- Email: [email protected]
The life that lives on man
TIBS - February 1977
46 material. This author has compared, with scrupulous exactitude, nearly all procedures hitherto published in the literature and offers a series of very valuable conclusions and advice on which method should be used for which specific question in the subsequent analysis of the nuclear membrane fractions. The introductory chapter by E.A. Smuckler, M. Koplitz and D. E. Smuckler gives a brief summary of nuclear morphology and presents the various principles in methods of isolating animal nuclei (plant material is indeed largely underrepresented). However, this article in particular, but to some degree the whole book, suffers from the unsatisfactory print quality of the electron micrographs. Apart from this deficiency, the book is such a valuable compilation and critical guide that one can hardly imagine a biologist or biochemist working with nuclei who can afford not to have it. WERNER W. FRANKE W. W. Franke is head of the Division qf Membrane Biology and Biochemistry at the Institute of Experimental Pathology, German Cancer Research Center, Heidelberg, G. F. R.
Flavins and Flavoproteins edited by T. P. Singer, published by Elsevier, Amsterdam, 1976. Djl.258.($99.50) (xiii+813pages)
In the spring of 1975 the Fifth International Symposium on Flavins and Flavoproteins was held in San Francisco. The original meaning of a symposium was an Ancient Greek drinking party, and although in this instance there were no oldAthenian participants, the editor makes it clear in his introduction that a very good time was had by all. In fact, like many ‘international’ meetings, the majority of contributions came from the U.S.A., but with respectable offerings from Europe and Japan. During four days, 92 original papers were presented and these, apart from three too late for inclusion, have each a ‘chapter’ in this large volume, grouped conveniently into thirteen parts. The editor and host, T.P. Singer, provides a useful introduction, incidentally revealing the familiar but often unadmitted truth that enthusiasm for a chosen research area derives as much from aesthetic satisfaction as fr,jrn the conventional scientific motivations.
Now for the papers. We start in at the deep end with oxygen activation, papers which are hard going except for specialists, but with excellent presentations and discussions. The following ‘Bacterial Luciferase’ papers are more congenial, directed mainly at elucidating the reaction intermediates, and all agree that FMN is not itself the bioluminescent emitter. Good summaries make rapid comprehension easier and here, and throughout the book, one is impressed by the capability and skilful use of the many physical techniques employed. Interest is evenly divided between the macromolecular properties and reaction pathways of oxygenases (mostly hydroxylases) in the following eight papers, impressive in the wide variety of reactions catalysed by these enzymes. Next, we explore proton abstraction processes in several well-defined, enzyme-substrate systems, mostly down-to-earth stuff, except for one paper devoted to bio-organit’ mechanisms, and another on chargetransfer complexes. Covalently-bound ‘old’ and ‘new’ flavins are investigated in a larger group of papers, followed by an intriguing selection of studies using flavin analogues in which N is replaced by C or S. The later papers in this section have formidable but informativeltreatmentsof the intimate electronic structure of the flavin nucleus. The molecular structure and binding properties, redox mechanisms and molecular evolution of flavodoxins comprise the following section. That old favourite, lipoyl dehydrogenase, has a central position in this book, as it has in the hearts of the older flavinophiles. Active site properties and reaction mechanisms are of prime interest here, and obviously this old friend still has much to reveal. We then come to complex metallo-flavoproteins, in papers much more of the ‘enzyme isolation and characterization’ type previously rare in this8volume.Adrenodoxinsand flavoprotein oxidases have each a small group of contributions, and, nearing the end of the book, we swing away from the biophysical and mechanistic approach hitherto dominant, and conclude with riboflavin biosynthesis and metabolism; and a more heterogeneous group of unclubbable ‘special topics’. Taken altogether, the standard of the papers is remarkably high with many impressive examples of the power of the newer biophysical, especially spectroscopic, techniques in the flavin field. In many cases they would serve as excellent models for research workers who are unfamiliar with these experimental approaches. Although it is regrettable that summaries are not always provided, the discussions are almost always stimulating and
should reassure those who may doubt that we have much more to learn about flavoproteins that innumerable questions remain as yet unanswered. The text is well illustrated and remarkably free from printing errors (I counted about twenty in the whole book), and the index is reasonably helpful. As with all such collections, some of the material has been published elsewhere, but appearing as it does relatively soon after the symposium, this is not a serious shortcoming. Despite the formidable cost of this book, the quality and breadth of the material gathered together in this collection make it an essential acquisition by any biochemical or biophysical laboratory actively engaged or interested in the flavin field. F. W. J. TEALE F. W. J. Teale is the Reader in Physical Biochemistry at the University #Birmingham, Edgbaston. U.K.
