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Neuropeptides and their peptidases
Biochimie 70 (1988) 1851- 1853 (~) Soci6t6 de Chimie biologique/Elsevier, Paris
1851
Book reviews
Fundamentals
of Endocrinology, by W. Roy Slaunwhite Jr., Vol. 1, Marcel Dekker Inc., 1988, pp. 440, US & Canada $45.00, $54.00 elsewhere Endocrinology is an old science• For some time, however, it remained mainly descriptive. But major concepts of molecular biology, namely receptors and second messengers; have totally renewed this area of research, which at present is one of the most up-todate fields in biology. Slaunwhite's book deliberately places endocrinology in its new perspective, as can be seen by a description of adenylate cyclase function in chapter 1. Chapter 2 is a summary of hormone types, and from chapter 3 onwards the text refers to physiology and specific hormonal controls: nutrition, nervous system, reproduction, and so on. This book is clearly designed not for confirmed scientists but rather for students following their first faculty courses. As such it is a good introduction to the most modern aspects of endocrinology. A. Danchin
with immunoglobulin probes or the diagnosis of monoclonality via somatic methylation-induced RFLP observed with some X probes in females. However, the interest of the book is considerable. For people involved in basic research, it is valuable to have access to the enormous amount of work that has been done on the isolation, detection, and specificity of tumors markers. What are they? What is their biochemistry or dosage method? And what are the limits of their specificity? Most of the data available on these "markers" will be of interest when cloned and mapped on human chromosomes. Some tumor markers already have clear clinical interest, for example, alpha-fetoprotein, which is too high in the blood of patients with liver tumors. Unfortunately, it may also be high in other circumstances, such as cirrhosis or hepatitis• Nevertheless this protein level is useful in the diagnosis of hepatoma. The various laboratories involved in the field of human tumor markers for diagnostic purposes will find in this book, beside the classical topics, the presentation of some uncommon models• For example, the c-myb proto-oncogene product in immature lymphoid, erythroid and myeloid cells is described. Cytogenetic data on solid tumors, with a cle~ turner specificity for some translocations, offer another example of an unusual tumor marker. T h l c h n n l r prov:des l,~h.okl . . . . . . . tO ,~ great of information on cancer data that is ordinarily scattered in different reviews and even libraries. This reason alone makes it of interest for many readers. •
Human Tumor Markers, edited by F. Cimino, G.D. Birkmayer, J.V. Klavins, E. Pimentel, F. Salvatore, de Gruyter, Berlin, New York, 1987, pp. 922, DM 380
..l~nl
A. Bernheim "It has been a dream of oncoiogists to find a simple test for diagnosing cancer• This dream has not yet come true." This statement by one of the editors of this volume explains why the last decade has seen an explosion of reports dealing with tumor markers, but with no significant breakthroughs, as the complexity and variation of human cancers have been underestimated. At the same time proto-oncogene activation and nonrandom-chromosomal abnormalities have been the hallmarks of certain specific models such as Burkitt's lymphoma or chronic myeloid leukemia. The 61 papers contained in this substantial volume are the proceedings of the Third International Congress of Human Tumor Markers, which was held in Lacco Ameno d'Ischia in April 1986. The topics are many and diverse. The organization of the book reflects this heterogeneity. Unfortunately, some recent methods for detection of neoplasia are lacking, such as the detection of a malignant clone
Neuropeptides and Their Peptidases, edited by A.J. Turner. VCH, Weinheim, Vol. 1, 1987, pp. 295, DM 156, US$ 93.50 Although a number of neuropeptides had been discovered and structurally characterized in the fifties, the era of neuropeptides began in the early seventies with the elucidation of the primary structure of substance P and of some of the hypothalamic factors. Then came the enkephalins, followed by an increasing number of peptides, totaling around 50. Neuropeptides may function as neurotransmitters, neuromodulators, or local hormones. In each case it is important that they should be removed from the
1852
B o o k reviews
