Biological Roles of Sialic Acid

There is a startling amount of research activity concerning the role of sialic acid in mammalian cells and in the mammalian organism. One may discern in the early literature premonitions of compounds containing sialic acid, traceable by descriptions of color reactions, as far back as the turn of the century. Work spanning the 1930s to the 1950s culmi­ nated in the crystallization of sialic acid from a wide variety of biological materials. The ubiquitous nature of the sialic acids, and the biological importance of the substances in which they occur, then became generally manifest. Since then, the chemistry and metabolism of sialic acid and its occurrence, notably, but not exclusively, in the outer cell surfaces of mammalian cells and in key extracellular glycoproteins, have received great attention. The involvement of sialic acid-containing substances in tumorigenicity and in numerous metabolic and infectious pathological conditions, and in the growth, development, and integrity of mammalian cells has achieved widespread recognition. Intensive inquiry into the biological roles of sialic acid continues in a large number of research laboratories throughout the world. This book is intended to represent for the uninitiated as well as for the expert a wide and detailed overview of the current state of knowledge. Major efforts and pioneering break­ throughs have emerged from several laboratories, located on both sides of the Atlantic, of which we make no special individual mention here since they will to some extent appear in the pages that follow.

1 Chemistry and Analysis of Sialic Acid.- I. Historical Background.- II. Natural Occurrence of Sialic Acids.- III. Isolation and Purification.- IV. Chemistry of Sialic Acids.- A. Basic Structures.- B. Stereochemistry.- C. Chemical Reactions and Derivatives.- V. Synthesis.- VI. Quantification of Sialic Acids.- A. Colorimetric and Fluorometric Assays.- B. Enzymatic Assay.- C. Gas-Liquid Chromatography.- VII. References.- 2 The Natural Occurrence of Sialic Acids.- I. Introduction.- II. The Natural Occurrence of Sialic Acids.- A. Viruses.- B. Bacteria.- C. Plants.- D. Invertebrates.- E. Primitive Chordates.- F. Vertebrates.- III. Evolution of Sialic Acids.- IV. References.- 3 The Distribution of Sialic Acids Within the Eukaryotic Cell.- I. Introduction.- II. Extracellular Sialic Acids.- III. Distribution within the Cell.- A. The Plasma Membrane.- B. Endoplasmic Reticulum.- C. Mitochondria.- D. Nuclei.- E. Other Fractions.- IV. Conclusions.- V. References.- 4 Anabolic Reactions Involving Sialic Acids.- I. Introduction: Perspective and Directions.- II. Biosynthesis of the Sialic Acids.- A. Glucose to Sialic Acid.- B. Activation.- C. Regulatory Problems.- D. Other Derivatizations.- III. Biosynthesis of Polymers, Glycoproteins, Mucins, and Glycolipids Containing Sialic Acid.- A. Colominic Acid Synthesis.- B. CMP-Sialic Acid: Lactose (?-Galactosyl) Sialyltransferase.- C. CMP-Sialic Acid: Glycoprotein (?-Galactosyl) Sialyltransferases.- D. CMP-Sialic Acid: Mucin (?-N-Acetylgalactosaminyl) Sialyltransferase.- E. CMP-Sialic Acid: Ganglioside (Glycolipid) Sialyltransferases.- IV. Thoughts on Physiological Function of Sialic Acids.- V. References.- 5 Catabolism of Sialyl Compounds in Nature.- I. Introduction.- II. Pathways of Degradation.- A. Degradation of Gangliosides.- B. Degradation of Glycoproteins.- III. Cellular Mechanism of Degradation.- A. Lysosomes.- B. Uptake and Disposition of Substrates.- IV. Functional Implications.- V. Concluding Remarks.- VI. References.- 6 Disorders of Ganglioside Catabolism.- I. Introduction—The Catabolism of Gangliosides.- II. Tay-Sachs Disease (Type I GM2-Gangliosidosis).- A. Clinical Aspects.- B. Pathology.- C. Chemistry of the Storage Material.- D. Nature of the Metabolic Defect.- E. Enzymology of Type I GM2-Gangliosidosis.