832
Book Reviews
both, the interfacial activation is regarded as a direct consequence of the hpiddwater interface on the conformation of the enzyme. While gastric lipase is responsible for fat hydrolysis in the stomach, pancreatic lipase hydrolyses the water insoluble triacylglycerols in the intestinal lumen. Inhibition of pancreatic lipase by bile salts is relieved by the cofactor colipase, which is thought to work by binding to the surface of the lipid and increasing the enzyme’s affinity for its substrate. Inhibition of the human enzyme is of particular medical interest as a reduction of fatty acid absorption is potentially useful for the treatment of obesity. Tetrahydrolipastatin (THL), a potent inhibitor of human pancreatic lipase, is currently undergoing clinical trials. However, the actual mechanism of pancreatic lipase is poorly understood. In this book, X-ray analysis of the crystal structures of three different lipases, Rhizomucor miehei, Geotrichum candidum and human pancreatic lipase, show the presence of structural features not predictable from primary sequences and give new functional insights into the reaction mechanisms of the enzymes. There is evidence for a large conformational change by a structural ‘flap’, which moves away from the active site region to generate room for the triglyceride substrate upon interfacial activation. The kinetics of lipase action are discussed, with particular reference to gastric lipase. The medical applications of finding hpase inhibitors are numerous and are dealt with in Chapters 10 and 15 of the book in relation to the quest for drug design in cardiovascular disease and others. Chapter 12 gives a survey of purification processes for lipases, followed by a discussion of their industrial applications, particularly in organic synthesis. The study of lipases has been greatly enhanced by progression in recombinant technology and the availability of three-dimensional structures determined at high resolution by X-ray crystallography. Lipases are heavily used in industry for hydrolysis of ester linkages of mono-, di-, and triglycerides in processes such as soap production and removal of fat from fabrics, machinery and water. Thus, the advantages of being able to structurally modify the specificity and optimum activity conditions of lipases are clearly apparent. The book draws to a close with a discussion of the current work based on the modification of the structure of lipases, which is likely to undergo rapid expansion as the natural properties of the enzymes are exploited by the protein engineer. Conlenis Sequence comparisons within the lipase family, A. Suendsen. A sequence analysis of lipases, esterases and related proteins, S. B. Petersen and F. Drablos. Lipases from plants, K. D. Mukherjee and M. J. Hills. The three dimensional structures of two lipases from filamentous fungi, D. M. Lawson, A. M. Brzozowski, G. G. Dodson, R. E. Hubbard,
B. Huge-Jensen,
E. Boel and 2. S. Derewenda.
Structural aspects of phospholipase C from Bacillus cereus and its reaction mechanism, E. Hough and S. Hansen. Phospholipase AZ: mechanism and structure, H. M. Verheij and B. W. Dijkstra. Structure and mechanism of human pancreatic lipase, F. W. Winkler and K. Gubernator. Kinetics of triglyceride lipases, M. Martinelle and K. Hub. Gastric lipases: cellular, biochemical and kinetic aspects, F. Carriere, Y. Gargouri, and R. Verger. Lipase
H. Moreau,
S. Ransca,
E. Rogalska
inhibitors, S. Patkar and F. Bj6rkling. Substrates from phospholipse C and sphingomyelinase from Bacihus cereus, relation between chemical structure and
enzyme hydrolysis, U. Massing and H. Eibl. Isolation and purification of hpases, M. R. Aires-Barros, M. A. Taipu and M. S. Cabral. Industrial applications of lipases, E. ,N. Vulfson. Lipaeses and phospholipases in organic synthesis, J. Mfting and H. Eibl. Medical aspects of triglyceride hpases, G. Bengtsson-Olirecronu and T. Olirecrona. Protein engineering of hpases, R. Bott. J. W. Shield and A. J. Poulose. Index. Biochemical, Pharmacological and Clinical Aspects of Nitric Oxide B. A. Weissman, N. AIIon and S. Shapira (Eds). Plenum Press. Price $79.50 (Prices are 20% higher outside U.S.A. and Canada), ISBN 0-306-45113-l.
In 1992 Science named Nitric Oxide (NO) Molecule of the Year. This, and the fact that nitric oxide is mentioned in over fifty scientific publications weekly, is hardly surprising considering its involvement in macrophage host killing, control of blood pressure, long-term potentiation in memory consolidation, impotence and inter- and intracellular signalling among other processes. Nitric oxide is now recognised to be a key vasodilator produced by endothelial cells. It mediates its effects through the nitric oxide cyclic GMP (cGMP) signal transduction mechanism. In vascular smooth muscle cells a nitric oxide-induced increase in cGMP concentration inhibits phospholipase C activity resulting in altered phosphorylation of endogenous proteins including myosin light chain, which is dephosphorylated with subsequent smooth muscle relaxation. In lymphocytes, nitric oxide has been shown to directly activate p21’““. This book is designed to act as a stepping stone for scientists entering the field of nitric oxide, and it centres on certain aspects of nitric oxide biochemistry and pharmacology, particularly synthesis-related issues involving nitric oxide synthase (NOS). It is easy to read and consists of short, informative articles, which are well referenced and indexed. Brief
contents
Chemistry and biochemistry of nitric oxide, Pharmacology of drug development, Nitric oxide and the respiratory and cardiovascular systems, Nitric oxide and brain functions, Subject index, Author index.
Enzymes of the Cholinesterase Family D. M. Quinn, A. S. Balasubramaaian, B. P. Doctor and P. Taylor (Eds). Plenum Publishing Corporation. Price $129.50 domestic (Prices are 20% higher outside U.S.A. and Canada), ISBN 0-30645I35-2.
