Textbook of biochemistry with clinical correlations

Textbook of biochemistry with clinical correlations

TIBS 1 8 - FEBRUARY 1993 Intermediate Metabolism of Carbohydrates', Johnson provided a schematic diagram of the cycle, described its essential compon...

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TIBS 1 8 - FEBRUARY 1993

Intermediate Metabolism of Carbohydrates', Johnson provided a schematic diagram of the cycle, described its essential components in detail and drew several important conclusions. He suggested that (1) the citric acid cycle provides a mechanism for the oxidation of carbohydrate in animal tissues, (2) pyruvic acid can also be removed both by an aerobic dismutation, and by condensation leading to the formation of ketone bodies and (3) fumaric acid is a stage in the oxidative cycle, but can also be removed by anaerobic reduction to succinic acid. When the work was finally completed, a brief account of the citric acid cycle work was offered to Nature, but was rejected due to lack of space. Krebs responded by offering the famous full paper to Enzymologia, with Johnson as the co-author. No obvious excitement was shown by Krebs or any other member of the laboratory when the cycle was eventually formulated. Johnson himself was happy merely to have successfully concluded his PhD studies, and was surprised when he later heard that Krebs had received a Nobel Prize for the work.

Johnson then left Sheffield to work for British Drug Houses (BDH). On the first day, he recalled how the research director told the foreman to forget the 'Dr' in front of his name and set him to work on insulin production, which involved feeding large amounts of pancreas into a mincer. Fortunately, more challenging opportunities eventually came his way, leading to promotion to assistant works manager. After World War II he moved to Liverpool, where he became a manager of a small chemical plant, which was later taken over by Commonwealth Zinc (later Rio Tinto Zinc). Here Johnson made rapid progress and eventually became a member of its UK board. He has now retired and lives in London. After a period of some 50 years, when Johnson and Krebs never saw nor corresponded with one another, they again met at a celebration in honour of Krebs given in Dallas in 1980. Johnson was asked to recall his memories of his research student days, and he concluded his remarks in the following words: 'People often ask "What has biochemistry done for me?" My reply would be that it gave me, at an early and ira-

pressionable age, the opportunity of working with one of the world's finest minds, to see the speed at which he reached conclusions, to try - and I say this advisedly - to tr:,' and understand his thought processc~ and it gave me a yardstick to measure in other people that I have met in later years. Throughout my years I have occasionally been asked (and it happened about six months ago) "Didn't you once work with Krebs?" and i smile a superior smile and say, "Yes, I did." That was what biochemistry did for me, and for that, Sir Hans, I thank you.'

Acknowledgement This article is based on information kindly provided by Dr Johnson in a recent interview w i t h the author.

References I Krebs, H. A. (1964) NobelLectures(19421962), pp. 399-410, Nobel Foundation, Elsevier 2 Krebs, H. A. and Johnson, W. A. (1937) Biochem.J. 31, 645-660 3 Krebs, H. A. and Johnson, W. A. (1937) Biochem.J. 31, 772-779 4 Krebs, H. A. and Johnson, W. A. (1937) Enzymologia4, 148-156 5 Krebs, H. A., Salvin, E. and Johnson, W. A. (1938) Biochern.J. 32, 113-117

B00KREVIEWS What to recommendto a medical student? Textbook of Biochemistry with Clinical Correlations edited by T. M, Devlin, Wiley-Liss, 1992, £55,95 (xxiii + 1185 pages) ISBN 04 71 51348 2

This multi-authored textbook provides much essential information on basic biochemistry. It has a traditional list of contents, beginning with a discussion of the major structural components of cells. This includes cell structure, proteins, enzymes, membranes and their roles. Then comes a section on metabolism followed by one on information transfer and its control. Signal transduction and amplification merits three chapters while some of the more physiological chemical aspects, such as gas transport and pH regulation or the principles of nutrition, are covered in the final six chapters. The


chapters (28 in all) are broadly of equal length and, although written by different authors, are rather similar in writing style. I found the text easy enough to understand although a little lacking in panache at times. The excellence of the early Lehninger is difficult to emulate in that regard. Overall the book aims to do three things. First, to present a clear background to the biochemistry of mammalian cells. Second, to place biochemical reactions in the context of cellular events and then as part of physiological processes in whole animals. Third, it gives specific examples of human diseases where the underlying biochemistry is understood and accounts for the clinical conditit,,. There is sufficient detail in most areas for the book to serve as a basic text during the pre-clinical years of a medical course although some parts (such as immunology) may be found too superficial. Each chapter is divided into many small sections which often contain snappy and informative titles to subsections. There are many diagrams

(for which the margins are frequently used) such that almost 40% of the printed area is taken up by figures. These diagrams are of high quality and usually clear and accurate. However, the limited use of colour (basically only shades of red) creates a poor impression compared to the very fine illustrations of Stryer or Matthews and Van Holde, for example. The general layout and style of presentation also look a little old-fashioned compared with other current textbook rivals. The clinical correlates shown in the text are, of course, limited by those diseases known and where a biochemical explanation is forthcoming. Thus, there are large sections of text without a specific clinical correlation. In one or two cases an example is given without a specific disease in mind, for example, in the use of liposomes as drug carriers. The clinical correlates were usually interesting and cited specific references which were generally about three or four years old. It may be nice to expand the number and size of the clinical examples in the future, since I am sure that medical

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students will find the information therein much more stimulating than, say, metabolic pathway details. The size of the individual sections on clinical correlates could do with some balancing. For example, Lesch-Nyham Syndrome receives nearly a page of discussion, whereas atherosclerosis is dismissed in about 200 words. Considering the relative importance of these complaints ! would have thought that the length of the two sections could have been reversed. Some diseases, such as HIV infection, were also dealt with in surprising brevity. However, having made these points, the inclusion of clinical correlations in the book is a strong point and obviously welcome for medical students. Indeed, some of these sections (particularly in the nutritional chapters) make for very entertaining reading. At the end of the book is a section entitled 'Review of Organic Chemistry'.

