Frank Vella, M.D., Ph.D., M.A., D.Sc.(Honorary)

Since 1971, Dr. Vella has been Professor of Biochemistry at the University of Saskatchewan, Canada. He received his early training in Malta and is a former Rhodes School. He is a recognized pioneer in the study of hemoglobinopathies, thalassemias, and erythrocyte enzymopathies. Professor Vella has received teaching awards from his University and is recognized as an outstanding speaker on educational approaches in biochemistry. As Chairman of the Committee on Education of the International Union of Biochemistry and Molecular Biology from 1982 to 1991, he organized and directed Workshops in twenty countries around the world. Dr. Vella has had a major impact on the development of biochemical education in many developing countries.

These are very exciting times for biochemistry and especially for that part that pertains to human biology and human medicine. The much discussed Human Genome Project is likely to be completed very early in the next millennium, by the time most users of Textbook of Biochemistry With Clinical Correlations have graduated. The Human Genome Project should provide a blueprint of the 100,000 or so genes that the human genome is estimated to contain and lead to an explosion of amazing proportions in knowledge on complex physiological processes and multigenic disorders. This mapping will reveal undreamed of interrelationships and elucidate control mechanisms of the fundamental processes of development of the human organism and of their interactions with both milieus (the internal and external). Already, one eukaryotic genome (that of brewer’s yeast, comprising 14 million base pairs in 16 chromosomes) was completed just before I set out to write this Foreword, while three microbial genomes (that of Mycoplasma genitalium- 580,070 base pairs; - Hemophilus influenzae- 1.83 million base pairs; and Synechosystis- a photosynthetic organism- 3.57 million base pairs) have been completed within 3 to 18 months of isolation of their DNA. Work on the genomes of Mycobacterium tuberculosis (4.5 million base pairs) and of Plasmodium falciparum- the malarial parasite (27 million base pairs in 14 chromosomes)- is now being undertaken, and should lead to knowledge that can produce novel approaches to the treatment and control of these two scourges of humankind. The theoretical and technical principles involved in this type of work are clearly described in chapters 14, 15 and 18 of Textbook of Biochemistry With Clinical Correlations which will ensure that readers will understand and appreciate future developments in the field.

Discoveries on the molecular basis of human disease are also being reported at an unprecedented and dizzying rate, opening wider and wider the window to many less frequent afflictions produced by mutated genes accumulating in the human gene pool. The era of molecular medicine has already arrived. Since the very first edition of Textbook of Biochemistry With Clinical Correlations, the correlations have been a feature that has made the book truly unique. In this new edition of the book, the correlations are numerous, succinct and integrated with , but also independent of, the text. They not only reflect current progress but indicate more than ever before, how Biochemistry, Molecular Biology and Human Genetics have become the foundation stones of all areas of modern Medicine. These previously separate disciplines have become so intimately and inextricably intertwined that little knowledge and understanding of one can occur without knowledge and understanding of others. One of the many strengths of this book is that clear examples of the convergence and integration of biological disciplines can be found in the clinical correlations.

In this fourth edition of Textbook of Biochemistry With Clinical Correlations, the contributors have provided an up-to-date, and logical coverage of basic biochemistry, molecular biology, and normal and abnormal aspects of physiological chemistry. This material is very appropriate and relevant for medical and other health science students, particularly as we approach the third millennium in the midst of amazing and pervasive progress in medical science and biotechnology. To enhance the text, a completely new series of vivid illustrations has been added, which will undoubtedly further the readers’ understanding of the complexity of many of the concepts. Students of medical and health sciences should appreciate that the time and effort invested in learning the material presented in Textbook of Biochemistry With Clinical Correlations, will be very well spent. This knowledge will provide the framework within which further developments will be understood and applied as the readers begin to care for the physical and mental well-being of those entrusted to them. Furthermore, the knowledge derived from this book will also provide satisfying insight into the processes that underlie human life and the amazing power of the human mind to explore and understand it. As in previous editions, the fourth edition includes many multiple choice questions (and answers) at the end of each chapter that should facilitate this learning while ensuring success in professional and other examinations.

I am happy and privileged to have watched the growth of human biochemistry (because of my teaching and research responsibilities) since my medical student days nearly half-a-century ago. It has been an amazing spectacle, full of thrills and exciting adventures into aspects of human cells that were previously shrouded in mystery and ignorance. As my knowledge has increased so has my sense of awe and wonder at the unfolding beauty of this marvelous display of nature’s secrets.

As the late Alberto Sols frequently said: "The Biochemistry of today is the Medicine of tomorrow". Textbook of Biochemistry With Clinical Correlations illustrates the veracity of this insight.

