The past decade has been a period of explosion of knowledge on the chemistry and pharmacology of snake toxins. Thanks to the development of protein chemistry, nearly a hundred snake toxins have been purified and sequenced, representing one of the largest families of sequenced proteins. Moreover, the mode of action of these toxins has been largely elucidated by the concerted efforts of pharmacologists, electro physiologists, and biochemists. As a result of these studies, some of the snake toxins, e.g., a-bungarotoxin and cobra neurotoxins, have been extensively used as specific markers in the study of the acetylcholine receptors. Indeed, without the discovery of these snake toxins, our knowledge of the structure and function of nicotinic acetylcholine receptors would not have advanced so rapidly. The contribution of snake venom research to the biomedical sciences is not limited to the study of cholinergic receptors. Being one of the most concentrated enzyme sources in nature, snake venoms are also valuable tools in biochemical research. Venom phosphodiesterase, for example, has been widely used for structural studies of nucleic acids; proteinase, for the sequence studies of proteins and pep tides ; phospholipase A , for lipid research; and L-amino acid oxidase for identifying optical z isomers of amino acids. Furthermore, snake venoms have proven to be useful agents for clarifying some basic concepts on blood coagulation and some venom enzymes, e.g., thrombin-like enzymes and pro coagulants have been used as therapeutic agents.

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I: History, Ecological and Zoological Aspects.- 1 History of Snake Venom Research.- References.- 2 Classification and Distribution of Venomous Snakes in the World.- References.- 3 The Venom Glands of Snakes and Venom Secretion.- A. Introduction.- B. General Morphology and Histology.- I. Venom Glands of Elapidae.- II. Venom Glands of Viperidae.- C. The Fine Structure of the Secretory Cell During the Venom Regeneration Cycle.- D. Intracellular Transport of Venom Proteins.- E. Venom Synthesis and Secretion.- I. The Venom Regeneration Cycle.- II. Synthesis and Secretion of Different Venom Components.- III. Total Venom Yield and the Amount of Venom Expelled During the Bite.- F. Concluding Remarks.- References.- II: Chemistry and Biochemistry of Snake Venoms.- 4 Enzymes in Snake Venom.- A. Introduction.- B. Distribution of Enzymes in Snake Venoms.- C. Methods for Purification, Isolation, and Crystallization of Snake Venom Enzymes.- I. Polyacrylamide Gel Electrophoresis.- II. Isoelectric Focusing.- III. Molecular-Sieve Chromatography.- IV. Ion-Exchange Chromatography.- D. Biochemical Properties of Snake Venom Enzymes.- I. Oxidoreductases.- 1. L-Amino Acid Oxidase.- 2. Lactate Dehydrogenase.- II. Enzymes Acting on Phosphate Esters.- 1. Endonuclease.- 2. Phosphodiesterase.- 3. 5?-Nucleotidase.- 4. Nonspecific Phosphomonoesterase.- 5. "Paraoxonase" (O,O-Diethyl O-p-Nitrophenyl Phosphate, O-p-Nitrophenyl Hydrolase).- III. Enzymes Acting on Glycosyl Compounds.- 1. Hyaluronidase.- 2. Heparinase-like Enzyme.- 3. NAD Nucleosidase.- IV. Enzymes Acting on Peptide Bonds.- 1. Endopeptidases.- 2. Peptidases.- 3. Arginine Ester Hydrolases.- 4. Kininogenase.- V. Enzymes Acting on Carboxylic Ester Bonds.- 1. Phospholipase A2.- 2. Phospholipase B and Phospholipase C.- 3. Acetylcholinesterase.- VI. Enzyme Acting on Arylamides.- E. Summary.- References.- 5 Chemistry of Protein Toxins in Snake Venoms.- A. Introduction.- B. Toxins with Postsynaptic Neurotoxin-Membrane Toxin Structure.- I. Curaremimetic Toxins.- 1. Introduction.- 2. Isolation of Curaremimetic Toxins.- 3. Characteristics of Curaremimetic Toxins.- 4. Interaction with the Acetylcholine Receptor.- 5. Structural Information.- 6. Chemical Modifications.- a) Amino Groups.- b) Arginine Residues.- c) Carboxyl Groups.- d) Tryptophan.- e) Tyrosine.- f) Disulfide Bridges.- g) Histidine.- h) Modifications Involving a Large Increase in Size.