Pharmacy E-books » Biochemistry

Proteins Structure and Function

Madjackfrost — Sat, 10 Oct 2009 07:55:00 +0000

The present text should be suitable for all introductory modes of biochemistry, molecular biology, chemistry, medicine and dentistry. This generally means the book is suitable for all undergraduates between years 1 and 3 and this book has stemmed from lectures given as parts of biochemistry courses to students of biochemistry, chemistry, medicine and dentistry in all 3 years.

Where possible each chapter is structured to increase progressively in complexity. For purely introductory courses as would occur in years 1 or 2 it is sufficient to read only the first parts, or selected sections, of each chapter. More advanced courses may require thorough reading of each chapter together with consultation of the bibliography and secondly the list of references given at the end of the book.

Overview of book chapters:

This book will address the structure and function of proteins in 12 subsequent chapters each with a definitive theme. After an initial chapter describing why one would wish to study proteins and a brief historical background the second chapter deals with the ‘building blocks’ of proteins, namely the amino acids together with their respective chemical and physical properties. No attempt is made at any point to describe the metabolism connected with these amino acids and the reader should consult general textbooks for descriptions of the synthesis and degradation of amino acids. Chapter 3 covers the assembly of amino acids into polypeptide chains and levels of organizational structure found within proteins. Almost all detailed knowledge of protein structure and function has arisen through studies of globular proteins but the presence of fibrous proteins with different structures and functional properties necessitated a separate chapter devoted to this area (Chapter 4). Within this class the best understood structures are those belonging to the collagen class of proteins, the keratins and the extended ? sheet structures such as silk fibroin. The division between globular proteins and fibrous proteins was made at a time when the only properties one could compare readily were a protein’s amino acid composition and hydrodynamic radius. It is now apparent that other proteins exist with properties intermediate between globular and fibrous proteins that do not lend themselves to simple classification. However, the ‘old’ schemes of identification retain their value and serve to emphasize differences in proteins.

Membrane proteins represent a third group with different composition and properties. Most of these proteins are poorly understood, but there have been spectacular successes from the initial low-resolution structure of bacteriorhodopsin to the highly defined structure of bacterial photosynthetic reaction centres. These advances paved the way towards structural studies of G proteins and G-protein coupled receptors, the respiratory complexes from aerobic bacteria and the structure of ATP synthetases.

Chapter 6 focuses both on experimental and computational methods of comparing proteins where in silico methods have become increasingly important as a vital tool to assist with modern protein biochemistry. Chapter 7 focuses on enzymes and by discussing basic reaction rate theories and kinetics the chapter leads to a discussion of enzyme-catalysed reactions. Enzymes catalyse reactions through a variety of mechanisms including acid–base catalysis, nucleophilic driven chemistry and transition state stabilization. These and other mechanisms are described along with the principles of regulation, active site chemistry and binding.

The involvement of proteins in the cell cycle, transcription, translation, sorting and degradation of proteins is described in Chapter 8. In 50 years we have progressed from elucidating the structure of DNA to uncovering how this information is converted into proteins. The chapter is based around the structure of two macromolecular systems: the ribosome devoted towards accurate and efficient synthesis and the proteasome designed to catalyse specific proteolysis. Chapter 9 deals with the methods of protein purification. Very often, biochemistry textbooks describe techniques without placing the technique in the correct context. As a result, in Chapter 9 author have attempted to describe equipment as well as techniques so that students may obtain a proper impression of this area.

Structural methods determine the topology or fold of proteins. With an elucidation of structure at atomic levels of resolution comes an understanding of biological function. Chapter 10 addresses this area by describing different techniques. X-ray crystallography remains at the forefront of research with new variations of the basic principle allowing faster determination of structure at improved resolution. NMR methods yield structures of comparable resolution to crystallography for small soluble proteins. In ideal situations these methods provide complete structural determination of all heavy atoms but they are complemented by other spectroscopic methods such as absorbance and fluorescence methods, mass spectrometry and infrared spectroscopy. These techniques provide important ancillary information on tertiary structure such as the helical content of the protein, the proportion and environment of aromatic residues within a protein as well as secondary structure content.

