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Drug metabolism from microbe to man
62
BIOCHEMICAL EDUCATION
Topics in Enzyme and Fermentation Biotechnology, Volume 1 E d i t e d by A l a n W i s e m a n . P p . 192. P u b l i s h e d by Ellis Horwood Ltd., Chichester, U.K., and distributed by John W i l e y a n d S o n s , 1977. £ 1 0 . 9 5 or $ 1 9 . 9 5 . This book raises to a marked degree the issue of what "biotechnology" is about. The term could be taken to include all technologies which derive from biological science. In this potential width lies the dilemma. Biotechnology may range from the specialist medical to the large-scale industrial and may encompass the agricultural, marine and environmental fields. The implementation of biotechnology requires rigorous application of engineering principles which is properly termed biochemical engineering. Fermentation technology is often interpreted to have quite a narrow meaning, namely aerobic or anaerobic growth of microorganisms to produce industrial products. However the same principles apply, for example, to sewage treatment, the microbial corrosion and fouling of large structures such as cooling towers. microbial leaching of ores and silage making. Enzyme technology seems at present to be used to describe any practical application in which enzymes may have a role. Since enzymes are the catalysts of all living processes this can lead to a rather complex situation. The problems of defining enzyme and fermentation technology (the bio- is really redundant) are reflected in the great varieties of style and approach of the seven contributors to the present volume. The discussion of enzyme synthesis in continuous culture which begins the book is what may be termed applied microbiology. Its objective is to improve understanding of microbial growth. It is not directly concerned with technology. Since there is a vast literature on the subject the treatment in 28 pages has had to be a very selective one. A quite different set of rules applies to the second contribution on foam separation of biological materials. Little work has been done on technique and the review is timely. There is virtually no current technology and the chapter is really concerned with biochemical engineering principles. The third contribution on aeration of mould and Streptomycete culture fluids is addressed to a major practical problem of fermentation technology. The provision of adequate oxygen to largescale growing cultures of aerobic microorganisms is always difficult. It is made much more so by virtue of the non-Newtonian behaviour of many mould culture fluids. The level of treatment in this chapter difters from others in that very basic rheology and mixing relationships are discussed. Three contributions deal with enzyme technology and illustrate the organizational dilemma mentioned earlier. One chapter gives a valuable historical and technical s u m m a r y of the development of industrial processes for glucose isomerization using microorganisms and enzymes. A second chapter titled "Enzymic alterations of penicillins and cephalosporins" does not, as suggested by the flyleaf, deal principally with the production of new penicillins. It discusses drug resistance due to lactamases, the specificity of penicillin acylases and the non-enzymic reactions of 6 amino penicillanic acid. The contributors" complaint on the lack of an effective penicillinase inhibitor for therapy seems to have been answered by recent industrial work, for example, by Beecham. The third contribution on enzymes deals with microbial cytochromes and is mostly concerned with their properties in comparison with the m a m m a l i a n enzymes. The hope is that this work may provide a basis for the use of the microbial enzymes in assessing drug safety. Again the fly-leaf comment that the book contains an account of important advances in drug metabolite production using enzymes is rather misleading. Finally a chapter on patenting developments with microorganisms and their products summarizes some of the commercial considerations of biotechnology. The readership suggested for the series by the publishers includes biochemists, engineers and analysts working in food, brewing and
July 1977
Vol. 5
No. 3
pharmaceuticals, universities and polytechnics. The reviewer found several of the chapters stimulating but future volumes may have to identify more specifically the target audience and provide a stronger linkage between contributions. Peter Dunnill Dept. of Chemical and Biochemical Engineering University College London, U.K.
