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In general, this book provides a solid substrate complex interacts with the enzyme are heavily stressed. The added com- grounding in the practical and theoretical plexities that occur when a metal activator aspects of enzyme kinetics. The author is plays a dual role in binding to the enzyme careful to point out the limitations of the and the substrate are, however, ignored. various methods discussed and the added This book differs from most works on complexities that can occur if isomerizathis subject in that a considerable amount tions or abortive complex formation takes of space is devoted to practical details. In place. Anyone wishing to learn about the these sections, on the design and conduct subject should benefit from reading this of kinetic experiments, the author provides book, but I feel that the benefit might have a great deal of sound advice which could been greater if the author had developed be read with advantage by anyone starting the principles instead of concentrating on kinetic work. The author's interest in pure the particular. KEITH TIPTON kinetics is, however, evident, since his discussions on the choice of assay conditions Keith Tipton is Lecturer in Biochemistry at the Univercontain no suggestion that there might be sity of Cambridge. Cambridge. U.K. some advantage in trying to approximate these to the conditions that might be expected within the cell. The discussion of the theory of kinetic Alcohol a n d A b n o r m a l Protein Bioanalysis is extremely comprehensive. All synthesis. Biochemical a n d Clinical likely two- and three-substrate reaction edited by M.A. Rothschild, M. Oratz and S.S. Schreiber, published by Pergamon mechanisms are considered and the complete kinetic equations are listed for many Press, New York. $25.-/$10.50 (hard case) (xvff+ 519 pages) of them in an appendix. The types of inhibition given by substrates, products, alternative substrates and alternative products This book is a collection of 24 separate are tabulated for all the mechanisms as essays, each from a different authorship, are the Haldane and Dalziel relationships. bearing on problems relating to the effects In concentrating on this array of particular of alcohol and/or nutritional factors (espemechanisms many of the general principles cially malnutrition) on protein metabolism underlying the analyses are too easily lost. and protein synthesis. The title does not In the section on dead-end inhibitors the do full justice to the contents. About half author lists Cleland's rules and briefly sug- the papers deal with general aspects of proT . H . PENNINGTON gests that they may be understood from tein metabolism, such as methods of investigation, the biochemistry and pathology T.H. Pennington is Senior Lecturer at the b~stitute a consideration of the various pathways of Virology, University of Glasgow, Glasgow, U.K. in which each of the intermediates in the of tissue proteins, and protein transport reaction mechanism may be formed. This through membranes. The quality of the articles, as is not unimportant concept is not developed further, however, and indeed it is not men- usual in multi-author volumes, is uneven. tioned in the discussion of product inhibi- Some of the essays are like chapters of advanced text-books, merely repeating intion. Initial Rate Enzyme Kinetics Cleland's formulation is used for repre- formation already published in previous by H.J. Fromm, published by Sprhzger senting kinetic reaction pathways except reviews, while other authors approach Verlag, Berlin-Heidelberg-New York. in the many instances when this proves their task in a more original manner and to be inadequate, leading to a rather con- offer new and interesting vistas. The reDM78.- ($32.-) (321 pages) fusing mixture of presentations. Occa- viewer found the chapters on the regulaThe presentation of enzyme kinetic theory sionally symbols are not defined when they tion of protein synthesis in relation to in an easily digestible form has always been are first used and there is no general table amino acid supply (H.N. Munro); on a difficult problem, and the solutions that of symbols. The printing is sometimes un- metabolic adaptation to protein deficiency have been adopted by different writers clear and there are a few confusing printing (J. C. Waterlow); on effects of ethanol on range from the strictly mathematical errors. In his choice of illustrative exam- intestinal amino acid transport (Tsun approach to the formulation of qualitative ples the author relies heavily on his own Chang); on diet and protein metabolism 'rules' to enable the kinetic mechanism published work particularly with hexok- in skeletal muscle (D.J. Millward); and obeyed by an enzyme to be deduced with inase. For example, the behaviour of hex- on the control of protein turnover in the the minimum of thought. This book, okinase is used to explain the artefacts that isolated perfused rat heart, of special which is based on a graduate course taught may arise when a metal-substrate complex value. Morphological sections deal with by the author, takes a path between these interacts with the enzyme, in preference changes produced by ethanol, in cardiac two extremes. The material covered is res- to any of the earlier work on such systems. muscle and liver. Rosenoer discusses the tricted to initial-rate and isotope-exchange The book contains details of two useful nutritional potential of enterohepatically kinetics, there being no general treatment computer programs as an appendix, one recycled urea nitrogen in man. Other of the kinetics of transient states. The for deriving steady-state equations a n d chapters deal with alcoholic diseases of the choice of topics is occasionally somewhat one for the statistical treatment of kinetic cardiovascular system, liver and brain. arbitrary, for example the kinetics of acti- data. It is a pity, however, that the latter There is a chapter by H.O. Conn on the vators are not considered in any detail but program is in a language that is not at therapy of alcoholic liver disease. the problems that can arise when a metal- present widely available. Although quite a few of the topics have

