- Email: [email protected]
Biophysical and physiological systems analysis
BIOCHEMICAL EDUCATION
BOOK REVIEWS
The Urea
Cycle
E d i t e d by S. Grisolia, R. B a l a g u e n a a n d F. Mayor. Pp. 560. J o h n Wiley a n d Sons, 1976. £22.00 or $37.50. Ammonia has come a long way for an inorganic material which was originally detected in the bouquet from camel deposits in Egyptian temples. In particular, it can be fixed in animal tissues to form urea, which was the first constituent of living organisms to be synthesized both artificially (by Wohler) and also in a tissue preparation. This latter discovery, of the ornithine cycle, was of course made by Sir Hans Krebs, and reported in 1932 in a paper which is one of the classics of this century. Truly an Immaculate Perception. This volume celebrates this discovery, and the work on urea and ammonia metabolism which has ensued. All the major figures who have taken further the understanding of urea and ammonia metabolism are represented. Hence it goes without saying (or almost) that this is an excellent volume, compounded from firstrate chapters, written by leaders in their fields. Sir Hans Krebs himself provides a historical account of the discovery of the ornithine cycle, which illustrates so many points about breakthroughs in science. New techniques were devised (urea measurement, the famous plasma substitute), a big problem was tackled in unblinking fashion, and the answer emerged from the quantitative approach (with the demonstration of the catalytic role of ornithine). All major aspects of urea metabolism are reviewed, including chemistry of urea, comparative and evolutionary aspects, clinical problems (inborn errors, hepatic encephalopathy) and nutritional and developmental responses. Much relevant enzymology is presented, although there is excess articulate activity about carbamoyi - - phosphate synthetase. Indeed one equation includes 24 terms in its apparent denominator, but luckily some doubt was expressed about its relevance in vivo. I mean, how could a rat understand an equation like that? In regard to the argininosuccinate enzymes, the work of Dr. Sarah Rather has cornered the market, and appropriately, her chapter is long and superb. This book is in fact dominated by the magnificent specialist chapters. In addition to those enumerated above, there are articles on some of the topics ancillary to urea metabolism. For example, the properties of glutamate dehydrogenase are reported. (Can this reaction really be at "near-equilibrium" in the light of all the catalytic complexity?) The role of acetyl-giutamate is explored. (Are there any reports of acetyl-aspartate in the liver?) Several facets of hepatic ammonia metabolism are reviewed, including the use of hepatocyte suspensions in the study of histidine metabolism (contributed by the real Hems), and factors affecting intracellular ammonia concentration in liver. Glutamine metabolism is brought up to date by Dr. Patricia Lund, apprositely enough, as several aspects of glutamine metabolism have numbered among Sir Hans Krebs' 173 "other" discoveries. The effects of ethanol on ammonia metabolism are described by Dr. Marion Stubbs. This was late in the symposium, and presumably was followed by voluntary practical classes. (These two chapters also show why Sir Hans Krebs is justly renowned for his clutch of elegant lady colleagues.) For the education of biochemists, this volume will therefore best serve the purpose of advanced nitrogenous workers, as an informative and reference source. It is in effect a textbook of biochemistry, and would grace any library on that account alone. Even the Discussion Sessions are of a high standard. Vanity must be served by delineating a few omissions. Problems of compartmentation are not full brought out. The location of the step featuring aspartate in the extra-mitochondrial phase presumably has to do with other roles of aspartate. In particular, there is a parallel conversion of aspartate to fumarate in the purine
January 1977 Vol. 5 No. 1
19
nucieotide cycle, and the inter-relationships among these reactions are not explored. Metabolism of arginine and citrnlline in other tissues is not fully covered. An old problem concerns the possibility of alternative pathways. (Incidentally, is "alternate" now sanctified as the international version of this word? May we in England protest at the deterioration in our language?) The regulatory function of ornithine is not fully clarified. Finally, it is not explained to this reviewer's satisfaction why the kidney has no urease, as this would be such a useful enzyme (under control of course) in the distal tubule. In summary, most of mammalian urea and ammonia metabolism is encompassed in this book, which is not short. A n exact and fitting comment on Sir Hans Krebs' career, as was intended by the editors, who are to be congratulated. D. A. Hems Department of Biochemistry St George's Hospital Medical School London S.W.17, U.K.
