T I B S - March 1984 118 oxidized unless they underwent a preliminary activation and that this activation was dependent on ATP8,13.14,suggested that ...

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T I B S - March 1984

118 oxidized unless they underwent a preliminary activation and that this activation was dependent on ATP8,13.14,suggested that the intermediates formed during fatty acid oxidation were not the free acids. The work on the CoA-dependent acetyltransfer reactions had indicated that the actual acetyl donor might be an acetylated form of CoA. This was conclusively established by the brilliant work of Lynen and his colleagues 11,12.These workers isolated and partially purified acetyl-CoA from baker's yeast which had been actively oxidizing ethanol and glucose. The biological assay of acetyl-CoA was based on its capacity to replace the CoA-dependent acetate--ATP donor system needed to acetylate sulphanilamide in a pigeon liver preparation. Lynch and his colleaguesn identified acetyl-CoA as an acetyl-mercaptide of the type R.S.CO.CH3. Mitchondria of animal tissues seem to be well equipped with all the enzymes needed for both fatty acid oxidations and the operation of the citric acid cycle14,15. Indeed, a saline extract of an acetone powder of mitochondria may yield all the enzymes of the fatty acid oxidation system. These enzymes are described in detail in most

modem text books of biochemistry and of a new trend in our thinking of the course need no description here. Not only the fatty of oxidative metabolism of the fatty acids. acids, but aromatic acids (e.g. benzoic) can form CoA derivatives prior to further reac- References 1 Dakin, H. D. (1922) Oxidation and Reductions tions and these may form competing in the Animal Body Longmans, Green & Co. analogs to the acyl-CoA complexes. Even 2 Quastel, J. H. and Wheatley, A. H. M. (1933) the selective herbicide, 2;4 dichlorphenoxyBiochem. J. 27, 1753 acetic acid, may be derived by bacterial 3 Jowett, M. and Quastel, J. H. (1935)Biochem. J. oxidation from the longer chain 29, 2143; 2159 and 2181 dichlorphenoxyacyl-acids. D-biotin may be 4 Edson, N. L. (1935)Biochem. J. 29, 2082 5 McKay, E. M., Wick, A. N. and Barnum, C. P. degraded oxidatively by kidney cortex, los(1940)J. Biol. Chem. 136, 503 ing growth promoting activity and at the 6 Breusch, F. L. (1948)Advances in Enzymology same time its terminal acyl-carbon atoms 8, 243 which appear to enter the citric acid cycle. 7 Weinhouse, S., Medes, G. and Floyd, N. F. But whether the vitamin forms a CoA com(1944)£ BioL Chem. 155, 143 8 Lehninger, A. L. (1945)J. Biol. Chem. 161,413; plex in addition to its well known other 437; (1946)ibid 164,291 complexes is still a matter for investigation. There are many, I know, who consider 9 Lipmann, F. and Kaplan, N. O. (1946) J. Biol. Chem. 162, 743 that the modem view of the mode of fatty 10 Novelli, G. D. and Lipmann, F. (1950)J. Biol. acid oxidation in the animal body dates Chem. 182, 213 from the time of the use of cell free suspen- 11 Lynen, F., Reichert, E. and Rueff, L. (1951) Ann. sions and labelled isotopes. But I feel that it Chem. 574, 1 commenced in 1933 with the first use of 12 Lynen, F. and Ochoa, S. (1953) Biochim. Biophys. Acta 12, 299 liver slices for the study of hepatic oxida13 Munoz, J. M. and Leloir, L. F. (1943) J. Biol. tion, using methods for accurate measureChem. 147, 355 (1944)lb/d 153, 53 ments and varied experimentation, in a 14 Grafflin, A, L. and Green, D. E. (1948)J. BioL small laboratory in a mental hospital in Chem. 176, 95 Whitchurch near Cardiff, Wales. It was 15 Lehninger, A. L. and Kennedy, E. P. (1949) J. Biol. Chem. 179,957 surely this that marked the commencement