Skin deep The Life That Lives on Man by Michael L. A. Andrews, published by Faber & Faber, London, 1976. &4.95 (approx. $9.-) (183 pages)
There are moderate-sized tree trunks every thirty meters. They arise from greasy pits. Scattered over the surface are irregular salt-encrusted rims of drain-pipes disgorging droplets of water several meters across at the slightest rise in temperature. The inhabitants of this savanna are square in appearance and about the size of a shrew. They stretch and make a crackling sound and break into two individuals every half an hour or so. If you could look at your skin at an enlargement of 10000 times, this is how you would see your hairs, your openings of sweat glands and your bacteria. The healthy human skin is an ecosystem, just like a pond or a wood. In an environment of keratin soil with hairs and sweatgland discharge, a dense bacterial flora not only breaks down different components (causing, among other things, nasty smells) but also protects us against pathogenic species. On less healthy skins, we could find fleas, head- or crab lice drinking their blood meals, and sometimes even an itch mite taking great pains in burrowing just under the keratin layer. Other arthropods are found on healthy skins but are vectors of pathogenic organisms. On less populated or damaged skin the bacterium Staphylococcus aureus causes much destruction. Sometimes warts arise as a host action governed by a Papova virus. Much more happens on our skin, healthy or sick, and Andrews tells us about
TIBS
- February
47
1977
Top, dust mites (Dermatophagoides pteronissimq on human skin; under, closeup of front legs and jaws.
it in 183 very readable pages. It must be said that he has carefully digested the scientific reports of the different disciplines that study the skin. His book should be read by anyone interested in his very own microscopic pets ! J. VAN BRONSWIJK
J. van Bronswijk works in the Dermatology Depariment at the Academic Hospital in Utrecht. The Netherlands.
.Phenomenological overkill The Enzymes of Biological Membranes: Vol. 2, The Biosynthesis of Cell Components edited by Anthony Martonosi, published by Plenum Press, New York/London, 1976. $54.- (approx. &30.-) (xvii+651 pages)
The magnitude of this book, seventeen chapters in over 600 pages with almost 3000 citations, attests to the rapidly growing interest in research on membranes and membrane-bound enzymes. In spite of our developing understanding of the nature and properties of integral membrane proteins, however, work with enzymes of this class remains an art. Few such enzymes have been purified to homogeneity, and even assaying most of them in situ in the membrane is difficult. Finding the proper conditions for assay and isolation, often involving the judicious choice of detergent
or organic solvent, is still a matter of trial and error. The chapters of this book are, in effect, progress reports of many trials and errors with many different enzyme systems, from which one can retrieve specific information on specific enzymatic reactions. As such, the book will serve a useful function for research workers in fields closely related to the topics covered. The duration of usefulness will depend upon the speed of advances in each topic area, and at the pace of current research some of these articles may be outdated very soon. The book will not be useful to those hoping to gain new general insights into the problems ofmembrane structure and function, for no attempt was made to compare or contrast common features from different chapters. It is a pity that the dissemination of important and timely review articles such as those found in this book was not accomplished at a price more cornmensurate with their useful lifetime. Some of the chapters of the book cover topics with a very limited scope, where it was felt that suflicient information was available about a specific enzyme to warrant in-depth coverage. The article by Gennis and Strominger on the ‘C,,-Isoprenoid Alcohol Phosphokinase’ and that by Gennis and Hager on ‘Pyruvate Oxidase’ represent two enzymes which have been extensively purified. The first is obviously an integral membrane protein, requiring butanol for solubility and purilication, while the second is a water-soluble protein that is activated by association with lipid. Both are probable prototypes of other membrane enzymes and warrant inclusion in such a treatise, yet each chapter summarizes data primarily from only three research articles, and one could read the original almost as easily as the reviews. A chapter on ‘Glucose-6-phosphatase’ by Nordlie and Jorgenson, and a chapter on ‘Carnitine Palmitoyltransferase and Transport of Fatty Acids’ by Hoppel, cover adequately the rather extensive work on these enzymes, including effects of hormones and drugs on enzymatic activity. In both cases the enzymes are less well characterized. There is evidence that different forms may exist which may be related to orientation with respect to the membrane. A chapter by Brady and Fishman ‘Alterations of Galactosaminyland Galactosyltransferases in Cultured Mammalian Cells and in vivo’ outlines evidence for the loss of specific enzymes involved in ganglioside synthesis in the case of virus transformation in cultured cells on the one hand, and of a metabolic abnormality found in a 3+ month old infant on the other. The effect of detergents, lipid alteration by phospholipases, and temperature