Biophysical and Physlologleal Systems Analysls Erol Basar. Pp. 428. Addison-Wesley Publishing C o m p a n y , Inc. Mass. U S A 1976. Cloth $24.50, p a p e r b a c k $12.50. This book attempts to fill an obvious gap between classical physiology and a mathematical approach to biological problems. It succeeds because the author gives background coverage of the physiological systems under review before discussing the theory of systems analysis. The reader is provided with simple diagrams illustrating the related facts, using only the minimum of mathematical trimmings. Hence it is readily acceptable to students who wish to obtain a working knowledge of the components of behaviour and are interested in their interpretation. The rules and concepts of biological processes are defined as properties relating to the input and output of a given system. Earlier chapters deal with the general principles and classification of systems analysis, giving as examples of Abstract methods the study of transient responses, frequency characteristics and oscillatory behaviour whilst the more conventional procedures of ablation and pharmacological application are cited as Special methods of analysis. Subsequent chapters offer a more detailed application of analytical theory to different biological systems. The subject of circulatory autoregulation is chosen to illustrate mechanisms that do not require continual control by the nervous system. Several hypotheses are described on the intrinsic dynamic properties of smooth muscle to elicit a common causal factor; other examples are taken to illustrate the outputs of non-linear systems in which, however, the reader is expected to have the basic mathematical knowledge applicable to model-experiments. Of particular interest to the neurophysiologist is the section dealing with electrical signals from the brain. This is a fairly comprehensive study ranging from the spontaneous rhythms of large neuronal populations to the evoked potential components arising from various input signals. The dynamics of brain potentials during sleep and the waking state are correlated with samples of structural organization and of selective blocking by drugs. The author points out the value of computational methods of analysis and some of the difficulties encountered, but limits his data processing to selective averaging of the stored recordings. There is no reference to studies of post stimulus time histograms and crosscorrelation functions. It is a pity, also, that these analytical methods have not been applied to single unit discharges. As far as the presentation is concerned, this book can be highly recommended. The concepts and objectives are clearly indicated at each stage and summarized intelligently. The reader may even be stimulated to search further into the intricate transkn'mations of signal coding that are presumably the basis of all behavioural reactions. P. P. N e w m a n
Department of Physiology University of Leeds, U.K.
BOOK REVIEWS
The Urea
Cycle
E d i t e d by S. Grisolia, R. B a l a g u e n a a n d F. Mayor. Pp. 560. J o h n Wiley a n d Sons, 1976. £22.00 or $37.50. Ammonia has come a long way for an inorganic material which was originally detected in the bouquet from camel deposits in Egyptian temples. In particular, it can be fixed in animal tissues to form urea, which was the first constituent of living organisms to be synthesized both artificially (by Wohler) and also in a tissue preparation. This latter discovery, of the ornithine cycle, was of course made by Sir Hans Krebs, and reported in 1932 in a paper which is one of the classics of this century. Truly an Immaculate Perception. This volume celebrates this discovery, and the work on urea and ammonia metabolism which has ensued. All the major figures who have taken further the understanding of urea and ammonia metabolism are represented. Hence it goes without saying (or almost) that this is an excellent volume, compounded from firstrate chapters, written by leaders in their fields. Sir Hans Krebs himself provides a historical account of the discovery of the ornithine cycle, which illustrates so many points about breakthroughs in science. New techniques were devised (urea measurement, the famous plasma substitute), a big problem was tackled in unblinking fashion, and the answer emerged from the quantitative approach (with the demonstration of the catalytic role of ornithine). All major aspects of urea metabolism are reviewed, including chemistry of urea, comparative and evolutionary aspects, clinical problems (inborn errors, hepatic encephalopathy) and nutritional and developmental responses. Much relevant enzymology is presented, although there is excess articulate activity about carbamoyi - - phosphate synthetase. Indeed one equation includes 24 terms in its apparent denominator, but luckily some doubt was expressed about its relevance in vivo. I mean, how could a rat understand an equation like that? In regard to the argininosuccinate enzymes, the work of Dr. Sarah Rather has cornered the market, and appropriately, her chapter is long and superb. This book is in fact dominated by the magnificent specialist chapters. In addition to those enumerated above, there are articles on some of the topics ancillary to urea metabolism. For example, the properties of glutamate dehydrogenase are reported. (Can this reaction really be at "near-equilibrium" in the light