The continued rapid advances in knowledge, particularly due to the techniques of molecular biology, required a critical review and evaluation of the entire content of the previous edition. Every chapter has been revised and updated. Significant additions of new material, clarifications, and some deletions were made throughout. Amino acid metabolism was combined into a single chapter and DNA structure and function was divided into two chapters for better coverage of this rapidly expanding field. Topics for inclusion were selected to cover the essential areas of both biochemistry and physiological chemistry for upper-level undergraduate, graduate-level and especially professional school courses in biochemistry. Since the application of biochemistry is so important to human medicine, the text has an overriding emphasis on the biochemistry of mammalian cells.

The textbook is written such that any sequence considered most appropriate by an instructor can be presented. It is not formally divided into major sections, but related topics are grouped together. After an introductory chapter on cell structure, chapters two to five concern the Major Structural Components of Cells, that is proteins and their many functions, and cell membranes and their major roles. Metabolism is discussed in the following eight chapters, starting with the conservation of energy, then the synthesis and degradation of the major cellular components, and concluding with a chapter on the integration of these pathways in humans. The next section of six chapters covers Information Transfer and Its Control, describing the structure and synthesis of the major cellular macromolecules, that is DNA, RNA, and protein. A separate chapter on Biotechnology is included because information from this area has had such a significant impact on the development of our current state of biochemical knowledge. The section concludes with a chapter on the Regulation of Gene Expression, in which mechanisms in both prokaryotes and eukaryotes are presented. The fourth major section represents Signal Transduction and Amplification and includes two chapters on hormones that emphasize their biochemical functions as messengers and a chapter on Molecular Cell Biology describes four major mammalian signal transducing systems. The textbook concludes with six chapters on topics that comprise Physiological Chemistry, including cytochrome P450 enzymes and xenobiotic metabolism, iron and heme metabolism, gas transport and pH regulation, digestion and absorption, and human nutrition.

A major addition from previous editions is the extensive use of color in the illustrations as a means to emphasize important points. All figures were reviewed and new drawings were prepared to illustrate the narrative discussion. In many cases the adage ``A picture is worth a thousand words'' is appropriate and the reader is encouraged to study the illustrations because they are meant to illuminate often confusing aspects of a topic.

In each chapter the relevancy of the topic to human life processes are presented in Clinical Correlations, which describe the aberrant biochemistry of disease states. A number of new Correlations have been included. The Correlations are not intended to review all of the major diseases but rather to cite examples of disease processes where the biochemical implications are well established. In addition we specifically avoided presenting clinical case reports because it was considered more significant to deal with the general clinical condition. References are included to facilitate exploration of the topic in more detail. In some cases similar clinical problems are presented in different chapters, but each from a different perspective. All pertinent biochemical information is presented in the main text, and an understanding of the material does not require a reading of the Correlations. In a few cases, clinical discussions are part of the principal text because of the close relationship of some topics to medical conditions.

Each chapter concludes with a set of Questions and Answers; the multiple-choice format was retained as being valuable to students for self-assessment of their knowledge. The question type was limited to the types now occurring in national examinations. All questions were reviewed and many new ones added. The questions cover a range of topics in each chapter, and each has an annotated answer, with references to the page in the textbook covering the content of the question. The appendix, Review of Organic Chemistry, is designed as a ready reference for the nomenclature and structures of organic molecules encountered in biochemistry and is not intended as a comprehensive review of organic chemistry. The material is presented in the Appendix rather than at the beginning of those chapters dealing with the metabolism of each class of organic molecules. The reader might find it valuable to become familiar with the content and then use the Appendix as a ready reference when reading related sections in the main text.

We still believe that a multicontributor textbook is the best approach to achieve an accurate and current presentation of biochemistry. Each author is involved actively in teaching biochemistry in a medical or graduate school and has an active research interest in the field in which he or she has written. Thus, each has the perspective of the classroom instructor, with the experience to select the topics and determine the emphasis required for students in a course of biochemistry. Every contributor, however, brings to the book an individual approach, leading to some differences in presentation. However, every chapter was critically edited and revised in order to have a consistent writing style and to eliminate repetitions and redundancies. A limited repetition of some topics in different chapters was permitted when it was considered that the repetition would facilitate the learning process.

The individual contributors were requested to prepare their chapters for a teaching book. The book is not intended as a compendium of biochemical facts or a review of the current literature, but each chapter contains sufficient detail on the subject to make it useful as a resource. Each contributor was requested not to refer to specific researchers; our apologies to those many biochemists who rightfully should be acknowledged for their outstanding research contributions to the field of biochemistry. Each chapter contains a Bibliography that can be used as an entry point to the research literature.

In any project one person must accept the responsibility for the final product. The decisions concerning the selection of topics and format, reviewing the drafts, and responsibility for the final checking of the book were entirely mine. I welcome comments, criticisms, and suggestions from the students, faculty, and professionals who use this textbook. It is our hope that this work will be of value to those embarking on the exciting experience of learning biochemistry for the first time and to those who are returning to a topic in which the information is expanding so rapidly.

Thomas M. Devlin