Drug Metabolism from Microbe to Man Edited by D. V. Parke and R. L. Smith. Taylor & Francis L t d . , L o n d o n , 1977. P p . 460. £ 2 5 . 0 0 . This beautifully produced book is a collection of the papers read at a three-day meeting held at the University of Surrey, Guildford in April 1976 when scientists from all over the world met to honour and pay tribute to Professor R. T. Williams who was shortly to retire from the Chair of Biochemistry at St. Mary's Hospital Medical School. The word 'drug' in the title is used in its widest sense and the papers are concerned with drugs used medicinally and with the metabolism of other foreign compounds such as food additives, pesticides and environmental pollutants. The first paper describes the historical development of our knowledge of xenobiotic metabolism indicating the proliferation of the subject in the last forty years and the increasing recognition of its practical importance. Subsequent papers fall into two groups the first dealing with the mechanisms and the second with the comparative aspects of drug metabolism. The first group contains papers covering oxidation at carbon atoms and of nitrogen and adjacent carbon atoms. Other subjects described are the use of cell suspensions and cell cultures in investigations of drug metabolism and the regulation of drug metabolising enzymes. Further papers describe conjugation reactions with glucuronic acid and sugars, with sulphate and with glutathione while a paper on pharmacokinetics gives an account of the complex interactions of the factors affecting the fate of a drug in the body. The second group includes contributions on the general aspects of comparative drug metabolism; the metabolism of xenobiotics by microbes (with particular attention to the effect of the gut microfiora), plants, fish, avian species and the comparative metabolism of foreign compounds by invertebrates. Other papers describe the comparative aspects of drug metabolism in m a m m a l s with respect to pre-conjugalion and conjugation reactions. A paper on drug metabolism in the horse and its relevance to the detection of dope is an example of a particular application of the study of xenobiotic metabolism. The investigation of pattern of drug metabolism in n o n - h u m a n primates is described and the value of these animals as models for the investigation of drug metabolism in h u m a n s is uiscussed. Further papers deal with drug metabolism m man, individual variation in the h u m a n response to drugs and with pharmacogenetics and h u m a n disease. Finally. Professor Williams in a short, but stimulating, paper considers future developments emphasising the wide applications and practical importance of this fascinating subject and the enormous amount of work still to be done. The twenty-two papers contained in the book were given by experts in their particular fields: each briefly summarises early v.'ork or refers to suitable reviews and then gives an authoritative account of the latest developments with a full list of references. The book is provided with detailed indexing of authors, chemical compounds and species. It is a most valuable work of reference. with information, presented in a highly readable form, on all branches of drug metabolism including some aspects It) which attention is less frequently given. Sybil P. James Department of Biochemistry, I'he University of Birmingham, U.K.
BIOCHEMICAL EDUCATION
Topics in Enzyme and Fermentation Biotechnology, Volume 1 E d i t e d by A l a n W i s e m a n . P p . 192. P u b l i s h e d by Ellis Horwood Ltd., Chichester, U.K., and distributed by John W i l e y a n d S o n s , 1977. £ 1 0 . 9 5 or $ 1 9 . 9 5 . This book raises to a marked degree the issue of what "biotechnology" is about. The term could be taken to include all technologies which derive from biological science. In this potential width lies the dilemma. Biotechnology may range from the specialist medical to the large-scale industrial and may encompass the agricultural, marine and environmental fields. The implementation of biotechnology requires rigorous application of engineering principles which is properly termed biochemical engineering. Fermentation technology is often interpreted to have quite a narrow meaning, namely aerobic or anaerobic growth of microorganisms to produce industrial products. However the same principles apply, for example, to sewage treatment, the microbial corrosion and fouling of large structures such as cooling towers. microbial leaching of ores and silage making. Enzyme technology seems at present to be used to describe any practical application in which enzymes may have a role. Since enzymes are the catalysts of all living processes this can lead to a rather complex situation. The problems of defining enzyme and fermentation technology (the bio- is really redundant) are reflected in the great varieties of style and approach of the seven contributors to the present volume. The discussion of enzyme synthesis in continuous culture which begins the book is what may be termed applied microbiology. Its objective is to improve understanding of microbial growth. It is not directly concerned with technology. Since there is a vast literature on the subject the treatment in 28 pages has had to be a very selective one. A quite different set of rules applies to the second contribution on foam separation of biological materials. Little work has been done on technique and the review is timely. There is virtually no current technology and the chapter is really concerned with biochemical engineering principles. The third contribution on aeration of mould and Streptomycete