extracellular space at various times after their release. Inactivation of the classical neurotransmitters, amines, and amino acids by high affinity uptake mechanisms is well known. No such uptake mechanisms exist for the neutopeptides, which have to be inactivated through degraaation by peptidases. This is quite similar to the inactivation of acetylcholine by acetylcholinesterase. The importance of peptidase in the inactivation processes of neuropeptides was originally put forward by Malfroy et al. ([1978] Nature 276, 523-526) with the demonstration that the inhibition of metalloendopeptidase 24.11, also called enkephalinase, by thiorpan led to an analgesic effect. (Roques et al., [1980] Nature 288,286-288). The use of peptidase inhibitors in.neuropsychopharmacology could follow the wide clinical application of the antihypertensjve agents captopril and enalapril, both potent inhibitors of angiotensin I converting enzyme (ACE). This enzyme concentrated in blood and lung is responsible for the formation of the vasopressor angiotensin II, and the degradation of the vasodilatator bradykinin. ACE is also present in the central nervous system where it could degrade various neuropeptides including various opioid peptides, neurotensin, substance P, LHRH, and so on. It is thus somewhat surprising that the administration of ACE inhibitors does not seem to modify brain function. It is now generally accepted that peptidases are never so specific and could be involved in the biosynthesis and degradation of a number of different peptides. It is therefore proposed to avoid the use of trivial names. The name metalloendopeptidase 24.11 would thus be preferred to enkephhlinase. This enzyme nomenclature is based on the general biochemical properties of each enzyme rather than on its physiological role. Turner's "Neuropeptides and their Peptidases" describes in depth the concept of neuropeptidases and their importance in brain function. It also contains reviews of the biosynthesis and molecular genetics of various peptides. It is a multi-author book with evidence of a strong editorial policy. The book is not thick (295 pp.), is quite readable, and the excellent work done by most of the authors is to be acknowledged. Some of the chapters are written like short stories, particularly the one by Ivell on the molecular biology of vasopressinergic and oxytocinergic cells. The chapter on peptidase inhibitors is full of important data. Several fully characterized peptidases are reviewed in depth, including ACE, metal!oendopeptidase 24.11, and calpains. What is missing :s a general critical review of the other various peptidase activities described so far in the brain. Admittedly, this field is difficult to review. Often, the enzyme activities described in "purified" preparations are due not to a single enzyme, but to a mixture of several enzymes (see for example the recent paper by Toffoletto et al., [1988] Biochem. J. 70, 47-56). The general confusion resulting from this situation will be
cleared up only by full characterization, including the purification to homogeneity, of the various activities. In summary, this book indicates clearly that the number of peptidases is not infinite; that the same enzyme could be located in peripheral organs as well as in the central nervous system; that the same enzyme could be involved in the degradation or formation of a large number of peptides with sometimes opposite functions, and m finally ~ that the neural specificities of peptidases are s.hown as much by their specific location as by their substrate specificities. Newcomers to the field, as well as specialists, will appreciate this book which I wholeheartedly recommend as the best monography available in this exciting domain. M. Rossier
Flavins and Flavoproteins, edited by D.E. Edmondson & D.B. McCormick, de Gruyter, Vol. I, 1987, pp. 775 Since the discovery of the first yellow enzyme by Warburg and Christian in 1932 and the synthesis of lumiflavin by Richard Kuhn in 1934, the field of isolated flavins and flavoproteins has become increasingly important. Flavin enzymes are essential components of all biological redox chains. The reactive group, the isoalloxazine ring, nearly always remains the same (with a few exceptions), although in some cases it is covalently bound to the protein. This group can exist in 3 redox states and is able to covalently bind specific reactants that are substrate analogs. One characteristic of ravin coenzymes as compared to other electron carriers - - heme, iron-sulfur complexes, and nicotinamide coenzymes - - is the versatility of ravin in accepting a n d / o r donating either one electron as cytochromic heme or two electrons as NAD(H); this possibility relies on the high stabilization of the semiquinone form that can be afforded by certain apoproteins. The modulation of isoalloxazine properties by the surrounding binding pocket leads to 3 major classes of behavior: dehydrogenases, 1 electron transferases, and oxygen activation (oxidases or hydroxyla-
ses).
