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BfO~YNrllE~I~ MoleclAlar aVid Cell --- BIOCHEMISTRY --. SMITH AND WOOD SPRINGER-SCIENCE+BUSINESS MEDIA, B.V. First edition 1992 © 1992 Springer Science+Business Media Dordrecht Originally published by Chapman & Hall in 1992 Typeset in 10/11 Y2pt Palatino by EJS Chemical Composition, Midsomer Norton, Bath, Avon ISBN 978-0-412-40760-4 Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the UK Copyright Designs and Patents Act, 1988, this publication may not be reproduced, stored, or transmitted, in any form or by any means, without the prior permission in writing of the publishers, or in the case of reprographic reproduction only in accordance with the terms of the licences issued by the Copyright Licensing Agency in the UK, or in accordance with the terms of licences issued by the appropriate Reproduction Rights Organization outside the UK. Enquiries concerning reproduction outside the terms stated here should be sent to the publishers at the UK address printed on thispage. The publisher makes no representation, express or implied, with regard to the accuracy of the information contained in this book and G(Imot accept any legal responsibility or liability for any errors or omissions that maybemade. British Library Cataloguing in Publication Data Biosynthesis. -(Molecular and cell biochemistry) 1. Smith, C.A. II. Wood, E.J. III. Series 574.19 ISBN 978-0-412-40760-4 Library of Congress Cataloging-in-Publication Data Biosynthesis/[editedby]C.A. SmithandE.J. Wood p. cm.-(Molecular and cell biochemistry) ISBN 978-0-412-40760-4 ISBN 978-94-011-2356-3 (eBook) DOI 10.1007/978-94-011-2356-3 1. Biosynthesis. 1. Smith, C.A. (ChrisA.) II. Wood, E.J. (EdwardJ.),1941-. III. Series. QP517.B57B56 1991 574. 19'29-dc20 91-9916 CIP Copy Editors: Sara Firman and Judith Ockenden Sub-editor: Simon Armstrong Production Controller: Marian Saville Layout Designer: Geoffrey Wadsley (after an original design by Julia Denny) Illustrators: lan Foulis and Associates Cover design: Amanda Barragry Contents Editors' foreword vii Contributors viii Preface ix Abbreviations x Greek alphabet xii 1 Basic principles of biosynthesis 1 1.1 Introduction 1 1.2 Energy 3 1.3 The importance of enzymes 6 1.4 Making small molecules 9 1.5 Building macromolecules 11 1.6 Self-assembly 20 1. 7 Overview 24 Answers to exercises 25 Questions 26 2 Photosynthesis 28 2.1 Introduction 28 2.2 Carbon fixation 29 2.3 Initial events in CO fixation in C plants 30 2 3 2.4 Ribulose-1,5-bisphosphate carboxylase (Rubisco) 36 2.5 The C pathway 43 4 2.6 Crassulacean acid metabolism (CAM) 46 2.7 Overview 48 Answers to exercises 49 Questions 49 3 Carbohydrates and gluconeogenesis 52 3.1 Introduction 52 3.2 Gluconeogenesis from lactate 53 3.3 Gluconeogenesis from amino acids 58 3.4 Gluconeogenesis from glycerol 60 3.5 Acetyl CoA cannot be converted to glucose in mammalian tissues 60 3.6 Regulation of gluconeogenesis 60 3.7 Overview 65 Answers to exercises 65 Questions 66 4 Polysaccharides 68 4.1 Introduction 68 4.2 Biosynthesis of a glycosidic bond 69 4.3 The biosynthesis of single sugar polysaccharides 74 I L Contents v 4.4 The biosynthesis of polysaccharides containing mixtures of sugars 84 4.5 The biosynthesis of polysaccharides using lipid pyrophosphoryl sugar donors 85 4.6 Overview 89 Answers to exercises 90 Questions 91 5 Nitrogen fixation: incorporation of nitrogen into amino acids 93. 5.1 Introduction 93 5.2 Nitrogen fixation 94 5.3 Nitrogenase 97 5.4 Nitrate as a source of nitrogen 104 5.5 Incorporation of ammonia into amino acids 105 5.6 Transamination 107 5.7 Regulation of incorporation of nitrogen into amino acids 107 5.8 Overview 112 Answers to exercises 112 Questions 112 6 Amino acid interconversions 114 6.1 Introduction 114 6.2 Essential and non-essential amino acids 115 6.3 The biosynthesis of alanine, aspartate, asparagine, glutamate and glutamine 118 6.4 The biosynthesis of serine 120 6.5 Interconversion of serine and glycine 120 6.6 Carriers of one-carbon units in the cell 122 6.7 S-Adenosylmethionine as a methyl donor 125 6.8 Products derived from S-adenosylmethionine 128 6.9 Amino acids derived from glutamate 131 6.10 Overview 135 Answers to exercises 135 Questions 136 7 Purines and pyrimidines 138 7.1 Introduction 138 7.2 Strategy of biosynthesis 139 7.3 Biosynthesis of nucleotides de novo 140 7.4 Biosynthesis of deoxyribonucleotides 147 7.5 Salvage pathways 149 7.6 Overview 151 Answers to exercises 151 Questions 152 8 Lipid biosynthesis 154 8.1 Introduction 154 8.2 The biosynthesis of fatty acids 154 8.3 The eicosanoids 163 8.4 The biosynthesis of triacylglycerols 166 8.5 The biosynthesis of phosphoacylglycerols 169 8.6 Lipid transport 173 8.7 The biosynthesis of sphingolipids 176 8.8 Overview 180 Answers to exercises 180 Questions 181 vi Contents / / L_- ______- ---' 