on the kinetics of UDP-glucuronyltransferase are discussed extensively by Zakim and Vessey. This activity has not been purified sufficiently to establish that it is a single enzyme, and so the mechanistic conelusions drawn from kinetic data are unwarranted even though the data are interesting. At the other extreme of scope are two extensive review articles, one by Lands and Crawford on ‘Enzymes of Membrane Phosphlipid Metabolism in Animals’ and the other by Hussey and Baddiley on ‘Biosynthesis of Bacterial Cell Walls’. These chapters account for about 30”,, of the pages and citations of the entire book. The first is organized according to the type of bonds being formed or cleaved in phospholipid metabolism, while the latter considers both the structure and biosynthetic pathways for peptidoglycan, lipopolysaccharide, and teichoic acid. While both articles cover material that has been reviewed in one form or another previously, the broad scope and orientation of these articles, showing particular attention to membrane involvement where possible, do provide a valuable reference for those seeking information on these topics. The remaining articles cover an interesting variety of topics of intermediate scope. In most cases the emphasis is on biosynthetic pathways, with specific enzymes discussed where appropriate. Topics include mammalian ether-linked glycerolipids, glycoprotein biosynthesis, mammalian and plant sterol biosynthesis, plant fatty acid synthesis and metabolism, function of membrane-bound ribosomes in eukaryotic cells, and platelet membrane enzymes involved in hemostasis. A rather speculative article reviews evidence that bacteriophage T, infection of Escherichia coli involves several intermediates and processes that are associated with the bacterial cell envelope. In discussing the relationship between ‘latency’ of giucose-6-phosphatase and related activities to the morphology of the Nordlie and Jorgenson membrane, comment that ‘experimentation in this area presently appears stalled at the phenomenological stage’. One gets the impression that most work on membranebound enzymes is also still in the phenomenological stage, though hopefully not stalled there. Perhaps this collection of review articles will stir even greater activity in the search for general principles that will contribute to a better understanding of membrane structure and function. ROBLEY
LIGHT
Robley Light is Professor and Associate Chairman oJ the Department of Chemistry, Florida State University. Tallahassee, Florida, U.S.A.
46 material. This author has compared, with scrupulous exactitude, nearly all procedures hitherto published in the literature and offers a series of very valuable conclusions and advice on which method should be used for which specific question in the subsequent analysis of the nuclear membrane fractions. The introductory chapter by E.A. Smuckler, M. Koplitz and D. E. Smuckler gives a brief summary of nuclear morphology and presents the various principles in methods of isolating animal nuclei (plant material is indeed largely underrepresented). However, this article in particular, but to some degree the whole book, suffers from the unsatisfactory print quality of the electron micrographs. Apart from this deficiency, the book is such a valuable compilation and critical guide that one can hardly imagine a biologist or biochemist working with nuclei who can afford not to have it. WERNER W. FRANKE W. W. Franke is head of the Division qf Membrane Biology and Biochemistry at the Institute of Experimental Pathology, German Cancer Research Center, Heidelberg, G. F. R.
Flavins and Flavoproteins edited by T. P. Singer, published by Elsevier, Amsterdam, 1976. Djl.258.($99.50) (xiii+813pages)
In the spring of 1975 the Fifth International Symposium on Flavins and Flavoproteins was held in San Francisco. The original meaning of a symposium was an Ancient Greek drinking party, and although in this instance there were no oldAthenian participants, the editor makes it clear in his introduction that a very good time was had by all. In fact, like many ‘international’ meetings, the majority of contributions came from the U.S.A., but with respectable offerings from Europe and Japan. During four days, 92 original papers were presented and these, apart from three too late for inclusion, have each a ‘chapter’ in this large volume, grouped conveniently into thirteen parts. The editor and host, T.P. Singer, provides a useful introduction, incidentally revealing the familiar but often unadmitted truth that enthusiasm for a chosen research area derives as much from aesthetic satisfaction as fr,jrn the conventional scientific motivations.