Chapter 11 describes protein folding and stability – a subject that has generated intense research interest with the recognition that disease states arise from aberrant folding or stability. The mechanism of protein folding is illustrated by in vitro and in vivo studies. Whilst the broad concepts underlying protein folding were deduced from studies of ‘model’ proteins such as ribonuclease, analysis of cell folding pathways has highlighted specialised proteins, chaperones, with a critical function to the overall process. The GroES–GroEL complex is discussed to highlight the integrated process of synthesis and folding in vivo.

The final chapter builds on the preceding 11 chapters using a restricted set of well-studied proteins (case studies) with significant impact on molecular medicine. These proteins include haemoglobin, viral proteins, p53, prions and ?1-antitrypsin. Although still a young subject area this branch of protein science will expand in the next few years and will rely on the techniques, knowledge and principles elucidated in Chapters 1–11. The examples emphasize the impact of protein science and molecular medicine on the quality of human life.

Addition material

Protein Visualization Sources

Medical Biochemistry: Human Metabolism in Health and Disease

Madjackfrost — Sat, 03 Oct 2009 22:53:00 +0000

Human metabolism is a key component of the basic science knowledge that underlies the practice of medicine and allied health professions. It is fundamental to understanding how the body adapts to physiologic stress, how defects in metabolism result in disease, and why data from the clinical chemistry laboratory are useful to diagnose disease and monitor the efficacy of treatment.

Over the more than three decades that each of the authors has been teaching biochemistry to medical students, we have found students increasingly overwhelmed with details that tend to obscure rather than elucidate principles of human metabolism.

The main aim of this book was to provide students in the health professions with a concise resource that will help them understand and appreciate the functions, constituent reactions, and regulatory aspects of the core pathways that constitute human metabolism and which are responsible for maintaining homeostasis and well-being in humans. Authors tried to accomplish this by emphasizing function, regulation, and disease processes, while minimizing discussion of reaction mechanisms and details of enzyme structure.

Each chapter is organized in a consistent manner beginning with an explanation of the main functions of the pathway under discussion. Next comes a brief accounting of the cells, tissues, and organs in which the pathway is expressed and the conditions under which the normal function of the pathway is especially important. The bulk of each chapter is devoted to the reactions that account for the function of the pathway, with emphasis on key steps in the pathway. The next section of each chapter discusses the ways in which the activity of the pathway is regulated by hormones, genetic factors, or changes in the intracellular concentration of key metabolites. Each chapter concludes with a discussion of the more common and illustrative diseases that result from defects in or derangements of regulation of the pathway.

This volume is deliberately modest in size. Instead of providing exhaustive coverage of all the reactions that human cells and tissues are capable of executing, we have chosen examples that illustrate the physiologic and pathophysiologic significance of the topic. The authors’ expectation is that each chapter will be read for comprehension rather than to provide abundant fact and detail. During their subsequent education and professional careers, the readers will undoubtedly have need for more information on many topics discussed in this book.

Marijuana Chemistry: Genetics, Processing, Potency

Madjackfrost — Mon, 16 Mar 2009 13:43:00 +0000

Marijuana Chemistry is a one-of-a-kind book that explains the various psychoactive constituents of cannabis, with full discussions of the effect of growth conditions, harvesting, and processing, and method of ingestion on potency. This new edition of the widely respected classic features 64 pages of updates based on current research and black market studies.

Basic Concepts in Biochemistry A Student’s Survival Guide

Madjackfrost — Mon, 16 Mar 2009 13:17:00 +0000

This second edition continues to innovatively review the toughest concepts in biochemistry for maximum comprehension in a short period of time. Unlike conventional texts or review books that stress memorizing facts, BASIC CONCEPTS stresses the mastering of fundamental concepts, so that the reader truly comprehends the material and feels comfortable applying it. Dr. Gilbert uses simple, jargon-free language and award-winning teaching techniques including algorithms, mnemonics and clinical examples.

