Human Cholinesterases and Anticholinesterases

Human Cholinesterases and Anticholinesterases summarizes the many fundamental concepts of human cholinesterases (ChEs) and their inhibitors.
This book is divided into three chapters that represent human cholinesterase research studies from different points of view. Chapter 1 deals with the biochemical and biological background of human ChEs. This chapter also examines the molecular polymorphism, genomic origin, genetic variants, and biological roles of these enzymes. Chapter 2 provides the molecular characterization of human ChE genes and their multileveled regulation, with a special emphasis on butyrylcholinesterase. Chapter 3 discusses the scientific, ecological, and clinical implications of the studies presented in the previous chapters.
Protein scientists, engineers, and researchers will find this work invaluable.

Contenu

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
2.7 Are There Biochemical Differences between Alternative Acetylcholinesterase Subtypes?
3 Search for Molecular Origins of Butyrylcholinesterose Polymorphism by cDNA Screening, Deletion Mutagenesis, and Xenopus Oocyte Co-injection
3.1 Microinjected Oocytes as a Heterologous Expression System to Study Cholinesterase Biosynthesis
3.2 Oocytes Injected with Synthetic Butyrylcholinesterase mRNA Produce Active Butyrylcholinesterase
3.3 Molecular Form Polymorphism
3.4 Transport and Extracellular Surface Association
3.5 Evidence for a Single Transcript
3.6 Partial Deletion Constructs
4 Chromosomal Localization of Human Cholinesterase Genes
4.1 Mapping by Genetic Linkage of Butyrylcholinesterase
4.2 Physical Mapping of the Butyrylcholinesterase Gene by Blot Hybridization to Somatic Cell Hybrid Panels
4.3 Direct PCR Amplification of Genomic Acetylcholinesterase Sequences from Somatic Hybrid Cell Lines
4.4 Verification of Chromosome 7 Assignment for the Acetylcholinesterase Gene
4.5 Cholinesterase Gene Mapping by In Situ Hybridization to Mitotic Chromosomes
4.6 Rare YT2 Blood Group Is Associated with Acetylcholinesterase Polymorphism
5 Genomic Origin of Butyrylcholinesterase Variants: Multiple Point Mutations in the Butyrylcholinesterase
5.1 Correlations of "Silent," "Atypical," and Other Butyrylcholinesterase Variants with Specific Point Mutations
5.2 Characterization of an Unusual Tumor-Specific Butyrylcholinesterase cDNA
5.3 Unusual Butyrylcholinesterase cDNA Characterized by Alternative Termination and Point Mutations in the Coding Region
5.4 3'-Extended Butyrylcholinesterase cDNA Maps to Chromosome 3q26-ter
5.5 3'-Extended Tumor Butyrylcholinesterase mRNA Transcripts Are Functional
6 Structure-Function Relationships in Human Butyrylcholinesterase Variants
6.1 Biochemical Properties of the Unusual Butyrylcholinesterase Mutants
6.2 Resistance of Glycine 70 Butyrylcholinesterase Muteins to Solanidine
6.3 Inhibited Butyrylcholinesterases Carrying the Glycine 70 Mutation Resist Oxime Reactivation
6.4 Additional Nucleotide Substitutions in the Butyrylcholinesterase Gene and Their Functional Effects
6.5 Intramolecular Relationships in Cholinesterases Revealed by Heterologous Expression of Site-Directed and Natural Cholinesterase Variants
6.6 Structure-Function Studies of the Active Site of Human Cholinesterases
7 Manipulations of Butyrylcholinesterase Gene Expression Modulate Murine Megakaryocytopoiesis In Vitro
7.1 Early Indications for Involvement of Cholinergic Elements in Platelet Production
7.2 Antisense Oligonucleotide to Butyrylcholinesterase mRNA Blocks Megakaryocytopoiesis in Culture
7.3 Conditioned Medium from Butyrylcholinesterase-Producing Xenopus Oocytes Promotes Megakaryocytopoiesis
8 In Vivo Amplification of the Human Cholinesterase Genes
8.1 In Individuals Exposed to Organophosphorous Poisons
8.2 In Leukemias
8.3 In Polycythemia Vera
8.4 In Lupus Erythematosus
8.5 In Ovarian Adenocarcinomas
8.6 Tumor-Related Chromosome 3 and 7 Abnormalities May Involve the Cholinesterase
Chapter 3 Scientific and Environmental Implications
1 Human Acetylcholinesterase and Butyrylcholinesterase Genes: Comparative Analysis
1.1 Differential Codon Usage and Exon-Intron Buildup
1.2 Transcriptional Control in Developing Neurons
1.3 Coordinated Regulation in …