Book Reviews Below-standard


by J. David Rawn, Harper and Row, 1983. £13.00 (xxxi + 1 139pages) ISBN 0 060 45335 4 The size (over I 100 pages) of this latest addition to the ranks of biochemistry textbooks bears witness to the continued expansion of the subject. Inevitably one has to compare this volume with its well-established predecessors, in particularly the popular books by Stryer and by Lehninger. The organization of the material here is conventional. The first part deals with the conformation and function of biological macromolecules; as well as describing the structures of the various classes of macromolecules, it contains chapters on enzyme catalysis and kinetics, on purification methods and on membrane structure. The second part surveys metabolic pathways including chapters on oxidative phosphorylation and photosynthesis. The final section, entitled 'molecular biology' covers DNA replication, transcription and translation, and regulation of gene expression.

gluconeogenesis and a 1973 review of protein kinases will be of great value to The illustrations which complement the student in view of the rapid progress the text are in black, grey and two in these areas. Secondly, there are problems given at shades of pink. The diagrams are clear and generally well-designed. A novel the end of each chapter, but the answers feature is the liberal use of three- are not provided. Apparently these are dimensional illustrations and a viewer is available in a companion volume but provided for visualizing them in 3-D. this arrangement may not appeal to The viewer, a rather flimsy contraption hard-up students. Thirdly, I have serious reservations in cardboard, worked quite well for me although I found I soon tired of using it. about the choice of subject matter. In There is no doubt that the text conveys particular the whole area of regulation is of lot of information and there is much given scanty coverage. Insulin, for that is worthy about this volume. How- example, is dealt with in one sentence. ever, there are many aspects that are Metabolic regulation is not covered open to criticism. Firstly, the purpose of adequately: for example, the discussion the references that conclude each chapter of glycogen metabolism is very incomdoes not seem to have been thought plete, omitting any mention of phosout; they are not classified in any way, phorylation of glycogen synthetase by comparing particularly unfavourably in kinases other than cyclic AMP-depenthis respect with the arrangement in dent protein kinase. Regulation of Stryer; they are listed without comment pyruvate dehydrogenase phosphorylation and are often too general to be helpful. fares little better. Secretion and the I question, for instance, the value of signal hypothesis are not mentioned. giving as further reading for the chapter The biochemistry of muscle contraction on enzyme catalysis a reference to all 13 is not covered. Membrane transport is volumes of The Enzymes. In many cases dealt with only sketchily and hormone they are out of date; it is difficult to receptors not at all. In fact, treatment of imagine, for example, in Chapter 17 the whole topic of hormonal action is that a 1971 review of regulation of unsatisfactory and often erroneous. biochemistry

TIBS - March 1984


Thus steroid hormones are stated to act solely via protein phosphorylation and the effects of et-adrenergic agents are said to be exerted solely via cyclic GMP. Molecular biology also has many omissions: only the 13-form of DNA is described; the role of cro and repressor

in bacteriophage h is not discussed; transposons are not mentioned. It is hard therefore to envisage a biochemistry course for which this would be an adequate basic text. Neither the presentation nor the content quite match the high standard of existing

The logic of molecular evolution Molecular T h e o r y of Evolution O u t l i n e of a Physico-Chemical T h e o r y of the Origin of Life

comprehensive biochemistry textbooks. S. J. H. ASHCROFT

Nuffield Department of Clinical Biochemistry', University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.

with copolyamino acids, does not alter Darwin's principle of selection internally. Rather it provides in advance of the process of selection a dynamic alternative of variation as the substrate upon which natural selection then operates. This book will be of interest to those who are interested in mathematical models, especially for molecular or organismic evolution. It has the special virtue of a lucid organization and presentation of the hypercycle concepts of Eigen and Schuster. However, Kiippers does not draw or recognize a distinction between the approaches of backward extrapolation of modern events and forward retracement of early evolutionary events. In the context of forward evolution, careful reading of appropriate papers that he cites could acquaint one with the fact that a number of the questions that he raises were answered years ago.