Preface.
Prologue.
Chapter 1: Where to Start.
Chapter 2: Protein Structure.
Chapter 3: Membranes and Membrane Proteins.
Chapter 4: DNA-RNA Structure.
Chapter 5: Expression of Genetic Information.
Chapter 6: Recombinant-DNA Methodology.
Chapter 7:Enzyme Mechanism.
Chapter 8: EnzymeKinetics.
Chapter 9: Signal Transduction Pathways.
Chapter 10: Glycolysis and Gluconeogenesis.
Chapter 11: Glycogen Synthesis and Degradation.
Chapter 12: TCA Cycle.
Chapter 13: Fat Synthesis and Degradation.
Chapter 14: Electron Transport and Oxidative Phosphorylation.
Chapter 15: Pentose Phosphate Pathway.
Chapter 16: Amino Acid Metabolism.
Chapter 17: Integration of Energy Metabolism.
Chapter 18: UREA Cycle.
Chapter 19: Purine Metabolism.
Chapter 20: Pyrimidine Metabolism.
Chapter 21: One-Carbon Metabolism.
Chapter 22: Tracking Carbons.
Chapter 23: ph, pKa, pROBLEMS.
Chapter 24: Thermodynamics and Kinetics.
Appendix.
Glossary.
Index.

Biochemistry of Inorganic Polyphosphates

Madjackfrost — Mon, 16 Mar 2009 00:12:00 +0000

Now in a second edition, Biochemistry of Inorganic Polyphosphates fills the need for an exhaustive resource on inorganic polyphosphate metabolism. The authors describe the structure and properties of these compounds and presents a comparative analysis of the newest and traditional methods of their extraction from cells. Distribution of polyphosphates in organisms, their localization in cells and tissues is also described.

Comprehensive presentation of inorganic polyphosphate metabolism
Follows polyphosphates in cells of organisms from different stages of evolution
Presents methods for the analysis and study of polyP-dependent enzymes
Comprehensive information on genetics, metabolism and biotechnology of polyphosphates
Textbook and reference work on all aspects of polyphosphates

DNA: The Secret of Life

Madjackfrost — Mon, 09 Mar 2009 09:06:00 +0000

Who better than James Watson to lead a guided tour of DNA? When he and his English colleague, Francis Crick, discovered the double helix structure of the DNA molecule in 1953, little could they imagine that a mere 50 years later scientists would be putting the finishing touches on a map of the human genome. In this magisterial work, Watson, who won the Nobel Prize with Crick for their discovery, guides readers through the startling and rapid advances in genetic technology and what these advances will mean for our lives. Watson covers all aspects of the genome, from the layout of four simple bases on the DNA molecule through their complex construction into genes, then to the mechanisms whereby proteins produced by genes create our uniquely human characteristics-as well as the genetic mutations that can cause illnesses or inherited diseases like Duchenne muscular dystrophy and Huntington’s disease. Watson may have mellowed a little over the years since he displayed his youthful brashness in The Double Helix, but he still isn’t shy about taking on controversial subjects. He criticizes biotech corporations for patenting genes, making diagnostic medical procedures horribly expensive and damping further basic research. He notes that while China and other countries with large populations to feed have eagerly grasped the potential of genetically modified foodstuffs, America squandered $100 million on a recall of taco shells and the genetically modified corn used in them. He pleads passionately for the refinement and widespread use of prenatal genetic testing. Watson will probably provoke the most controversy with his criticism of scientists, corporations and government funding sources for their avoidance of important areas of research-notably the genetics of skin coloration-for political reasons. Every reader who wants to understand their own medical future will want to read this book. 100 color and b&w illus.

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The Biochemistry of Cell Signalling [ILLUSTRATED]