The main issue in the flavoprotein field has been and remains the establishment of the precise correlation between the class of property / double substrate specificity (donor and acceptor) and the relevant structural features of the binding pocket. Since 1966, when the first symposium on Flavins and Flavoproteins took place in Amsterdam, developments in the field have been kept up to date every
1851
Book reviews
Fundamentals
of Endocrinology, by W. Roy Slaunwhite Jr., Vol. 1, Marcel Dekker Inc., 1988, pp. 440, US & Canada $45.00, $54.00 elsewhere Endocrinology is an old science• For some time, however, it remained mainly descriptive. But major concepts of molecular biology, namely receptors and second messengers; have totally renewed this area of research, which at present is one of the most up-todate fields in biology. Slaunwhite's book deliberately places endocrinology in its new perspective, as can be seen by a description of adenylate cyclase function in chapter 1. Chapter 2 is a summary of hormone types, and from chapter 3 onwards the text refers to physiology and specific hormonal controls: nutrition, nervous system, reproduction, and so on. This book is clearly designed not for confirmed scientists but rather for students following their first faculty courses. As such it is a good introduction to the most modern aspects of endocrinology. A. Danchin
with immunoglobulin probes or the diagnosis of monoclonality via somatic methylation-induced RFLP observed with some X probes in females. However, the interest of the book is considerable. For people involved in basic research, it is valuable to have access to the enormous amount of work that has been done on the isolation, detection, and specificity of tumors markers. What are they? What is their biochemistry or dosage method? And what are the limits of their specificity? Most of the data available on these "markers" will be of interest when cloned and mapped on human chromosomes. Some tumor markers already have clear clinical interest, for example, alpha-fetoprotein, which is too high in the blood of patients with liver tumors. Unfortunately, it may also be high in other circumstances, such as cirrhosis or hepatitis• Nevertheless this protein level is useful in the diagnosis of hepatoma. The various laboratories involved in the field of human tumor markers for diagnostic purposes will find in this book, beside the classical topics, the presentation of some uncommon models• For example, the c-myb proto-oncogene product in immature lymphoid, erythroid and myeloid cells is described. Cytogenetic data on solid tumors, with a cle~ turner specificity for some translocations, offer another example of an unusual tumor marker. T h l c h n n l r prov:des l,~h.okl . . . . . . . tO ,~ great of information on cancer data that is ordinarily scattered in different reviews and even libraries. This reason alone makes it of interest for many readers. •
Human Tumor Markers, edited by F. Cimino, G.D. Birkmayer, J.V. Klavins, E. Pimentel, F. Salvatore, de Gruyter, Berlin, New York, 1987, pp. 922, DM 380
..l~nl
A. Bernheim "It has been a dream of oncoiogists to find a simple test for diagnosing cancer• This dream has not yet come true." This statement by one of the editors of this volume explains why the last decade has seen an explosion of reports dealing with tumor markers, but with no significant breakthroughs, as the complexity and variation of human cancers have been underestimated. At the same time proto-oncogene activation and nonrandom-chromosomal abnormalities have been the hallmarks of certain specific models such as Burkitt's lymphoma or chronic myeloid leukemia. The 61 papers contained in this substantial volume are the proceedings of the Third International Congress of Human Tumor Markers, which was held in Lacco Ameno d'Ischia in April 1986. The topics are many and diverse. The organization of the book reflects this heterogeneity. Unfortunately, some recent methods for detection of neoplasia are lacking, such as the detection of a malignant clone
Neuropeptides and Their Peptidases, edited by A.J. Turner. VCH, Weinheim, Vol. 1, 1987, pp. 295, DM 156, US$ 93.50 Although a number of neuropeptides had been discovered and structurally characterized in the fifties, the era of neuropeptides began in the early seventies with the elucidation of the primary structure of substance P and of some of the hypothalamic factors. Then came the enkephalins, followed by an increasing number of peptides, totaling around 50. Neuropeptides may function as neurotransmitters, neuromodulators, or local hormones. In each case it is important that they should be removed from the
1852
B o o k reviews
