E-raamat: 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
2.7 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 StructureFunction 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 StructureFunction 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 Human Germ Cells
2 Expression of Recombinant Acetylcholinesterase and Butyrylcholinesterase
in Microinjected Xenopus Oocytes 2.1 Biochemical Characteristics
2.2 Post-transcriptional Regulation of Cholinesterase Heterogeneity
2.3 Immunohistochemical Detection of Nascent Cholinesterase Molecules
3 Unusual Tumor Butyrylcholinesterase mRNA Transcripts 3.1
Chromosomal Localization of the Mutated Gb5 Butyrylcholinesterase Gene
3.2 Functional Characteristics of Extended Butyrylcholinesterase mRNA
3.3 Induction of Acetylcholinesterase Expression by a 9 S Glioblastoma
mRNA Fraction 3.4 Heterozygosity of Mutated Butyrylcholinesterase
4 In Ovo Expression of Human Butyrylcholinesterase Muteins Reveals
Structure-Function Relationships 4.1 Distinct Effects of the Single
Gly 70 and Pro 425 Mutations 4.2 Synergistic Contributions to
Biochemical Changes in Doubly Mutated Butyrylcholinesterase Variants
4.3 Dissection of Chohnesterase Domains by Combining In Vivo Mutability and
Site-Directed Mutagenesis 4.4 Differential Catalytic Activities of
Butyrylcholinesterase 4.5 Heterogeneous Origins for "Silent"
Phenotype in Butyrylcholinesterase Reveal Specific Roles for Defined Peptide
Domains 5 Isolation of Mutated Butyrylcholinesterase Sequences from cDNA
Libraries and Their Detection in Genomic DNA 5.1 Does Chromosome 16
Contain a Chohnesterase Related Gene? 5.2 Acetylcholinesterase and
Butyrylcholinesterase Are Encoded by Distinct Genes 5.3 Human
Acetylcholinesterase Gene Maps to the Long Arm of Chromosome 7 5.4
Alternative Acetylcholinesterase mRNAs Are Differentially Represented in
Diseased Tissues and Cell Types 6 Putative Involvement of
Cholinesterases in Development 6.1 Evolutionary Implications
6.2 Does Mutability in the Butyrylcholinesterase Gene Reflect a Selection
Advantage? 6.3 Chorionic Villi and Germ Cells as Potential Sites
for Environmental Pressures on Chohnesterase Genes 7 Modifications in
the Human Cholinesterase Genes 7.1 Inheritable Amplification of
Defective Butyrylcholinesterase Genes in Individuals Exposed to
Organophosphorous Insecticides 7.2 Coamplification of Cholinesterase
Genes in Leukemias and Platelet Disorders 7.3 Cholinesterase Genes
and Oncogenes Amplify in Noncancerous Thrombocytopenia Associated with Lupus
Erythematosus 7.4 Cholinesterase Genes Coamplify with Oncogenes in
Hemopoietic and Ovarian Tumors 8 Pollution and Ecological Implications
8.1 Are Mutability and Amplification of Cholinesterase Genes Related?
8.2 Prospects for Therapeutic and Biotechnological Use of
Recombinant Cholinesterases 8.3 Future Directions for Human
Cholinesterase Research Bibliography Index