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An introduction to human biochemistry
Cell, Vol. 20, 567-575,
June
1980.
Copyright
0 1980
by MIT
Book Reviews
Starting Out in Biochemistry
An Introduction to Human By C. A. Pasternak. Oxford: Oxford University (softcover).
Biochemistry. Press.
271
pp.
$15.95
C. A. Pasternak is the Head of the Department of Biochemistry at St. George’s Hospital Medical School, University of London. He has written a biochemistry text for first-year medical students, designed “to present in one volume the biochemistry and cell biology necessary for an understanding of the molecular basis of medicine.” Do we need another such textbook? The field is already replete with books designed for similar purposes. This reviewer is certainly willing to concede that the field is open to new authors. For one thing, such texts satisfy certain parochial needs. The firstyear medical student whom Pasternak has in mind is a different breed from his U.S. counterpart. The British student goes straight from high school to medical school. In the United States there is a 3 to 4-year interval for general undergraduate studies, often completed by the award of a bachelor’s degree before entry into medical school. The entering U.S. medical student will therefore often have had significant prior exposure to biochemistry. Other countries have still different practices, so that no single text could serve all types of medical student. Another reason for conceding that it is open house as far as potential authors are concerned is my belief that a truly successful text dealing with the biochemistry of organ systems has yet to be written. The problem here is one of defining what is meant by biochemistry. A book such as Stryer’s Biochemistry is a powerful ally of the biochemistry instructor. It makes compulsive, enthralling reading. The student cannot fail to become impressed with the excitement of biochemistry and its relevance to medicine. However, Stryer stops far short of covering what, in many schools, is the section of the preclinical curriculum assigned to the department of biochemistry. The missing section is systemic biochemistry. The variability in the length and coverage of the biochemistry curriculum in U.S. medical schools was brought home vividly when I recently took part in a survey of medical schools in the United States and Canada concerning the amount of biochemistry teaching and the topics covered. The lecture hours taught varied over a 4 fold range from a minimum of 35 to a maximum of 139. Obviously the school with the smallest number of hours was not teaching the same curriculum as that with the greatest number of hours. The differences stemmed largely from whether subjects
additional to basic biochemistry were taught. This is not to say that these additional topics, among which the biochemistry of organs and tissues is the most prominent, are not covered within the preclinical curriculum as a whole. It is simply that in different schools, for various reasons-many of which are accidents of history-the subject matter may be covered in the other basic science departments. Correspondingly, the topics may be covered in other kinds of textbooks such as pathophysiology. Pasternak has taken the line that he should be comprehensive across the areas of basic biochemistry and organ system biochemistry. Within a relatively compact format he has attempted to provide a broad general coverage under two main headings. A first section on “cellular potentiality” covers mainly basic biochemistry, while “cellular specialization” covers systemic biochemistry. The scope of the book and the logic behind it are commendable. The format is attractive, the diagrams are clear and there are generally the makings of an adequate textbook. I cannot recommend this book, however, on account of the significant number of very serious errors, some of which follow. It is stated on p. 3 that “all amino acids have the L(+) configuration about the #, or C-2, carbon atom.” The reference is to the naturally occurring amino acids found in proteins and is contradicted by the fact that the L stereoisomers of leucine, phenylalanine, histidine, methionine, serine, proline, threonine and tryptophan all have the (--) configuration. Glycogen is ‘soluble only in boiling alkali” (p. 30). The cyclic AMP-activated protein kinase is said, incorrectly, to be the enzyme that converts inactive phosphorylase into phosphorylase (p. 31). The gluconeogenic pathway from lactate to glucose is drawn in a way that implies that pyruvate is not part of the pathway (p. 34). An enzyme that does not exist is said to convert galactose i-phosphate into UDP galactose and is claimed to be the missing enzyme in the hereditary disorder galactosemia (p. 35). The urea cycle enzymes are not all “in mitochondria” (p. 40) and to say that three molecules of ATP are required for the synthesis of a molecule of urea (p. 98) is misleading when the requirement is for four high energy phosphate groups. The branching enzyme that participates in glycogen synthesis “utilizes UDP glucose” (p. 69). Cyclic AMP rather than AMP is listed as a regulator of phosphorylase activity (p. 78). Red cells are said to be necessary for the formation of a blood clot (p. 166); they are not. The corpus luteum has been placed in the uterus (p. 196) instead of the ovary, and so on. One is also disappointed that in a book ot thus nature there should apparently be no mention of cytochrome PdsO and the mixed-function oxidases or of ketosis. It is both regrettable and surprising that these errors should have seen the light of day. If a second edition
Cell 568
is contemplated, a drastic content will be required. W. J. Whelan Department of Biochemistry University of Miami School Miami, Florida 33101
lsozymes
overhaul
of the factual
of Medicine
One by One
Isozymes. Current Topics in Biology and Medicine, 3. M. C. Rattazzi, J. G. Scandalios and G. S. Whitt, eds. New York: Alan R. Liss. 215 pp. $22.00.