This covers mainly definitions and some basic structures of carbohydrates, lipids and so on. it didn't seem to add much to the worth of the book and ! felt that the information could have been better (and often was) included with the relevant section of text. The index stood up adequately to a few trials. At the end of each chapter are a set of questions and answers mainly in a multichoice format. These are quite useful although ! would have preferred (or wanted in addition) a good summary of the really essential points of each chapter. A bibliography to review articles on the biochemistry in each chapter is also given and again these provide reasonably up-to-date material for the keen student to find further reading. In summary, Devlin's book provides a good sound background for the biochemical aspects of a medical student's course. The presence of clinical

Electroenzymesby the master

important and interrelated functions: to consolidate descriptL,~e information proving the existence of the class of enzymes; to formulate the behavior of individual enzymes within the class in precise kinetic and thermodynamic terms; to introduce the still embryonic subject of molecular mechanisms for several of the enzymes; and, with exceptional didactic style, to make the whole information accessible to a very broad audience. Of the half-dozen families of electroenzyme that have been studied with reasonable care so far, four are considered in this monograph. The smallest molecules, having probably the simplest mechanism, are semlcrystalline rhodopsin-like molecules found in purple membrane patches oi certain brine-loving bacteria, such as Halobacterium halobium. In these organisms, which normally also live at very high light intensities, the bacterial rhodopsin transduces a small fraction of energy from captured photons into a current of protons. Professor L~uger has provided a compact review of this enzyme (chapter 6), describing the temporal kinetics of the photon-induced current, outlining the lmown structure of the molecule, and discussing the probable origin of the proton current from a PKa shift in the retinale chromophore. More complex (and generally less well understood) reactions, by which electron flow drives proton currents are discussed (chapter 11) for mitochondrial cytochrome oxidase, which is one in a diverse family of redoxcoupled electroenzymes. A short unit

ElectrogenicIon Pumps by Peter L~uger, SinauerAssoc. Inc., 1991. £34.95 (iii +313 pages) ISBN 0 87893 451 0 Great artists differ from other mortals in having overwhelming technique at Instant command, so they can completely devote Intellect to the aesthetics a.~d communication which become their art. So It was with ProfessL~r L~iuger, who has made a monograph on biophysics into an aesthetic experience. Biological membranes contain a special class of enzymes that catalyse fuel-cell reactions, converting the energy of hydration--dehydration transitions or of oxidation-reduction transitions directly to (or from) electric energy, by separating (or recombining) ionic charges across the membranes. The existence of such molecular generators, which have generally been called 'electrogenic ion pumps' but were more economically dubbed 'electroenzymes' by J. B. Chapman, was postulated about 50 years ago and has generally been accepted for about 20 years. Detailed molecular understanding, however, is now only beginning to emerge. This book, Electrogenic Ion Pumps, appearing in timely fashion, and from the hand of this very special author, serves several

correlations sets it apart from other textbooks which may be stronger in their discussion of basic biochemistry. In future editions it is hoped that some effort may be given to improving the general layout and in the presentation of figures. I found refreshingly few errors (and these were usually minor) in those areas ! was competent to assess and I thought that the references for further reading were as up-to-date as one could expect. The quality of modern biochemistry texts is now very high but Devlin's book should be able to compete well for a significant share of the preclinical student market.

J. L. HARWOOD Department of Biochemistry, University College, PO Box 78, Cardiff, UK CF11XL.

(chapter 10) is also devoted to central observations and probable reaction schemes of large oligomeric proteins, the FoFrATPases (or now, just 'F-ATPases') present in and on photosynthetic, respiratory and bacterial membranes for the main purpose of energy conservation: i.e., converting proton currents from the above devices into that general currency of bioenergetics, ATP. L~iuger's most detailed and informative discussion, however, is devoted to a large family of electroenzymes, the P-ATPases, inhabiting the plasma membranes of all eukaryotic cells (and some bacteria) for the purpose of driving ion flow in the interests of osmoregulation, pH regulation, secretion and, indirectly, of carbon/substrate accumulation. These enzymes, which closely resemble each other in secondary and tertiary structure, despite considerable evolutionary divergence in primary structure, drive ion currents from the energy of ATP hydrolysis via a cycle of protein phosphorylation and dephosphorylation. Different species in the family use as many as five different ionic currencies: protons (hydronium ions), sodium ions, calcium ions, potassium and perhaps chloride. Prototype enzymes in the family are the Na',K'-ATPase of animal plasma membranes (chapter 8), the Ca2*-ATPase of sarcoplasmic reticulum (chapter 9), and the H'-ATPase of fungal membranes (chapter 7). These enzymes, which have the longest history in transport measurements per se, offer a rich comparative basis for the exposition of reaction mechanisms. The book provides