Intended primarily for researchers working with bioactive substances such as hormones, neurotransmitters, growth factors, and connective tissue makers, this book discusses the principles of degradation in major groups of bioactive materials with respect to physiology, location, and regulation. Peptidases; receptor-mediated endocytosis; organ extraction and clearance; and the degradation of specific proteins, peptides, amines, steroids, and polysaccharoides are featured. Pathophysiology and its role in diagnostics and disease are considered throughout the book, in addition to updates of recent literature and substantial new information on physiology and pathophysiology of degradation of bioactive material. No special mathematical or kinetic background is necessary to read this book because the mathematic and kinetic concepts are facilitated through the presentation of fundamental and more advanced principles. Furthermore, illustrations and tables are provided to facilitate the understanding of the dynamic aspects of degradation processes. Degradation of Bioactive Substances: Physiology and Pathophysiology is the first comprehensive work describing the degradation of bioactive material, including information not found in biochemical textbooks on internal metabolism or pharmacokinetic textbooks on drug metabolism.
Table of Contents
INTRODUCTION. KINETICS OF WHOLE-BODY AND ORGAN DEGRADATION. Introduction. Compartmental and Multicompartmental Models. Non-Compartmental Models. Whole-Body Degradation. Organ and Tissue Degradation. Conclusion. KINETICS OF ELIMINATION FROM THE BLOOD: PRINCIPLES AND PROCEDURES. Introduction. Kinetic Models in General. Regimes of Elimination. The Concept of Clearance. Special Clearance Regimes. Experimental Procedures. Methodology. Conclusion. PEPTIDASES INVOLVED IN THE METABOLISM OF BIOACTIVE PEPTIDES. Introduction. Properties of the Peptidases. How Do Peptidases Act in Concert? Organ, Tissue and Cellular Locations of Cell Surface Peptidases. Membrane Peptidases as Cluster Differentiation (CD) Antigens. Membrane Anchorage, Release and Plasma Activity of Peptidases. Physiological Roles of Membrane Peptidases. Conclusion. RECEPTOR-MEDIATED ENDOCYTOSIS AND DEGRADATION OF POLYPEPTIDE HORMONES, GROWTH FACTORS AND NEUROPEPTIDES. Perspectives. Receptors for Polypeptide Hormones, Growth Factors and Neuropeptides. Receptor-Mediated Endocytosis. Endocytosis and Degradation of Hormones, Growth Factors, Neuropeptides and Plasma Protein. DEGRADATION OF CIRCULATING RENIN AND ANGIOTENSIN. Introduction. Physiology of Renin and Angiotensin II. Metabolism of Circulating Renin. Metabolism of Circulating Angiotensin II. The Renin-Angiotensin System in Disease. Conclusion. PROCESSING AND CLEARANCE OF ATRIAL NATRIURETIC FACTORS (ANF). Introduction. Processing of ANF Prohormone. Clearance of Bioactive ANF. Conclusion. DEGRADATION OF GASTRIC PEPTIDES: METABOLISM OF THE GASTRINS. Introduction. Structure and Synthesis of the Gastrins. Degradation of the Gastrins. Conclusion. DEGRADATION OF CIRCULATING INTESTINAL PEPTIDES: METABOLISM OF SUBSTANCE P AND VASOACTIVE INTESTINAL POLYPEPTIDE. Introduction. Degradation of Substance P. Degradation of VIP. Conclusion. DEGRADATION OF GLUCAGONS. Introduction. Structure and Synthesis of Glucagon and Related Peptides. Degradation of Glucagon. Degradation of Other Glucagon-Related Peptides. Conclusion. DEGRADATION OF PANCREATIC POLYPEPTIDE-A PEPTIDE HORMONE WITH A GLOBULAR STRUCTURE IN AQUEOUS SOLUTION. Introduction. Structure. Biosynthesis. Molecular Species in Plasma. Regulation of Secretion. Pathology. Metabolic Clearance. Influence of Structure on Stability. Conclusion. DEGRADATION OF NEUROPEPTIDES. DEGRADATION OF NEUROHYPOPHYSICAL PEPTIDES. Introduction. Vasopressin. Oxytocin. Pathophysiological Comments. Conclusion. ACTIVATION AND DEGRADATION OF COMPLEMENT; PHYSIOLOGY AND PATHOPHYSIOLOGY. Introduction. Activation of the Complement System. Regulation of Complement Activation. Biological Functions of the Complement System. Biosynthesis of Complement Components. Metabolism of Complement Components. Complement Deficiencies Affecting Regulation and Degradation of Complement. Conclusion. DEGRADATION OF CIRCULATING CONNECTIVE TISSUE COMPONENTS. Introduction. Connective Tissue Components in Body Fluids. Type III Procollagen Aminoterminal Propeptides. Other Connective Tissue Related Antigens. Conclusion. CATABOLISM OF HYALURONAN. Introduction. Rate of Turnover of Hyaluronan in Tissues. Mechanism of Removal From Tissues. Turnover of Hyaluronan in Blood. Molecular Aspects on Uptake and Degradation. Turnover Under Pathological Conditions. Conclusion. DEGRADATION OF CIRCULATING CORTICAL STEROIDS. Physiological Aspects. Chemistry. Biosynthesis. Transport in Blood. Degradation. Physiopathological Aspects. Cortisol Degradation. Aldosterone Degradation. Conclusion. DEGRADATION OF ENDOGENOUS CATECHOLAMINES. Introduction. Assessment of Sympatho-Adrenal Activity. Biochemical Aspects of Metabolism. Whole-Body Norepinephrine Turnover and Spillover to Plasma. Plasma Epinephrine Clearance. Factors Influencing the Whole-Body Clearance of Norepinephrine and Epinephrine. Catecholamine Turnover in Single Organs. Pathophysiology of Catecholamine Kinetics and Clinical Application. Conclusion. INDEX.