of Chapter IIl that only oncorna-, rea-, and poxviruses possess virion-associated transcriptases. I disagree with the interpretation of the antipoxvirus effects of rifampicin in Chapter VII; most workers are agreed that the macrocyclic ring is necessary for activity and that the active site does not reside in the hydrazone side chain. In addition, Becker states that the inhibition of virus envelope formation follows the inhibition of cleavage of a structural polypeptide precursor, whereas the experimental evidence in fact suggests the reverse. The statement in Table III that rifampicin inhibits poxvirus coat protein synthesis has possibly crept in as an oversimplification, synthesis being substituted unintentionally for processing. With the exception of these criticisms and one or two other over-simplifications and omissions, the monograph presents a concise and accurate account of inhibitors of animal virus growth, and will serve as a useful review of this subject. The lengthy interval between the completion of the literature survey and the publication date means that the book is already somewhat out of date. As is usual with Karger, the book is well produced; an innovation for the 'Monographs in Virology' series is the soft cover. Unfortunately this has not had any inhibitory effect on the now-to-beexpected high price.

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been reviewed elsewhere, investigators interested in the pathology of alcohol and in nutrition may find it useful to have a variety of aspects assembled in one volume. H . A . KREBS

H.A. Krebs is Emeritus Pro/bssor of Biochemistry at O.xford Universio,, O.~ford, U.K.

Valuable protein guide Chemical Modification of Proteins by A.N. Glazer, R.J. Delange and D.S. Sigman, published by North-Holland, Amsterdam~American Elsevier, New York. 1975. Dfl.28.- ($11.75) (205pages) This pocket-edition of a very successful volume in a larger series is in itself a comprehensive treatise of the important topic of protein labeling by modification. Auxiliary and basic methods of protein chemistry take up the first third of the book. This includes a very thorough chapter on amino acid analysis, comprising practically all of the available data on modified amino acids. Even for a specialist in the field it would probably be difficult to gather all the information on enzymatic hydrolysis of proteins, or identification of naturally modified amino acids given here. Bravely, the final articles of this chapter also dip into the dark field of glycoprotein analysis. And with good success, too, as they are wisely restricted to the firm ground of well established methods, furnishing a solid basis for any protein chemist who might find himself forced to venture out into glycoproteins. The second part of the book is taken up with the various amino acid side chains in proteins amenable to chemical modification, and with the many reagents that have been used for this purpose. Again, the book admirably discerns between the more frequent techniques, which may be taken up by research specialists from other fields without trepidation, and the more exotic methods that need some experience in modification. Experimental details and more important the possible pitfalls in the evaluation of side-chain modifications by groups-specific reagents are described. The comprehensive description of enzyme kinetics, and their use for analysis of the success of enzyme modifications serves to show up the dangers of this kind of 'nonspecific' reagent. In the last third of the book, the modification by site-specific labels is described, this being probably the most frequent goal in protein chemistry today. Perhaps it would have been an easy sideline to include a chapter on affinity isolation techniques at this point, although the theme would not be quite in keeping with the subject