of all the catalytic complexity?) The role of acetyl-giutamate is explored. (Are there any reports of acetyl-aspartate in the liver?) Several facets of hepatic ammonia metabolism are reviewed, including the use of hepatocyte suspensions in the study of histidine metabolism (contributed by the real Hems), and factors affecting intracellular ammonia concentration in liver. Glutamine metabolism is brought up to date by Dr. Patricia Lund, apprositely enough, as several aspects of glutamine metabolism have numbered among Sir Hans Krebs' 173 "other" discoveries. The effects of ethanol on ammonia metabolism are described by Dr. Marion Stubbs. This was late in the symposium, and presumably was followed by voluntary practical classes. (These two chapters also show why Sir Hans Krebs is justly renowned for his clutch of elegant lady colleagues.) For the education of biochemists, this volume will therefore best serve the purpose of advanced nitrogenous workers, as an informative and reference source. It is in effect a textbook of biochemistry, and would grace any library on that account alone. Even the Discussion Sessions are of a high standard. Vanity must be served by delineating a few omissions. Problems of compartmentation are not full brought out. The location of the step featuring aspartate in the extra-mitochondrial phase presumably has to do with other roles of aspartate. In particular, there is a parallel conversion of aspartate to fumarate in the purine
January 1977 Vol. 5 No. 1
19
nucieotide cycle, and the inter-relationships among these reactions are not explored. Metabolism of arginine and citrnlline in other tissues is not fully covered. An old problem concerns the possibility of alternative pathways. (Incidentally, is "alternate" now sanctified as the international version of this word? May we in England protest at the deterioration in our language?) The regulatory function of ornithine is not fully clarified. Finally, it is not explained to this reviewer's satisfaction why the kidney has no urease, as this would be such a useful enzyme (under control of course) in the distal tubule. In summary, most of mammalian urea and ammonia metabolism is encompassed in this book, which is not short. A n exact and fitting comment on Sir Hans Krebs' career, as was intended by the editors, who are to be congratulated. D. A. Hems Department of Biochemistry St George's Hospital Medical School London S.W.17, U.K.
Biophysical and Physlologleal Systems Analysls Erol Basar. Pp. 428. Addison-Wesley Publishing C o m p a n y , Inc. Mass. U S A 1976. Cloth $24.50, p a p e r b a c k $12.50. This book attempts to fill an obvious gap between classical physiology and a mathematical approach to biological problems. It succeeds because the author gives background coverage of the physiological systems under review before discussing the theory of systems analysis. The reader is provided with simple diagrams illustrating the related facts, using only the minimum of mathematical trimmings. Hence it is readily acceptable to students who wish to obtain a working knowledge of the components of behaviour and are interested in their interpretation. The rules and concepts of biological processes are defined as properties relating to the input and output of a given system. Earlier chapters deal with the general principles and classification of systems analysis, giving as examples of Abstract methods the study of transient responses, frequency characteristics and oscillatory behaviour whilst the more conventional procedures of ablation and pharmacological application are cited as Special methods of analysis. Subsequent chapters offer a more detailed application of analytical theory to different biological systems. The subject of circulatory autoregulation is chosen to illustrate mechanisms that do not require continual control by the nervous system. Several hypotheses are described on the intrinsic dynamic properties of smooth muscle to elicit a common causal factor; other examples are taken to illustrate the outputs of non-linear systems in which, however, the reader is expected to have the basic mathematical knowledge applicable to model-experiments. Of particular interest to the neurophysiologist is the section dealing with electrical signals from the brain. This is a fairly comprehensive study ranging from the spontaneous rhythms of large neuronal populations to the evoked potential components arising from various input signals. The dynamics of brain potentials during sleep and the waking state are correlated with samples of structural organization and of selective blocking by drugs. The author points out the value of computational methods of analysis and some of the difficulties encountered, but limits his data processing to selective averaging of the stored recordings. There is no reference to studies of post stimulus time histograms and crosscorrelation functions. It is a pity, also, that these analytical methods have not been applied to single unit discharges. As far as the presentation is concerned, this book can be highly recommended. The concepts and objectives are clearly indicated at each stage and summarized intelligently. The reader may even be stimulated to search further into the intricate transkn'mations of signal coding that are presumably the basis of all behavioural reactions. P. P. N e w m a n
Department of Physiology University of Leeds, U.K.