9 Polyisoprenoids and porphyrins 183 9.1 Introduction 183 9.2 Polyisoprenoid biosynthesis 183 9.3 Importance of cholesterol 184 9.4 Further variations on the polyisoprenoid theme 199 9.5 Biosynthesis of porphyrins 203 9.6 Biosynthesis of chlorophyll 206 9.7 Porphyrin degradation: bile pigment formation 207 9.8 Vitamin B12 and pernicious anaemia 208 9.9 Overview 209 Answers to exercises 210 Questions 211 Answers to questions 213 Glossary 220 Index 222 I / Contents vii Editors' foreword This book is one of a series of brief fundamental texts for junior under graduates and diploma students in the biological sciences. The series, Molecular and Cell Biochemistry, covers the whole of modern biochemistry, integrating animal, plant and microbial topics. The intention is to give the series special appeal to the many students who read biochemistry for only part of their course and who are looking for an all-encompassing and stimulating approach. Although all books in the series bear a distinct family likeness, each stands on its own as an independent text. Many students, particularly those with less numerate backgrounds, find elements of their biochemistry courses daunting, and one of our principal concerns is to offer books which present the facts in a palatable style. Each chapter is prefaced by a list of learning objectives, with short summaries and revision aids at the ends of chapters. The text itself is informal, and the incorporation of marginal notes and information boxes to accompany the main text give a tutorial flavour, complementing and supporting the main narrative. The marginal notes and boxes relate facts in the text to applicable examples in everyday life, in industry, in other life sciences and in medicine, and provide a variety of other educational devices to assist, support, and reinforce learning. References are annotated to guide students towards effective and relevant additional reading. Although students must start by learning the basic vocabulary of a subject, it is more important subsequently to promote understanding and the ability to solve problems than to present the facts alone. The provision of imaginative problems, examples, short answer questions and other exercises are designed to encourage such a problem-solving attitude. A major challenge to both teacher and student is the pace at which biochemistry and molecular biology are advancing at the present time. For the teacher and textbook writer the challenge is to select, distill, highlight and exemplify, tasks which require a broad base of knowledge and indefatigable reading of the literature. For the student the challenge is not to be overwhelmed, to understand and ultimately to pass the examination! It is hoped that the present series will help by offering major aspects of biochemistry in digestible portions. This vast corpus of accumulated knowledge is essentially valueless unless it can be used. Thus these texts carry frequent, simple exercises and problems. It is expected that students will be able to test their acquisition of knowledge but also be able to use this knowledge to solve problems. We believe that only in this way can students become familiar and comfortable with their knowledge. The fact that it is useful to them will mean that it is retained, beyond the last examination, into their future careers. This series was written by lecturers in universities and polytechnics who have many years of experience in teaching, and who are also familiar with current developments through their research interests. They are, in addition, familiar with the difficulties and pressures faced by present-day students in viii Editors' foreword / / L_- ______- --1 the biological sciences area. The editors are grateful for the co-operation of all their authors in undergoing criticism and in meeting requests to re-write (and sometimes re-write again), shorten or extend what they originally wrote. They are also happy to record their grateful thanks to those many individuals who very willingly supplied illustrative material promptly and generously. These include many colleagues as well as total strangers whose response was positive and unstinting. Special thanks must go to the assessors who very carefully read the chapters and made valuable suggestions which gave rise to a more readable text. Grateful thanks are also due to the team at Chapman & Hall who saw the project through with good grace in spite, sometimes, of everything. These include Dominic Recaldin, Commissioning Editor, Jacqueline Curthoys, formerly Development Editor, Simon Armstrong, Sub-editor, and Marian Saville, Production Controller. Finally, though, it is the editors themselves who must take the responsibility for errors and omissions, and for areas where the text is still not as clear as students deserve. DR B. CATLEY Department of