- 7. Discussion.- II. Membrane Toxins.- 1. Introduction.- 2. Mode of Action.- 3. Structural Information.- 4. Chemical Modifications.- C. Toxins with Phospholipase Structure.- I. Notexin and its Homologues.- II. Taipoxin.- III. Crotoxin.- IV. ?-Bungarotoxin.- V. Enhydrina schistosa Myonecrotic Toxins.- VI. Some Other Toxic Phospholipases A.- VII. Pharmacologic and Biochemical Effects.- 1. Presynaptic Neurotoxicity.- 2. Inhibition of High Affinity Choline Uptake.- 3. Postsynaptic Effects and Myotoxicity.- 4. Antagonism by High Mg2+, Ca2+, and Low Ca2+.- VIII. Phospholipase A Activity and Presynaptic Neurotoxicity.- IX. Concluding Remarks.- D. Other Toxins.- I. Crotamine.- II. Convulxin and Gyroxin.- III. Mojave Toxin.- IV. Other Crotalid Toxins.- V. Viperotoxin.- VI. Toxins from Bungarus caeruleus Venom.- 1. Ceruleotoxin.- 2. Post- and Presynaptic Neurotoxins.- E. Conclusion.- References.- 6 The Three-Dimensional Structure of Postsynaptic Snake Neurotoxins: Consideration of Structure and Function.- A. Introduction.- B. The Postsynaptic Neurotoxins: Survey of Three-Dimensional Prototype Structure; Deviant Toxins, Chemical Modification Studies. Preliminary Review.- I. Primary Sequence of Erabutoxin b.- II. Three-Dimensional Structure of Erabutoxin b.- 1. Molecular Size and Shape.- 2. Backbone Chain Conformation in the Erabutoxin Molecule.- III. Residue Sequences: Invariant and Conservative Substitutions in the Long and Short Chain Series of Neurotoxins.- IV. Chemistry and Chemical Modification Studies.- 1. Residues not Subject to Study by Group-Specific Reagents.- a) Serine-Threonine.- b) Glycine.- c) Proline.- d) Asparagine.- e) Alanine, Leucine, Isoleucine, and Valine.- 2. Invariant and Conservatively Substituted Residues as Studied by Chemical Modification.- a) Disulfide Linkages.- b) Tyrosine.- c) Tryptophan.- d) Aspartic Acid, Glutamic Acid.- e) Arginine.- f) Amino Groups.- 3. Toxin Modification by Deletion or by Size Increase.- a) Carboxyl-Terminal Deletion of a Long Chain Toxin.- b) Polymerization.- 4. Summary.- V. Physicochemical Studies of Neurotoxins and Their Derivatives.- 1. Spectroscopic Studies of Native Toxin Conformation in Aqueous and Aqueous-Organic olvent.- a) Optical Rotatory Dispersion (ORD) and Circular Dichroism (CD) Spectra.- b) Laser-Raman Spectra.- 2. Spectroscopic Studies of Chemically Modified and/or Denatured Neurotoxins.- a) Disulfide Linkages.- b) Tyrosine.- c) Tryptophan.- VI. Theoretical and Model Studies of Neurotoxin Conformation and Three-Dimensional Structure.- 1. Prediction of Conformation in the Neurotoxins.- a) ? Helix.- b) ? Pleated Sheet.- c) ? Turns.- 2. Predictions of Three-Dimensional Structure in the Neurotoxin Series.- a) Model Structure Studies.- b) Energy Minimization Studies.- c) Theoretical Chemical Models.- VII. X-ray Crystal Structure Studies of Other Neurotoxins.- 1. Erabutoxin a (Asn 26 Erabutoxin b).- 2. Neurotoxin b from Laticauda semifasciata (Philippines).- 3. Erabutoxin c.- 4. Laticotoxin a and Cobrotoxin.- C. Structure-Function Relationship in the Postsynaptic Neurotoxins. The Three-Dimensional Structure of Erabutoxin b as Prototype in both Long and Short Toxins.- I. Erabutoxin b and the Short Toxins: The Reactive Site.- II. Erabutoxin b and the Short Toxins: Nonreactive Site Regions.- III. Erabutoxin and the Long Toxins: Reactive Site.- IV. Erabutoxin and the Long Toxins: Nonreactive Site Regions.- V. Long and Short Toxins: Biochemical and Biological Differences.- VI. Erabutoxin b and the Short Toxin Series: Detailed Intramolecular Packing.- 1. ? Pleated Sheet and ? Turns.- 2. Intramolecular Interactions: Particularly Those Involving Invariant and Type-Conserved Residues.- a) Main Chain-Main Chain and Main Chain-Side Chain Hydrogen Bonds.- b) Side Chain-Side Chain Interactions.- D. Conclusions.- I. The Present View.- 1. Structure: General.- 2. Comparison of Short and Long Toxins.- 3. Structural and Functional Residues.- a) Structural Residues.- b) Functional Groupings.- c) Residues of …