This book is a compilation of presentations from the 5th International Meeting on Cholinesterases in Madras, India, September 1994, describing recent investigations of the structure, function, and molecular and cellular biology of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and related enzymes. Acetylcholinesterase is the best studied of the group of enzymes. It has important implications in agricultural insect control, and acetylcholinesterase inhibitors are being sought to treat the disfunctions in the central nervous system associated with Alzheimer’s disease. In addition, as acetylcholinesterase is the target for biological warfare
833
Book Reviews agents like nerve gases, the military forces take considerable interest in the enzyme. The book is divided into five sections, and contains 54 poster abstracts in addition to 54 oral presentation summaries, which cover the rapidly advancing fields of cell and molecular biology of the cholinesterases. In particular, the topics of the relationship between acetylcholinesterase gene structure and the various forms of the enyzme, mechanisms of gene expression, cellular biosynthesis, assembly and non-catalytic roles of cholinesterases are covered. Contents
Gene structure and expression of cholinesterases, Polymorphism and structure of cholinesterases, Mechanism of catalysis of cholinesterase, Cellular biology of cholinesterases, Structure-function relationships of anticholinesterase agents, Noncholinergic functions of cholinesterases, Pharmacological utilization of anticholinesterases, Appendices. Biochemistry J. Dow,
Molecules,
G. Lindsay
Longman. Price f25.95,
Cells
and the Body
and J. Morrison. ISBN
Addison
Wesley
0201631873.
The purpose of this book is to provide a concise compendium of biochemical and molecular biology issues relevant to students of medicine and related disciplines. It focuses primarily on those issues that are directly involved with the workings of the human body and its response to disease. The book is beautifully illustrated, progressing from the molecular, through the cellular level to consideration of individual organs, eventually resulting in discussion of the entire body and its attempts to defend itself from disease. Extensive cross referencing to ‘whole body’ and ‘molecular’ subjects throughout emphasizes the importance of knowledge of diverse scientific disciplines to the practice of medicine. Numerous diagrams, tables and boxes of classical and historical information make this book a pleasure to read rather than merely reference material. In a welcome move, continual reference to Escherichia coli has been ommitted because of a more comprehensive understanding of eukaryotic systems, in particular humans. Biochemistry is an impressive publication, and will provide the ‘core’ knowledge of biochemistry and molecular biology upon which medical students can continue to expand their particular areas of interest. Brief
contents
Preface. Acknowledgements. Chapter 1: Biochemistry, biology and medicine. Chapter 2: Small molecules. Chapter 3: Cells, organelles and membranes. Chapter 4: Proteins as functional units: sequence, structure and modification. Chapter 5: Genes and their expression: RNA in the generation and translation of messages. Chapter 6: DNA as the store of biological information: the nature and replication of genomes. Chapter 7: An introduction to metabolic processes and energy production in mitochondria. Chapter 8: The metabolism of glucose: storage and energy generation. Chapter 9: Lipid metabolism. Chapter 10: Metabolism of nitrogen-containing molecules. Chapter 11: Communication between cells and tissues: hormone transmitters and growth factors. Chapter 12: Blood: molecular functions of cells and plasma. Chapter 13: The
molecular and metabolic activities of multicellular tissues. Chapter 14: From food to energy: molecular aspects of digestion and nutrition. Chapter 15: The structural tissues. Chapter 16: Immunoglobulins and defence mechanisms of the body. Chapter 17: The molecular genetic basis of disease. Chapter 18: Invaders of the body. Index. The Antibodies: Volume I Maurizio Zanetti and J. Donald Capta (Eds). Harwood Academic Publishers. Prices $85.00, f52.00 Hardback, ISBN 3-7186-0602-X. $60.00, f36.00. Paperback. ISBN 3-7186-0610-O.
Antibodies continue to remain at the forefront of immunology and the biomedical sciences owing to the recent advances in the use of monoclonal antibodies and the major implications of antibody engineering in both drug design and diagnosis. This volume provides an integrated view of antibody structure, function, diversity and synthesis in relation to genetic manipulation of antibodies, immunoglobulin engineering, phage display of antibody fragments and minibody repertoires. Chapters are supported by highly detailed tables and figures, in particular several ribbon, space tilling and composite models of the structural domains of immunoglobulins and their interactions. Exhaustive reference lists follow each discussion. Contents
V(D)J recombination, class switching and somatic mutation in human immunoglobulin minilocus transgenic mice, N. Tuaillon and J. D. Capra. Three dimensional aspects of IGg structure and function, A. B. Edmundson, L. W. Guddet,
R. A. Rosauer,
K. N. Andersen,
L. Shari
and
Z.-C. Fan. From monoclonal antibodies to small peptides and mimetics: size reduction of the binding site in the immunoglobulin superfamily, L. Zema, G. Cotsarelis and M. I. Greene. Synthesis and assembly of antibodies in natural and artificial environments. R. Sitia and A. Cattaneo. Genetic manipulations of antibodies. From variable domains to constant regions. V. Ghetie and E. S. Ward. Engineering and phage display of antibody fragments and minibody repertoires. M. Sellazzo. F. Martin. S. Venturini, G. Esposito and C. Traboni (each chapter contains references) Index.
Gene Probes B. D. Hames
University
1. A Practical Approach and S. J. Higgins (MS). IRL Press at Oxford Press. Price f27.50 Paperback, ISBN
0199634009. Gene Probes I and its sister volume, Gene Probes 2 together constitute the second edition of the 1985 publication, Nucleic Acid Hybridisation A Practical Approach. However, because of the recent explosion of practical technologies in this area the books are not simply updates, but major revisions and expansions of the original coverage, designed to reflect the major impact of DNA and RNA isolation, and oligonucleotide and antibody probes on molecular genetic research today. Gebe Probes 1 concentrates on the synthesis of gene probes and methods of labelling them, while Gene Probes 2 covers the application of these probes in analysis of gene