Now for the papers. We start in at the deep end with oxygen activation, papers which are hard going except for specialists, but with excellent presentations and discussions. The following ‘Bacterial Luciferase’ papers are more congenial, directed mainly at elucidating the reaction intermediates, and all agree that FMN is not itself the bioluminescent emitter. Good summaries make rapid comprehension easier and here, and throughout the book, one is impressed by the capability and skilful use of the many physical techniques employed. Interest is evenly divided between the macromolecular properties and reaction pathways of oxygenases (mostly hydroxylases) in the following eight papers, impressive in the wide variety of reactions catalysed by these enzymes. Next, we explore proton abstraction processes in several well-defined, enzyme-substrate systems, mostly down-to-earth stuff, except for one paper devoted to bio-organit’ mechanisms, and another on chargetransfer complexes. Covalently-bound ‘old’ and ‘new’ flavins are investigated in a larger group of papers, followed by an intriguing selection of studies using flavin analogues in which N is replaced by C or S. The later papers in this section have formidable but informativeltreatmentsof the intimate electronic structure of the flavin nucleus. The molecular structure and binding properties, redox mechanisms and molecular evolution of flavodoxins comprise the following section. That old favourite, lipoyl dehydrogenase, has a central position in this book, as it has in the hearts of the older flavinophiles. Active site properties and reaction mechanisms are of prime interest here, and obviously this old friend still has much to reveal. We then come to complex metallo-flavoproteins, in papers much more of the ‘enzyme isolation and characterization’ type previously rare in this8volume.Adrenodoxinsand flavoprotein oxidases have each a small group of contributions, and, nearing the end of the book, we swing away from the biophysical and mechanistic approach hitherto dominant, and conclude with riboflavin biosynthesis and metabolism; and a more heterogeneous group of unclubbable ‘special topics’. Taken altogether, the standard of the papers is remarkably high with many impressive examples of the power of the newer biophysical, especially spectroscopic, techniques in the flavin field. In many cases they would serve as excellent models for research workers who are unfamiliar with these experimental approaches. Although it is regrettable that summaries are not always provided, the discussions are almost always stimulating and
should reassure those who may doubt that we have much more to learn about flavoproteins that innumerable questions remain as yet unanswered. The text is well illustrated and remarkably free from printing errors (I counted about twenty in the whole book), and the index is reasonably helpful. As with all such collections, some of the material has been published elsewhere, but appearing as it does relatively soon after the symposium, this is not a serious shortcoming. Despite the formidable cost of this book, the quality and breadth of the material gathered together in this collection make it an essential acquisition by any biochemical or biophysical laboratory actively engaged or interested in the flavin field. F. W. J. TEALE F. W. J. Teale is the Reader in Physical Biochemistry at the University #Birmingham, Edgbaston. U.K.
Skin deep The Life That Lives on Man by Michael L. A. Andrews, published by Faber & Faber, London, 1976. &4.95 (approx. $9.-) (183 pages)
There are moderate-sized tree trunks every thirty meters. They arise from greasy pits. Scattered over the surface are irregular salt-encrusted rims of drain-pipes disgorging droplets of water several meters across at the slightest rise in temperature. The inhabitants of this savanna are square in appearance and about the size of a shrew. They stretch and make a crackling sound and break into two individuals every half an hour or so. If you could look at your skin at an enlargement of 10000 times, this is how you would see your hairs, your openings of sweat glands and your bacteria. The healthy human skin is an ecosystem, just like a pond or a wood. In an environment of keratin soil with hairs and sweatgland discharge, a dense bacterial flora not only breaks down different components (causing, among other things, nasty smells) but also protects us against pathogenic species. On less healthy skins, we could find fleas, head- or crab lice drinking their blood meals, and sometimes even an itch mite taking great pains in burrowing just under the keratin layer. Other arthropods are found on healthy skins but are vectors of pathogenic organisms. On less populated or damaged skin the bacterium Staphylococcus aureus causes much destruction. Sometimes warts arise as a host action governed by a Papova virus. Much more happens on our skin, healthy or sick, and Andrews tells us about
TIBS
- February
47
1977
Top, dust mites (Dermatophagoides pteronissimq on human skin; under, closeup of front legs and jaws.
it in 183 very readable pages. It must be said that he has carefully digested the scientific reports of the different disciplines that study the skin. His book should be read by anyone interested in his very own microscopic pets ! J. VAN BRONSWIJK