Biochemistry, Heriot-Watt University, Contributors Edinburgh, UK. Chapter 4. DR J.J. GAFFNEY Department of Biological Sciences, Manchester Polytechnic, Manchester, UK. Chapter 8. DR G. HARTMANN Department of Biochemistry, University of Surrey, Guildford, UK. Chapter 7. DR P.J. LARGE Department of Applied Biology, University of Hull, Hull, UK. Chapter 6. DR J.D. McGIVAN Department of Biochemistry, University of Bristol, Bristol, UK. Chapter 3. DR P.A. MILLNER Department of Biochemistry, University of Leeds, Leeds, UK. Chapter 1. DR N.M. PACKTER Department of Biochemistry, University of Leeds, Leeds, UK. Chapter 9. DR K. SNELL Department of Biochemistry, University of Surrey, Guildford, UK. Chapter 7. DR CA. SMITH Department of Biological Sciences, Manchester Polytechnic, Manchester, UK. Chapters 1 and 8. DR L. STEVENS Department of Biological and Molecular Sciences, University of Stirling, Stirling, UK. Chapter 5. DR E.J. WOOD Department of Biochemistry, University of Leeds, Leeds, UK. Chapter 1. / Contributors ix / Preface Not much more than a hundred years ago it was believed that organic compounds could be synthesized only by organisms. Although this was shown subsequently not to be the case by the explosive development of organic chemistry as a discipline and, indeed, as an industry, the ability of most organisms to synthesize all the chemical components of which they are composed remains truly astonishing. As a result of many studies carried out largely between the 1920s and the 1960s, we now have a very good map of the pathways of metabolism and the enzymic mechanisms of all biochemical cellular transformations. With the discovery of the true nature of polymeric molecules of life, the proteins, polysaccharides and nucleic acids, a second tier of understanding was added: not only do the monomer building blocks need to be biosynthesized, they also have to be put together in a particular order specified by a genetic blueprint. These processes, too, we now understand very well, although lacunae still remain in our understanding. This volume gives an account to some of the key processes in the field of biosynthesis. The opening chapter seeks to tease out the common features of biosynthetic mechanisms and the strategies employed to build macro molecules from simple units. The ensuing chapters consider the making of monomer units such as carbohydrates and nucleotides; the joining together of monomers to make polysaccharides; and the means by which useable energy is obtained and deployed in synthetic reactions. Chapter 2 looks at life's fundamental energy source, the process of photo synthesis. Pioneering research in the 1950s led to spectacular advances in our understanding of the so called 'dark reactions' of photosynthesis yet, despite unremitting studies since then, we still have only sketchy ideas about the precise mechanisms of light trapping and energy conversion. The following two chapters look at the processes by which carbohydrates and polysaccharides are synthesized from the simpler sugars manufactured by photosynthesis, and of how glucose, life's major fuel, is recycled in vertebrate systems. All life depends on the remarkable ability of a few groups of microorganisms to capture nitrogen from the air and incorporate it into organic compounds. That they can do this in aqueous solution at atmospheric pressure and a few degrees above freezing is more remarkable still. Nitrogen fixation, the subject of Chapter 5, is exciting great interest among molecular geneticists who hope to locate the genes for nitrogen fixation proteins and transfer them into plants of potential economic importance. In Chapter 6 we examine the manufacture of amino acids, the monomer units of the proteins. The details of the pathways here are well established and, although they are complex, the text seeks to stress the common means of achieving biosynthetic ends. The details of how nucleic acids and proteins are built up from nucleotides and amino acids, respectively, have been described in the first five chapters of Molecular Biology and Biotechnology. / x Preface / L_- ______- --1 Althoughthe story of these syntheses form important elements in the theme of biosynthesis, it was thought to be more appropriate to deal with them in the context of molecular biology. Chapter 7 describes in outline how the purine and pyrimidine bases of nucleic acids are formed. This book sets out to identify the broad general principles by which organisms make more of themselves. Despite the apparent bewildering array of biochemicals and the reaction pathways needed to make them, the primary purpose is to simplify the story by continually stressing common principles. If this book succeeds in helping students to distinguish the themes and variations behind the rich orchestration, it will have served its purpose. / Preface xi /