| HOW THIS BOOK TELLS THE STORY OF BIOCHEMISTRY
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| The main pathways of carbohydrate and lipid metabolism are routes of access to other processes in biochemistry
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| Therefore we start with an introduction to the structure and function of proteins, lipids, and biological membranes. Figure 1.1 is a simplified flow chart giving an overview of human biochemistry. Proteins are the building-blocks and catalysts of biochemical systems: as structural units, they form the architectural framework of our tissues; as enzymes, together with helper molecules known as coenzymes and cofactors, they catalyze and control biochemical reactions. We describe the elements of the homeostatic environment in which human metabolism takes place, such as pH, oxygen tension, inorganic ion and buffer concentrations. This is important to understand, because treatments which aim to maintain the stability of this environment are a significant part of clinical medicine. The chapter on blood is particularly important, because plasma is an accessible 'window' on metabolism and serves as a source of clinical information for the diagnosis and management of disease. On the other hand, the enzymatic reactions involved in blood coagulation, and the complexity of the immune system, illustrate the sophistication of our defenses against disturbances in this environment.
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| Figure 1.1 Flow chart of human biochemistry. Throughout this book we will be discussing interrelationships between nutrients, energy metabolism and structure of cells and organs. We will highlight the role of catalytic and regulatory molecules and the control of cell cycle and metabolism by the information encrypted in the nucleic acids. |
| Biological membranes compartmentalize metabolic processes and process signals which control them
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| Biological membranes perform important roles in the compartmentalization of metabolites and metabolic pathways. Linked with this role is their fundamental function in metabolite transport, and also their role in receiving signals from other cells and organs. We discuss the structure of membranes both in the separation of different subcellular spaces and in the transport of ions, metabolites and larger biomolecules. Note that most of the body's energy is consumed in the maintenance of ion charge and metabolite gradients across biological membranes.
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Energy released from nutrients is distributed throughout the cell in the form of adenosine triphosphate
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| We introduce bioenergetics, the science of energy recovery and utilization in biological systems, through the function of mitochondrial membranes in oxidative phosphorylation. This is the process involving oxygen consumption, or respiration, by which we capture the energy of fuels, produce a hydrogen ion gradient, and convert this energy to adenosine triphosphate (ATP). The molecules of ATP are the 'common currency of metabolism' for exchange of metabolic energy: they transduce the energy from fuel metabolism for use in work, transport, and biosynthesis.
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| Glucose is a key molecule in fuel metabolism
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| We introduce fuel metabolism by describing the digestion and absorption of nutrients in the gut, followed by discussion of our nutritional requirements for both main nutrients (proteins, carbohydrates, fats, and minerals) and the micronutrients - vitamins and trace elements. We also discuss the role of diet in health and disease.
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| The metabolism of fuels is introduced through glycolysis, an ancient, universal anaerobic metabolic pathway for glucose metabolism and energy production. Glycolysis proceeds through identical steps both in our brain cells and in the anaerobic bacteria in our intestines; it transforms glucose to pyruvate, setting the stage for oxidative metabolism in the mitochondrion. This pathway provides an opportunity to introduce the mechanisms of regulation of metabolic pathways by small-molecule allosteric effectors, by reversible chemical modification of key enzymes, and by control of gene expression.
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| Glucose is not only our major carbohydrate fuel, but also a stringently regulated circulating form of carbohydrate in blood. The maintenance of a normal concentration of blood glucose, only one-fifth of a teaspoon of sugar in a liter of blood (100 mg/dL; 1 g/L; 5 mmol/L) is essential for our survival. When blood glucose decreases to less than 45 mg/dL (2.5 mmol/L), we may fall into a hypoglycemic coma; when it remains consistently greater than 125 mg/dL (7 mmol/L), we are diabetic and are at risk for renal, vascular, and eye
disease. Several chapters in this book explain different aspects of glucose metabolism. We also discuss the metabolism of glycogen, the storage form of glucose in liver and muscle. While talking about glycogen, we introduce the role of hormones in the regulation of metabolic pathways, and describe how organs use hormones to communicate with one another, and how hormones activate, inactivate, and coordinate metabolic activities within and among cells and organs.
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| Oxygen is essential for metabolism but the body needs to protect itself against its excess
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| Although oxygen is not required for conversion of glucose to lactate during glycolysis, it is needed for oxidative metabolism of pyruvate to carbon dioxide and water - a process that is essential for maximal extraction of the energy available from glucose. However, oxygen can also be toxic, causing oxidative stress and widespread tissue damage. We discuss both the advantageous and disadvantageous features of oxygen, emphasizing how we harness it usefully and, at the same time, protect ourselves from its more damaging effects through antioxidant defenses.