Madjackfrost — Mon, 09 Mar 2009 09:00:00 +0000

The Biochemistry of Cell Signalling deals in depth with the principles of cell signalling, concentrating on structure and mechanism. It will serve as a reliable map through the maze of cell signalling pathways and help the reader understand how malfunctions in these pathways can lead to disease. The book is divided into four parts. Part 1 describes the machinery of signal transduction starting with the properties of signals, receptors (including receptor activation), regulators, and the molecules that link receptor and regulator. The design of signalling cascades is explained by describing central signalling pathways: the Ras-regulated MAPK and PI-3 pathways; the Rho/Rac/Cdc 42 pathway controlling chemotaxis and regulating the cytoskeleton; the G protein coupled receptor cascades in response to sensory and hormonal signals; signalling by TGF-ss in morphogenesis; cytokine signalling that controls haemopoiesis. There is also a discussion of the insulin response. As phosphorylation – dephosphorylation is involved in nearly all cellular regulatory processes, Part 1 concludes with a synopsis of its role in signalling. Part 2 describes the implementation of the signalling cascades focusing on the effect on gene transcription. After a brief description of the transcriptional machinery the regulation of transcription by cytokines and growth factors in the control of cell growth and the mechanisms and sites of control are discussed in detail. The regulators discussed include Jun/Fos, NF-AT, SREBPs, and STATs. The next two chapters cover gene regulation by nuclear receptors, including both the steroid hormone receptors and non-steroid nuclear receptors e.g. the retinoic acid receptors RAR and RXR. Part 3 studies the global cellular regulatory programs for the control of cell growth and proliferation. The first chapter concerns the regulation of the cell cycle and the role of the cyclin-dependent kinases, telomerase, Ran, and cell cycle checkpoints. The next topic is the signalling pathways in apoptosis: the TNF-receptor family death receptors, caspases, and the intracellular apoptosis signals and the role of apoptosis in the lifecycle of cells. Part 3 ends with a discussion of the signal pathways involved in the immune response, focusing on the involvement of cell-cell interactions. Part 4 considers loss of regulatory control and its consequences with respect to the molecular basis of cancer. It first describes the cellular regulatory proteins that have oncogenic potential, how they can become oncogenic and cause the transformation of normal cells to cancerous cells. Next is an analysis of the loss of developmental controls, the APC protein, ss-catenin, and the Wnt pathway, that lead to mature terminally differentiated cells reverting to immature embryonic cells. The book ends with a summary of the molecular and cellular causes of cancer and an outlook for novel therapies. Throughout the text, the emphasis is on structure and mechanism and is well illustrated with 200 figures. The Biochemistry of Cell Signalling will be an invaluable companion to all graduate students studying cell signalling.

Lehninger Principles of Biochemistry

Madjackfrost — Sat, 07 Mar 2009 13:32:00 +0000

The fourth edition of Lehninger Principles of Biochemistry stays true to the vision of its predecessors while embracing the advances made in biochemical research since the previous edition. As always, the book presents the fundamentals of biochemistry through selected topics, and emphasizes the most important recent developments and applications without abandoning the classical core of the subject. The new edition has been carefully streamlined to reduce the length of the book without compromizing content. As with previous editions, it emphasizes clear prose and student friendly explanations to optimize student comprehension.It also contains a groundbreaking new treatment of metabolic regulation, up to date coverage of DNA based information technologies, many new applications and problems, and a new graphical style for enzyme reaction mechanisms, including step by step annotations that clarify the concepts and chemical logic of enzymatic reactions. Lecturer supplements include: Instructor’s Resource CD ROM with Test Bank, Printed Test Bank and a set of 150 Overhead Transparencies. For students a Study Guide and Solutions Manual is available which includes discussion questions, a self test and a Cellular Metabolic Map, as well as a Lecture Notebook containing the essential diagrams and reaction equations in the text. The textbook’s dedicated website http://www whfreeman.com/lehninger offers numerous features including PowerPoint images, animated mechanisms and living graphs.

Highlights in Bio-Organic Chemistry

Madjackfrost — Sat, 07 Mar 2009 13:22:00 +0000

This is a fascinating introduction to the topic. Spanning the spectrum of nucleic acid chemistry, carbohydrates, peptides, molecular recognition, biosynthesis and natural biosynthesis, right up to medical and biophysical chemistry, the book provides advanced students and those already working in the field with a balanced overview.

In more than 30 contributions, a new generation of recognized scientists gives an account of the latest research in such areas as

* Artificial receptors for the stabilization of ?-sheet structures
* Carbohydrate recognition by artificial receptors
* Combinatorial chemistry as a tool for the discovery of catalysts
* The interaction of NO and peroxynitrite with hemoglobin and myoglobin
* Inhibitors against human mast-cell-tryptase as a potential approach to conquering asthma
* The selectivity of DNA replication.

A readily accessible survey for everyone wishing to stay abreast of developments.