Volume 3 lives up to the general theme of this relatively new series in presenting diverse perspectives of new concepts and technologies in isozyme research. This volume contains six different contributions ranging from the clinical diagnostic use of creatine kinase isozymes to isozyme molecular structure and genetic variation. The first chapter (J. M. McCord) reviews superoxide dismutases. These ubiquitous enzymes, essential to all higher forms of life, seem to have evolved from two ancestral genomes into three distinct structural types. The three isozymes are classified on the basis of their metal components as the cuprozinc, manganese and iron forms. The species distribution of the isozymes has been puzzling for years, but it now appears that eucaryotes contain both the manganese and the cuprozinc enzymes while procaryotes contain the iron and manganese forms. The structure of the cuprozinc isozyme has been characterized in most detail, and McCord reviews the primary, secondary and tertiary structure of the enzyme as well as the metal and substrate binding sites and functions. The manganese-containing isozyme has been isolated from numerous sources but is less well characterized. The iron-containing superoxide dismutase has been isolated from several procaryotes, and sequence analysis reveals a striking homology with the manganesecontaining form. The physiological function of the superoxide dismutases appears to be protection against oxygen (superoxide) toxicity. Strict obligate anaerobes do not produce the enzyme, and the levels of the enzyme in mutants of E. coli, which differ in their ability to tolerate oxygen, support these views. Similar studies in mammals also corroborate this physiological function.
The second selection (G. C. Bewley and S. Miller) deals with the origin and differentiation of cY-glycerophosphate dehydrogenase ((uGPDH) isozymes in Drosophila. The enzyme exists in three electrophoretic forms. aGPDH-1 (highest anodial migration) represents an adult-specific isozyme. (rGPD-3 exists in larval development and increases in amount during the third instar of development. The level of the enzyme then declines to very low levels concomitant with the formation of aGPDH-1. Each isozyme is also distinct with respect to tissue localization, with over 50% of aGPD-3 in the fat body (analogous to liver). On the other hand, aGPD-1 seems to predominate in thoracic flight muscle. aGPD-2 is judged to be a hybrid of lower concentration and of lesser metabolic importance. The authors point out that the enzyme serves at a central point for the coupling of carbohydrate and lipid metabolism. The authors review a variety of kinetic data which distinguish the physiological functions of aGPDH-3 and aGPDH-1, suggesting that the two major isoenzymes have distinct metabolic roles. aGPDH-1 functions both to provide a-glycerophosphate, whose oxidation is linked to ATP generation by a-glycerophosphate oxidase in the mitochondria, and to provide oxidized pyridine nucleotides essential for continued glycolysis. aGPDH-3 is believed to be the primary enzyme regulating the NAD+/NADH ratio (in contrast to LDH) and providing a-glycerophosphate for phospholipid synthesis. Structural analysis of the purified isozymes, including comparative peptide fingerprinting and genetic and immunological analysis, indicates no apparent differences in the primary structures. The authors conclude that while the aGPDH isozymes in higher mammals are due to multiple cistrons, the multiple forms observed in Drosophila are due to some type of post-synthetic modification of a single gene product. R. S. Holmes and C. J. Masters contribute the third chapter of this volume, which deals with the subcellular localization of isozymes. This is one of the most general presentations of the volume and is thus most likely to be read by nonisozymers. The authors review particular cases of cytoplasmic, nuclear, mitochondrial, microsomal, peroxisomal and lysosomal-specific isozymes. The authors also consider microlocalization of cytosolic enzymes including the concept of glycolytic complex. The potential for regulation by metabolites is discussed with respect to release of enzymes from membranes and alteration of catalytic properties upon release from membrane on macromolecular complexes. Finally, the authors consider the techniques for analyzing subcellular localization and macromolecular interactions. They conclude that current evidence suggests that differential subcellular localization of isozymes may be viewed as a general expectation rather than an exception. R. Roberts’ contribution on creatine kinase (CK) and diagnosis of myocardial infarction is clearly the
June
1980.