J. van Bronswijk works in the Dermatology Depariment at the Academic Hospital in Utrecht. The Netherlands.
.Phenomenological overkill The Enzymes of Biological Membranes: Vol. 2, The Biosynthesis of Cell Components edited by Anthony Martonosi, published by Plenum Press, New York/London, 1976. $54.- (approx. &30.-) (xvii+651 pages)
The magnitude of this book, seventeen chapters in over 600 pages with almost 3000 citations, attests to the rapidly growing interest in research on membranes and membrane-bound enzymes. In spite of our developing understanding of the nature and properties of integral membrane proteins, however, work with enzymes of this class remains an art. Few such enzymes have been purified to homogeneity, and even assaying most of them in situ in the membrane is difficult. Finding the proper conditions for assay and isolation, often involving the judicious choice of detergent
or organic solvent, is still a matter of trial and error. The chapters of this book are, in effect, progress reports of many trials and errors with many different enzyme systems, from which one can retrieve specific information on specific enzymatic reactions. As such, the book will serve a useful function for research workers in fields closely related to the topics covered. The duration of usefulness will depend upon the speed of advances in each topic area, and at the pace of current research some of these articles may be outdated very soon. The book will not be useful to those hoping to gain new general insights into the problems ofmembrane structure and function, for no attempt was made to compare or contrast common features from different chapters. It is a pity that the dissemination of important and timely review articles such as those found in this book was not accomplished at a price more cornmensurate with their useful lifetime. Some of the chapters of the book cover topics with a very limited scope, where it was felt that suflicient information was available about a specific enzyme to warrant in-depth coverage. The article by Gennis and Strominger on the ‘C,,-Isoprenoid Alcohol Phosphokinase’ and that by Gennis and Hager on ‘Pyruvate Oxidase’ represent two enzymes which have been extensively purified. The first is obviously an integral membrane protein, requiring butanol for solubility and purilication, while the second is a water-soluble protein that is activated by association with lipid. Both are probable prototypes of other membrane enzymes and warrant inclusion in such a treatise, yet each chapter summarizes data primarily from only three research articles, and one could read the original almost as easily as the reviews. A chapter on ‘Glucose-6-phosphatase’ by Nordlie and Jorgenson, and a chapter on ‘Carnitine Palmitoyltransferase and Transport of Fatty Acids’ by Hoppel, cover adequately the rather extensive work on these enzymes, including effects of hormones and drugs on enzymatic activity. In both cases the enzymes are less well characterized. There is evidence that different forms may exist which may be related to orientation with respect to the membrane. A chapter by Brady and Fishman ‘Alterations of Galactosaminyland Galactosyltransferases in Cultured Mammalian Cells and in vivo’ outlines evidence for the loss of specific enzymes involved in ganglioside synthesis in the case of virus transformation in cultured cells on the one hand, and of a metabolic abnormality found in a 3+ month old infant on the other. The effect of detergents, lipid alteration by phospholipases, and temperature
on the kinetics of UDP-glucuronyltransferase are discussed extensively by Zakim and Vessey. This activity has not been purified sufficiently to establish that it is a single enzyme, and so the mechanistic conelusions drawn from kinetic data are unwarranted even though the data are interesting. At the other extreme of scope are two extensive review articles, one by Lands and Crawford on ‘Enzymes of Membrane Phosphlipid Metabolism in Animals’ and the other by Hussey and Baddiley on ‘Biosynthesis of Bacterial Cell Walls’. These chapters account for about 30”,, of the pages and citations of the entire book. The first is organized according to the type of bonds being formed or cleaved in phospholipid metabolism, while the latter considers both the structure and biosynthetic pathways for peptidoglycan, lipopolysaccharide, and teichoic acid. While both articles cover material that has been reviewed in one form or another previously, the broad scope and orientation of these articles, showing particular attention to membrane involvement where possible, do provide a valuable reference for those seeking information on these topics. The remaining articles cover an interesting variety of topics of intermediate scope. In most cases the emphasis is on biosynthetic pathways, with specific enzymes discussed where appropriate. Topics include mammalian ether-linked glycerolipids, glycoprotein biosynthesis, mammalian and plant sterol biosynthesis, plant fatty acid synthesis and metabolism, function of membrane-bound ribosomes in eukaryotic cells, and platelet membrane enzymes involved in hemostasis. A rather speculative article reviews evidence that bacteriophage T, infection of Escherichia coli involves several intermediates and processes that are associated with the bacterial cell envelope. In discussing the relationship between ‘latency’ of giucose-6-phosphatase and related activities to the morphology of the Nordlie and Jorgenson membrane, comment that ‘experimentation in this area presently appears stalled at the phenomenological stage’. One gets the impression that most work on membranebound enzymes is also still in the phenomenological stage, though hopefully not stalled there. Perhaps this collection of review articles will stir even greater activity in the search for general principles that will contribute to a better understanding of membrane structure and function. ROBLEY
LIGHT
Robley Light is Professor and Associate Chairman oJ the Department of Chemistry, Florida State University. Tallahassee, Florida, U.S.A.