Human Cholinesterases and Anticholinesterases

Preface Chapter 1 Biochemical and Biological Background 1 Overview of Cholinesterases 1.1 Nomenclature, Definition, and History 1.2 Cholinesterases as Elements in Cholinergic Transmission 1.3 Catalysis by Cholinesterases as Related to the Unique Properties of Their Three-Dimensional Structure 2 Biochemically Defined Subsites and Their Roles in Hydrolysis Activity 2.1 Esteratic Site 2.2 Presumptive Active-Center Anionic Site 2.3 Hydrophobie Site 2.4 Peripheral Anionic Site 2.5 Acetylcholine Binding to the Peripheral Site 2.6 Peripheral Organophosphorus Site 3 Anticholinesterases 3.1 Naturally Occurring Inhibitors 3.2 Synthetic Cholinesterase Inhibitors in Medicine 3.3 Anticholinesterase Organophosphorous Nerve Gases and Insecticides 3.4 Cholinesterase Domains Involved in Carbamate Toxicity 4 Cell Type and Subcellular Localization of Cholinesterases 4.1 Embryonic Origins of Cholinesterase Subtypes 4.2 Tissue Specificity and Developmental Alterations 4.3 Soluble Cholinesterases in Body Fluids 4.4 Cholinesterase Modulations in Cultured Cells 4.5 Control of Cholinesterase Production in Muscle 5 Molecular Polymorphism and Its Genomic Origin 5.1 General Polymorphic Scheme 5.2 Biochemical Approaches to the Complexity of Cholinesterase Polymorphism 5.3 Genetic Basis of Polymorphism 6 Putative Biological Roles of Cholinesterases 6.1 Nervous System Involvement 6.2 Implications for Motility 6.3 Development and Growth 6.4 Role of Butyrylcholinestrase Compared with That of Acetylcholinesterase 6.5 Suggestions for Peptidase Activity of Cholinesterases 7 Evolutionary Divergence and Conservation of Cholinesterases 7.1 At the Nucleotide Level 7.2 At the Primary Amino Acid Sequence Level 7.3 At the Level of Putative Biological Function 8 Genetic Variants of Human Cholinesterases 8.1 Electrophoretic Characterization of Butyrylcholinesterase Variants 9 Cholinesterases and Disease States 9.1 Nervous System Disorders 9.2 Hématologie Disorders 9.3 Proliferative Blood Cell Disorders 9.4 Autoimmune Diseases 9.5 Reproductive System Malfunction and Ovarian Adenocarcinomas 9.6 Postanesthetic Apnea 9.7 Organophosphorus Intoxication 9.8 Other Diseases Chapter 2 Human Cholinesterase Genes and Their Expression 1 Molecular Cloning and Expression of Human Cholinesterase Coding Sequences 1.1 Human Acetylcholinesterase and Butyrylcholinesterase cDNAs Differ in Their Basic Properties 1.2 Molecular Cloning of the Human Acetylcholinesterase Coding Sequence and Its Expression 1.3 Comparative Analysis of Acetylcholinesterase and Butyrylcholinesterase Coding Sequences 1.4 Expression of the Butyrylcholinesterase Gene in Chorionic Villi 1.5 Preferential Transcription of Acetylcholinesterase over Butyrylcholinesterase mRNAs in Fetal Human Cholinergic Neurons 1.6 Coordinated Expression of Cholinesterase Genes in Developing Human Germ Cells 2 Promoter Elements and Alternative Splicing in the Human Acetylcholinesterase Gene 2.1 Human Acetylcholinesterase Promoter Includes Clustered Binding Sites for Multiple Transcription Factors 2.2 Variable Choices for Carboxyl Termini 2.3 Alternative Splicing Creates Two Distinct Acetylcholinesterase Forms 2.4 Energy and Stability Considerations for Acetylcholinesterase 2.5 Nucleotide Composition and Potential Methylation Sites 2.6 Variable Acetylcholinesterase Forms 2.