Copyright
0 1980
by MIT
Book Reviews
Starting Out in Biochemistry
An Introduction to Human By C. A. Pasternak. Oxford: Oxford University (softcover).
Biochemistry. Press.
271
pp.
$15.95
C. A. Pasternak is the Head of the Department of Biochemistry at St. George’s Hospital Medical School, University of London. He has written a biochemistry text for first-year medical students, designed “to present in one volume the biochemistry and cell biology necessary for an understanding of the molecular basis of medicine.” Do we need another such textbook? The field is already replete with books designed for similar purposes. This reviewer is certainly willing to concede that the field is open to new authors. For one thing, such texts satisfy certain parochial needs. The firstyear medical student whom Pasternak has in mind is a different breed from his U.S. counterpart. The British student goes straight from high school to medical school. In the United States there is a 3 to 4-year interval for general undergraduate studies, often completed by the award of a bachelor’s degree before entry into medical school. The entering U.S. medical student will therefore often have had significant prior exposure to biochemistry. Other countries have still different practices, so that no single text could serve all types of medical student. Another reason for conceding that it is open house as far as potential authors are concerned is my belief that a truly successful text dealing with the biochemistry of organ systems has yet to be written. The problem here is one of defining what is meant by biochemistry. A book such as Stryer’s Biochemistry is a powerful ally of the biochemistry instructor. It makes compulsive, enthralling reading. The student cannot fail to become impressed with the excitement of biochemistry and its relevance to medicine. However, Stryer stops far short of covering what, in many schools, is the section of the preclinical curriculum assigned to the department of biochemistry. The missing section is systemic biochemistry. The variability in the length and coverage of the biochemistry curriculum in U.S. medical schools was brought home vividly when I recently took part in a survey of medical schools in the United States and Canada concerning the amount of biochemistry teaching and the topics covered. The lecture hours taught varied over a 4 fold range from a minimum of 35 to a maximum of 139. Obviously the school with the smallest number of hours was not teaching the same curriculum as that with the greatest number of hours. The differences stemmed largely from whether subjects
additional to basic biochemistry were taught. This is not to say that these additional topics, among which the biochemistry of organs and tissues is the most prominent, are not covered within the preclinical curriculum as a whole. It is simply that in different schools, for various reasons-many of which are accidents of history-the subject matter may be covered in the other basic science departments. Correspondingly, the topics may be covered in other kinds of textbooks such as pathophysiology. Pasternak has taken the line that he should be comprehensive across the areas of basic biochemistry and organ system biochemistry. Within a relatively compact format he has attempted to provide a broad general coverage under two main headings. A first section on “cellular potentiality” covers mainly basic biochemistry, while “cellular specialization” covers systemic biochemistry. The scope of the book and the logic behind it are commendable. The format is attractive, the diagrams are clear and there are generally the makings of an adequate textbook. I cannot recommend this book, however, on account of the significant number of very serious errors, some of which follow. It is stated on p. 3 that “all amino acids have the L(+) configuration about the #, or C-2, carbon atom.” The reference is to the naturally occurring amino acids found in proteins and is contradicted by the fact that the L stereoisomers of leucine, phenylalanine, histidine, methionine, serine, proline, threonine and tryptophan all have the (--) configuration. Glycogen is ‘soluble only in boiling alkali” (p. 30). The cyclic AMP-activated protein kinase is said, incorrectly, to be the enzyme that converts inactive phosphorylase into phosphorylase (p. 31). The gluconeogenic pathway from lactate to glucose is drawn in a way that implies that pyruvate is not part of the pathway (p. 34). An enzyme that does not exist is said to convert galactose i-phosphate into UDP galactose and is claimed to be the missing enzyme in the hereditary disorder galactosemia (p. 35). The urea cycle enzymes are not all “in mitochondria” (p. 40) and to say that three molecules of ATP are required for the synthesis of a molecule of urea (p. 98) is misleading when the requirement is for four high energy phosphate groups. The branching enzyme that participates in glycogen synthesis “utilizes UDP glucose” (p. 69). Cyclic AMP rather than AMP is listed as a regulator of phosphorylase activity (p. 78). Red cells are said to be necessary for the formation of a blood clot (p. 166); they are not. The corpus luteum has been placed in the uterus (p. 196) instead of the ovary, and so on. One is also disappointed that in a book ot thus nature there should apparently be no mention of cytochrome PdsO and the mixed-function oxidases or of ketosis. It is both regrettable and surprising that these errors should have seen the light of day. If a second edition
Cell 568
is contemplated, a drastic content will be required. W. J. Whelan Department of Biochemistry University of Miami School Miami, Florida 33101
lsozymes
overhaul
of the factual
of Medicine
One by One
Isozymes. Current Topics in Biology and Medicine, 3. M. C. Rattazzi, J. G. Scandalios and G. S. Whitt, eds. New York: Alan R. Liss. 215 pp. $22.00.