culture fluids is addressed to a major practical problem of fermentation technology. The provision of adequate oxygen to largescale growing cultures of aerobic microorganisms is always difficult. It is made much more so by virtue of the non-Newtonian behaviour of many mould culture fluids. The level of treatment in this chapter difters from others in that very basic rheology and mixing relationships are discussed. Three contributions deal with enzyme technology and illustrate the organizational dilemma mentioned earlier. One chapter gives a valuable historical and technical s u m m a r y of the development of industrial processes for glucose isomerization using microorganisms and enzymes. A second chapter titled "Enzymic alterations of penicillins and cephalosporins" does not, as suggested by the flyleaf, deal principally with the production of new penicillins. It discusses drug resistance due to lactamases, the specificity of penicillin acylases and the non-enzymic reactions of 6 amino penicillanic acid. The contributors" complaint on the lack of an effective penicillinase inhibitor for therapy seems to have been answered by recent industrial work, for example, by Beecham. The third contribution on enzymes deals with microbial cytochromes and is mostly concerned with their properties in comparison with the m a m m a l i a n enzymes. The hope is that this work may provide a basis for the use of the microbial enzymes in assessing drug safety. Again the fly-leaf comment that the book contains an account of important advances in drug metabolite production using enzymes is rather misleading. Finally a chapter on patenting developments with microorganisms and their products summarizes some of the commercial considerations of biotechnology. The readership suggested for the series by the publishers includes biochemists, engineers and analysts working in food, brewing and
July 1977
Vol. 5
No. 3
pharmaceuticals, universities and polytechnics. The reviewer found several of the chapters stimulating but future volumes may have to identify more specifically the target audience and provide a stronger linkage between contributions. Peter Dunnill Dept. of Chemical and Biochemical Engineering University College London, U.K.
Drug Metabolism from Microbe to Man Edited by D. V. Parke and R. L. Smith. Taylor & Francis L t d . , L o n d o n , 1977. P p . 460. £ 2 5 . 0 0 . This beautifully produced book is a collection of the papers read at a three-day meeting held at the University of Surrey, Guildford in April 1976 when scientists from all over the world met to honour and pay tribute to Professor R. T. Williams who was shortly to retire from the Chair of Biochemistry at St. Mary's Hospital Medical School. The word 'drug' in the title is used in its widest sense and the papers are concerned with drugs used medicinally and with the metabolism of other foreign compounds such as food additives, pesticides and environmental pollutants. The first paper describes the historical development of our knowledge of xenobiotic metabolism indicating the proliferation of the subject in the last forty years and the increasing recognition of its practical importance. Subsequent papers fall into two groups the first dealing with the mechanisms and the second with the comparative aspects of drug metabolism. The first group contains papers covering oxidation at carbon atoms and of nitrogen and adjacent carbon atoms. Other subjects described are the use of cell suspensions and cell cultures in investigations of drug metabolism and the regulation of drug metabolising enzymes. Further papers describe conjugation reactions with glucuronic acid and sugars, with sulphate and with glutathione while a paper on pharmacokinetics gives an account of the complex interactions of the factors affecting the fate of a drug in the body. The second group includes contributions on the general aspects of comparative drug metabolism; the metabolism of xenobiotics by microbes (with particular attention to the effect of the gut microfiora), plants, fish, avian species and the comparative metabolism of foreign compounds by invertebrates. Other papers describe the comparative aspects of drug metabolism in m a m m a l s with respect to pre-conjugalion and conjugation reactions. A paper on drug metabolism in the horse and its relevance to the detection of dope is an example of a particular application of the study of xenobiotic metabolism. The investigation of pattern of drug metabolism in n o n - h u m a n primates is described and the value of these animals as models for the investigation of drug metabolism in h u m a n s is uiscussed. Further papers deal with drug metabolism m man, individual variation in the h u m a n response to drugs and with pharmacogenetics and h u m a n disease. Finally. Professor Williams in a short, but stimulating, paper considers future developments emphasising the wide applications and practical importance of this fascinating subject and the enormous amount of work still to be done. The twenty-two papers contained in the book were given by experts in their particular fields: each briefly summarises early v.'ork or refers to suitable reviews and then gives an authoritative account of the latest developments with a full list of references. The book is provided with detailed indexing of authors, chemical compounds and species. It is a most valuable work of reference. with information, presented in a highly readable form, on all branches of drug metabolism including some aspects It) which attention is less frequently given. Sybil P. James Department of Biochemistry, I'he University of Birmingham, U.K.