of the book. The advantages of affinity labels are discussed, and a number of very useful examples brought forth. Since the syntheses of substrate analogues for the purpose of protein labeling follow so many different avenues, only the most commonly used pathways are given in a final chapter as synthetic procedures, but one will find that these already cover a large number of the pseudosubstrates proposed so far. The book is designed for scientists already working in the field, as well as for those who want to get a grasp of the techniques of protein modification new to them. Both will find it a valuable guide and a thorough review of the literature available on the subject. It contains a surprising amount of information in so small a volume, and the procedures in question are quickly and easily found. H. FASOLD

H. FasoM is Professor of Biochemistry and head ol the b~stitute for Biochemistry at the Johann Wolfgang Goethe University, Fran,~fitrt. G.F.R.

Clear opiate account Opiate Receptor Mechanisms edited by S.H. Snyder and S. Matthyssee, published by M.I.T. Press, London £4.95 (vi+ 166 pages). Opiates have been used by man for many centuries, but the mechanisms underlying their action on behaviour has not been understood until recently. Opiates relieve chronic pain, and may promote feelings of relaxation. This euphoric effect is instrumental in their continued use by some individuals, leading to severe consequences: addiction involving usually both physical and psychological dependence on the drugs, while severe symptoms are precipitated when the opiates are withdrawn. Because of important new discoveries on opiate action in the nervous system the Neurosciences Research Programme sponsored by the Massachusetts Institute of Technology organized a Work Session to review new developments, and the proceedings of this multidisciplinary meeting are presented in this exciting little book. Often it is rather irritating to read a second-hand account of the work of individual research groups, but this book, in the spirit of other publications in this series, is a veritable exception. The editors have made an extremely good job of presenting the contributions, which encompass virtually all the major disciplines in neurosciences, in a condensed and lucid way. The result is that, in spite of the otherwise demanding background knowledge, the non-expert reader is guided through sophisticated chapters and is able to

assimilate detailed information without losing sight of the major problems in the search for the better understanding of opiate action in the brain. It is a great additional achievement that in spite of the unavoidable abbreviation of the proceedings the editing has not removed controversial questions, while problems which do not fit the hypotheses presented are also emphasized. An extremely important development reported at the session was the recent progress in the understanding of the interaction of opiates with their recognition sites. Three groups, Simon's from New York, Snyder's from Baltimore and Terenius's from Uppsala, discovered simultaneously and independently the stereo-specific, high-affinity binding of opiate agonists and antagonists to brain tissue. The circumstantial evidence presented is convincing in identifying the binding sites in the tissue as opiate receptors. Good correlations are found between pharmacological potencies of the various drugs and their binding properties, and between the effective analgesic sites in the brain and the areas rich in opiate binding activity. Some of the pitfalls are also mentioned; for example, it seems that some of the drugs are stereospecifically bound to glass fibre filters and that cerebroside sulphates exhibit high affinity binding properties. It is also refreshing that the controversy between the groups of Snyder and Simon in the interpretation of the effect of Na + in enhancing antagonist binding is given. The recognition of the existence of opiate receptors has led to the formulation ofthe hypothesis that these receptors form a part of a neuronal system that functions through the mediation of a naturally occurring 'morphine-like' compound. An endogenous ligand was indeed discovered independently by Hughes and Terenius. Extensive studies conducted before and after the Work Session also in the laboratories of Snyder and Goldstein have borne fruit: it has been established that the endogenous ligand(s) compete effectively with opiates for the binding sites in vitro, that they have potent agonist activity at the opiate receptors in vivo and that their action is completely blocked by morphine antagonists. Furthermore, their distribution in the brain more or less parallels that of the opiate receptor. The study of one of the endogenous ligands has recently reached the stage of chemical characterization (Hughes et al. (1975) Nature 258, 577): enkephalin is a mixture of two pentapeptides which only differ in the C-terminal amino acid. It seems that the critical amino acid sequence is also present in other endogenous peptides and that structural similarities exist with fl-melanotropin and cor-