Volume 3 lives up to the general theme of this relatively new series in presenting diverse perspectives of new concepts and technologies in isozyme research. This volume contains six different contributions ranging from the clinical diagnostic use of creatine kinase isozymes to isozyme molecular structure and genetic variation. The first chapter (J. M. McCord) reviews superoxide dismutases. These ubiquitous enzymes, essential to all higher forms of life, seem to have evolved from two ancestral genomes into three distinct structural types. The three isozymes are classified on the basis of their metal components as the cuprozinc, manganese and iron forms. The species distribution of the isozymes has been puzzling for years, but it now appears that eucaryotes contain both the manganese and the cuprozinc enzymes while procaryotes contain the iron and manganese forms. The structure of the cuprozinc isozyme has been characterized in most detail, and McCord reviews the primary, secondary and tertiary structure of the enzyme as well as the metal and substrate binding sites and functions. The manganese-containing isozyme has been isolated from numerous sources but is less well characterized. The iron-containing superoxide dismutase has been isolated from several procaryotes, and sequence analysis reveals a striking homology with the manganesecontaining form. The physiological function of the superoxide dismutases appears to be protection against oxygen (superoxide) toxicity. Strict obligate anaerobes do not produce the enzyme, and the levels of the enzyme in mutants of E. coli, which differ in their ability to tolerate oxygen, support these views. Similar studies in mammals also corroborate this physiological function.
The second selection (G. C. Bewley and S. Miller) deals with the origin and differentiation of cY-glycerophosphate dehydrogenase ((uGPDH) isozymes in Drosophila. The enzyme exists in three electrophoretic forms. aGPDH-1 (highest anodial migration) represents an adult-specific isozyme. (rGPD-3 exists in larval development and increases in amount during the third instar of development. The level of the enzyme then declines to very low levels concomitant with the formation of aGPDH-1. Each isozyme is also distinct with respect to tissue localization, with over 50% of aGPD-3 in the fat body (analogous to liver). On the other hand, aGPD-1 seems to predominate in thoracic flight muscle. aGPD-2 is judged to be a hybrid of lower concentration and of lesser metabolic importance. The authors point out that the enzyme serves at a central point for the coupling of carbohydrate and lipid metabolism. The authors review a variety of kinetic data which distinguish the physiological functions of aGPDH-3 and aGPDH-1, suggesting that the two major isoenzymes have distinct metabolic roles. aGPDH-1 functions both to provide a-glycerophosphate, whose oxidation is linked to ATP generation by a-glycerophosphate oxidase in the mitochondria, and to provide oxidized pyridine nucleotides essential for continued glycolysis. aGPDH-3 is believed to be the primary enzyme regulating the NAD+/NADH ratio (in contrast to LDH) and providing a-glycerophosphate for phospholipid synthesis. Structural analysis of the purified isozymes, including comparative peptide fingerprinting and genetic and immunological analysis, indicates no apparent differences in the primary structures. The authors conclude that while the aGPDH isozymes in higher mammals are due to multiple cistrons, the multiple forms observed in Drosophila are due to some type of post-synthetic modification of a single gene product. R. S. Holmes and C. J. Masters contribute the third chapter of this volume, which deals with the subcellular localization of isozymes. This is one of the most general presentations of the volume and is thus most likely to be read by nonisozymers. The authors review particular cases of cytoplasmic, nuclear, mitochondrial, microsomal, peroxisomal and lysosomal-specific isozymes. The authors also consider microlocalization of cytosolic enzymes including the concept of glycolytic complex. The potential for regulation by metabolites is discussed with respect to release of enzymes from membranes and alteration of catalytic properties upon release from membrane on macromolecular complexes. Finally, the authors consider the techniques for analyzing subcellular localization and macromolecular interactions. They conclude that current evidence suggests that differential subcellular localization of isozymes may be viewed as a general expectation rather than an exception. R. Roberts’ contribution on creatine kinase (CK) and diagnosis of myocardial infarction is clearly the