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| In aerobically-operating cells, pyruvate is transformed into another key metabolite, acetyl coenzyme A (acetyl-CoA), which is the common intermediate in the energy metabolism of carbohydrates, lipids, and amino acids. Acetyl-CoA enters the central metabolic engine of the cell, the tricarboxylic acid cycle (TCA cycle, also known as citric acid cycle or Krebs cycle) in the mitochondrial matrix. The TCA cycle oxidizes acetyl CoA to carbon dioxide and reduces the important coenzymes, nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD). These reduced nucleotides capture the energy from fuel oxidation and are the substrates for the final pathway: oxidative phosphorylation in the mitochondrion. Their oxidation provides the energy for synthesis of ATP.
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| Eating and fasting shift body metabolism between the anabolic and catabolic states
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| The fed and fasting states represent two entirely different patterns of metabolism - anabolism and catabolism. As you work your way through energy metabolism, a complex web of interactions between biochemical pathways will become evident. The process of glycolysis, in addition to its role in setting the stage for energy metabolism, produces metabolites that are the starting point for synthesis of amino acids, proteins, lipids, and nucleic acids.
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| An important principle that evolves is the partial reversibility of the main pathways of carbohydrate and lipid metabolism - catabolism versus anabolism, in response to food intake. The direction of metabolism is constantly shifting during the feed-fast cycle. In the fed state, the active pathways are glycolysis, glycogen synthesis, lipogenesis, and protein synthesis, rejuvenating tissues and storing the excess of metabolic fuel. In the fasting state, which begins only a few
hours after our last meal, the direction of metabolism is reversed: glycogen and lipid stores are degraded, protein is converted into glucose by the pathway of gluconeogenesis, and other biosynthetic processes are slowed down. We placed particular emphasis on explaining the mechanisms for adaptation to the changes in energy status induced by feeding, fasting, changing diets and starvation. We also consider the integration of fuel metabolism within and among tissues, storage of fuel in tissues and its transport in plasma, fuel preferences of individual tissues, and the derangements in fuel metabolism that occur in diabetes and atherosclerosis.
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| Tissues perform specialized metabolic functions
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| To illustrate the diversity of biochemistry in specialized tissues, we describe the mechanism of muscle contraction, the roles of the lung and kidneys in acid-base and electrolyte balance, that of the liver in biosynthesis and detoxification, and the processes of bone metabolism and biological mineralization. We then focus on the role of specialized microstructures, such as glycoconjugates (glycoproteins, glycolipids, and proteoglycans) and their role in cell-cell interactions and in the extracellular matrix.
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| The genome and cellular signaling underlie it all
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| We then turn your attention to the structure of the genome, the mechanism of conservation and transfer of genetic information, the control of protein synthesis, and the regulation of gene expression. These pathways are complex - protein synthesis is controlled by information encoded in deoxyribonucleic acid (DNA) and transcribed into ribonucleic acid (RNA), which is then translated into peptides that fold into functional protein molecules. Not only is the spectrum of expressed proteins important, but also the control of their temporal expression during development, adaptation, and aging. Information presented in these chapters offers many opportunities for understanding the therapies and strategies for fighting bacterial and viral infections. This is followed by a discussion of applications of recombinant DNA and polymerase chain reaction (PCR) technology in the clinical laboratories and in molecular medicine. The remaining chapters of the book deal with integrated topics, such as the function of the immune system, biochemical endocrinology, and the specialized biochemistry of nerve tissue. In separate chapters we deal with the issues of cell growth, the decline of biochemical systems during aging, the failure of biochemical controls in cancer, and the fascinating field of cell signaling systems.
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| Integrating the knowledge of metabolism with clinical medicine
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| Figure 1.2 Biochemistry: all in one. Interrelationships between biochemical pathways. This figure has been designed to give you a bird's-eye view of the field. It may help to structure your study, or revision. |
| Biochemistry is often perceived by students as excessively complicated - but then, we are the most complicated machine
on Earth - and much more! We believe that you will find biochemistry more comprehensible once you gain a mental picture of how the different parts of metabolism interact. For this purpose, we have included a general (and necessarily much simplified) scheme (Fig. 1.2) that looks not unlike the drawing of the London Underground! It is designed to help you to place a particular aspect/pathway/class of substances in the context of the whole system, as you proceed through the various chapters in the text.
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| In many places around the world, cutting-edge medical curricula emphasize integration of basic and clinical disciplines and introduce clinical contact at an early stage. Following
this way of thinking, our important goal was that the study of biochemistry should, at its every stage, help you understand aspects of clinical practice. Therefore, throughout this book, we strive to link the basic science you learn with clinical practice, in as relevant way as possible. Our clinical examples have been carefully scrutinized by experienced practicing clinicians and laboratorians, and most of them illustrate problems that hospital residents encounter in their daily work. This should make the biochemistry you learn easier to apply and, hopefully, will turn the journey through the metabolic pathways into a relevant, enjoyable, and rewarding experience.
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Dominiczak MH. Teaching and training laboratory professionals for the 21st century. Clin Chem Lab Med 1998;36:133-36.
Full article
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| Jolly B, Rees L, eds. Medical education in the millenium. Oxford: Oxford University Press; 1998;1-268.
Full article
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