extracellular space at various times after their release. Inactivation of the classical neurotransmitters, amines, and amino acids by high affinity uptake mechanisms is well known. No such uptake mechanisms exist for the neutopeptides, which have to be inactivated through degraaation by peptidases. This is quite similar to the inactivation of acetylcholine by acetylcholinesterase. The importance of peptidase in the inactivation processes of neuropeptides was originally put forward by Malfroy et al. ([1978] Nature 276, 523-526) with the demonstration that the inhibition of metalloendopeptidase 24.11, also called enkephalinase, by thiorpan led to an analgesic effect. (Roques et al., [1980] Nature 288,286-288). The use of peptidase inhibitors in.neuropsychopharmacology could follow the wide clinical application of the antihypertensjve agents captopril and enalapril, both potent inhibitors of angiotensin I converting enzyme (ACE). This enzyme concentrated in blood and lung is responsible for the formation of the vasopressor angiotensin II, and the degradation of the vasodilatator bradykinin. ACE is also present in the central nervous system where it could degrade various neuropeptides including various opioid peptides, neurotensin, substance P, LHRH, and so on. It is thus somewhat surprising that the administration of ACE inhibitors does not seem to modify brain function. It is now generally accepted that peptidases are never so specific and could be involved in the biosynthesis and degradation of a number of different peptides. It is therefore proposed to avoid the use of trivial names. The name metalloendopeptidase 24.11 would thus be preferred to enkephhlinase. This enzyme nomenclature is based on the general biochemical properties of each enzyme rather than on its physiological role. Turner's "Neuropeptides and their Peptidases" describes in depth the concept of neuropeptidases and their importance in brain function. It also contains reviews of the biosynthesis and molecular genetics of various peptides. It is a multi-author book with evidence of a strong editorial policy. The book is not thick (295 pp.), is quite readable, and the excellent work done by most of the authors is to be acknowledged. Some of the chapters are written like short stories, particularly the one by Ivell on the molecular biology of vasopressinergic and oxytocinergic cells. The chapter on peptidase inhibitors is full of important data. Several fully characterized peptidases are reviewed in depth, including ACE, metal!oendopeptidase 24.11, and calpains. What is missing :s a general critical review of the other various peptidase activities described so far in the brain. Admittedly, this field is difficult to review. Often, the enzyme activities described in "purified" preparations are due not to a single enzyme, but to a mixture of several enzymes (see for example the recent paper by Toffoletto et al., [1988] Biochem. J. 70, 47-56). The general confusion resulting from this situation will be
cleared up only by full characterization, including the purification to homogeneity, of the various activities. In summary, this book indicates clearly that the number of peptidases is not infinite; that the same enzyme could be located in peripheral organs as well as in the central nervous system; that the same enzyme could be involved in the degradation or formation of a large number of peptides with sometimes opposite functions, and m finally ~ that the neural specificities of peptidases are s.hown as much by their specific location as by their substrate specificities. Newcomers to the field, as well as specialists, will appreciate this book which I wholeheartedly recommend as the best monography available in this exciting domain. M. Rossier
Flavins and Flavoproteins, edited by D.E. Edmondson & D.B. McCormick, de Gruyter, Vol. I, 1987, pp. 775 Since the discovery of the first yellow enzyme by Warburg and Christian in 1932 and the synthesis of lumiflavin by Richard Kuhn in 1934, the field of isolated flavins and flavoproteins has become increasingly important. Flavin enzymes are essential components of all biological redox chains. The reactive group, the isoalloxazine ring, nearly always remains the same (with a few exceptions), although in some cases it is covalently bound to the protein. This group can exist in 3 redox states and is able to covalently bind specific reactants that are substrate analogs. One characteristic of ravin coenzymes as compared to other electron carriers - - heme, iron-sulfur complexes, and nicotinamide coenzymes - - is the versatility of ravin in accepting a n d / o r donating either one electron as cytochromic heme or two electrons as NAD(H); this possibility relies on the high stabilization of the semiquinone form that can be afforded by certain apoproteins. The modulation of isoalloxazine properties by the surrounding binding pocket leads to 3 major classes of behavior: dehydrogenases, 1 electron transferases, and oxygen activation (oxidases or hydroxyla-
ses).
The main issue in the flavoprotein field has been and remains the establishment of the precise correlation between the class of property / double substrate specificity (donor and acceptor) and the relevant structural features of the binding pocket. Since 1966, when the first symposium on Flavins and Flavoproteins took place in Amsterdam, developments in the field have been kept up to date every