or notes. This, I suspect, would be an added selling point to tempt buyers.

Notwithstanding these minor problems, this book is easily worthy of that gap on your shelf. It is aimed at active researchers from postgraduate up but its mix of up-to.date review and open speculation would also intrigue the more adventurous undergraduate, with or without a targeted partner.

IAN JONES

Institute of Virology, Mansfield Road, Oxford, UK OXl 3SR.

Rationalizing Vincent

Vincent van Gogh: Chemicals, Crises and Creativity

by Wilfred N. Arnold, Birkh&user, 1992. Sfr. 88.00/£37.20/$49.50 (332 pages) ISBN 0 8716 3616 1

Numerous theories have been proposed to explain creativity, innovation and the factors that contribute to genius. There is no doubt that some of the greatest

geniuses have suffered from mental instability and have exhibited eccentric or extravagant behaviour. Gifted and talented individuals often, apparently unconsciously, create extreme personal experiences to provide the inspiration necessary for artistic expression. A partially disordered mind may even be a prerequisite for the spontaneous mental accidents necessary to generate novel thought. The question arises whether Vincent van Gogh was unstable for medically explicable reasons and that this contributed to his bizarre behaviour and his suicide or whether it was his artistic

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