those conditions opportunity for steric effects of monomer sidechains to be expressed is maximal due to undiluted by Bernd-Olaf [email protected], Springer Verlag, proximity of the sidechains. Other ways in which the results of 1983. DM 79.00/$31.60 (ix + 321 pages) experiments on self-organized systems ISBN 3 540 12080 7 ab initio disagree with Kiappers' assump"['his monograph is a scholarly review of tions are several (cf. KiJppers' own various mathematical models of the re- reference on p. 280 and the bibliography action kinetics of replicating molecules. of Fox, TIBS, Aug. 1983, pp. 277-278). The chapters deal successively with the We point out especially, however, that molecular basis of biological information, the information of protocells was not 'an principles of molecular selection and inevitable last stage in the process of evolution, the transition from the non- molecular self-organization' (p, 242). living to the living, and model and reality The experiments indicate that stage to (the logic of the origin of life). The book have been an event immediately subseincludes mathematical appendices. quent to formation of non-random therThe mathematical richness of Eigen's mal proteins, with the now demonstrated catalytic hypercycle is well documented. thermal protein-catalysed polymerization However, mathematical modeling of of nucleotides to have come later on the the origin and evolution of life is not primitive Earth. Without the conceptual automatically physical reality. In fact, in artifacts of 'self-replicating molecules', the concluding paragraph (p. 283), which are not in accord with reality, SIDNEY W. FOX KiJppers presents his view of the present Kfippers' mathematical scheme appears Institute for Molecular and Cellular Evolution, status of the problem by stating: 'We to us to be fruitless. This unsupported University of Miami, Coral Gables, FL 33134, are rather confronted with an information assumption also distorts Darwinian USA. problem whose solution calls for a new evolution. KOICI-tl RO MATSUNO physical concept of natural self-organiNon-randomness of the matrix for Department of Systems Science, Technological zation involving a physical formulation organic evolution, as now demonstrated Universi~ of Nagaoka, Nagaoka 949-54, Japan. of Darwin's principle of natural selection', If the author would step outside of the limits that he sets for himself, he Inorganic biochemistry comes of age would be in a position to recognize that one such concept has been available, Inorganic Biochemistry (Nobel that biochemistry is not organic chemistry On p. 280, Kiippers indirectly mentions Symposium 56) but is a chemistry related in part to the that principle of the spontaneous generchemistry of minerals and compounds of edited by Ragnar Osterberg, ation of non-random sequences in the many elements. The inorganic comchemical condensation of amino acids, Royal Swedish Academy of Sciences, pounds provide the best catalytic centres 1983. SwKr 300 (164 pages) ISSN 0004 but he dismisses the results as 'slight of living systems, the best purely structural 2056 selectivity' although 'many such random units, and many sensing devices. There proteins were found to possess some The joys of science are often in the is no longer any doubt that many in(admittedly low) catalytic activity (cf, surprises. The biggest surprise however organic elements are essential. Even the Fox, 1973)'. For his examples of 'slight is to see a subject with an apparently organic chemist has been forced to make selectivity' he cites two papers describing nonsensical title become accepted. In chiral phosphate! Already a symposium condensation of amino acids in solvents, 1948 I started looking at the methods of such as this on the topic of inorganic To our best knowledge, polymers pre- analysis for zinc with an eye on biologi- biochemistry can be looked at as a pared in neither solvent: polyphosphoric cal systems. To have written in my signpost to what has been and we can acid nor water, have been reported as thesis 'At about this date (1948) inorganic ask what will be. Most of the papers in having catalytic activity. The various biochemistry began to evolve' would the volume are about the molecular catalytic activities reported for thermal have been treated by every biochemist structures of required metal complexes proteins by numerous laboratories have and chemist of my acquaintance with usually locked in proteins. This covers however been found in highly non- scorn. What could 'inorganic biochemis- much of the present biochemistry of random copolyamino acids made in try' mean? Yet this is the title of Nobel copper, zinc, iron, molybdenum, manmolten amino acid mixtures. Under Symposium No. 56. It has turned out ganese and some of that of magnesium