- F. Prenatal Diagnosis and Treatment.- III. Type II GM2-Gangliosidosis.- A. Clinical and Pathological Aspects.- B. Chemistry of the Storage Material.- C. Metabolic Defect—Diagnosis and Treatment.- IV. Other Variant Forms.- A. Type III GM2-Gangliosidosis.- B. Hexosaminidase-A-Deficient Adults.- V. Generalized Gangliosidosis (GM1-Gangliosidosis).- A. Clinical Aspects.- B. Pathology.- C. Chemistry of the Stored Material.- D. Metabolic Defect.- VI. Potentially Related Disorders.- A. Hematoside (GM3)-Gangliosidosis.- B. Animal Model Gangliosidoses.- C. In Vitro Model Studies.- VII. References.- 7 The Biological Role of Sialic Acid at the Surface of the Cell.- I. Introduction.- II. Occurrence, Forms, and Amounts of Sialic Acid Residues at the Surface of the Cell.- III. The Masking of Cell-Surface Antigens by Sialic Acid.- IV. Sialic Acid as a Receptor at Cell Surfaces.- A. Receptor for Lectins.- B. Receptor for Viruses.- C. Receptor for Mycoplasma.- D. Receptor for Hormones.- E. Receptor for Antibodies.- F. Receptor for Circulating Glycoproteins.- G. Receptor for Tetanus Toxin.- V. Sialic Acid in Normal and Malignant or Transformed Cells.- VI. Role of Sialic Acid in Cell-to-Cell Interaction.- A. Cellular Adhesion.- B. Intercellular Aggregation.- C. Agglutination.- VII. Physiological Role of Sialic Acid Residues.- A. Transport of Ions, Amino Acids, and Proteins.- B. Phagocytosis.- C. Anaphylactic Shock, Hypercapnia, and Brain Excitability.- D. Lymphocyte Stimulation.- E. Sperm Capacitation.- VIII. Conclusion.- IX. References.- 8 The Altered Metabolism of Sialic-Acid-Containing Compounds in Tumorigenic-Virus-Transformed Cells.- I. Introduction.- II. Experimental Procedures.- A. Cells and Cell Culture.- B. Isolation, Identification, and Quantification of Gangliosides.- C. Assay of Enzymes Involved in Glycolipid Metabolism.- III. Ganglioside Metabolism in Cultured Mouse Cell Lines.- A. Distribution of Gangliosides in Normal and Virally Transformed Cells.- B. Enzymatic Studies.- C. Effect of Growth and Culture Conditions on Ganglioside Metabolism.- D. Sialic-Acid-Containing Glycolipids in Transformed Cells Obtained from Other Species.- VI. Sialic Acid and Glycoproteins in Transformed Cells.- A. Sialic Acid and Sialyltransferase Activity in Transformed Cells.- B. Membrane Glycoproteins.- C. Glycopeptides of Transformed Cells.- D. Role of Sialic Acid and Sialyltransferase.- E. Comments.- V. Relationship between Viral Transformation and Altered Ganglioside Metabolism.- A. Productive Infection of Mouse Cells.- B. Ganglioside Metabolism in Flat Revertant Cell Lines.- C. Specificity of the Altered Ganglioside Metabolism.- D. Generality of the Phenomenon.- E. Transformation of Mouse Cells by RNA Tumor Viruses and Other Agents.- VI. Discussion.- A. Molecular Basis of Altered Ganglioside Metabolism.- B. Significance.- VII. Concluding Remarks.- VIII. References.- 9 Circulating Sialyl Compounds.- I. Introduction.- II. Normal Plasma Constituents.- A. Circulating Sialoenzymes.- B. Serum Sialoglobulins.- C. Sialoglycoprotein Hormones.- III. Circulating Sialoglycoproteins in Abnormal Physiological States.- A. Diabetes.- B. Inflammatory Reactions.- C. Infectious Psychoses.- D. The Effect of Steroid Hormones.- E. Liver Disease.- F. Virus Inhibition of Hemagglutination.- G. Cancer.- H. Diet.- IV. Role of Sialic Acid in Circulating Sialoglycocompounds.- V. References.- 10 Sialidases.- I. Background and Nomenclature.- II. Bacterial Sialidases.- A. Occurrence of Microbial Sialidases.- B. Organismic Characterization and Induction of Bacterial Sialidases.- C. Purification of Bacterial Sialidases.- D. Size and Properties of Bacterial Sialidases.- E. Mode of Action of Bacterial Sialidases.- F. Biological Roles for Bacterial Sialidases.- III. Viral Sialidases.- A. Morphology and Genetics of Viral Sialidases.- B. Purification of Viral Sialidases.- C. Size of Viral Sialidases.- D. Properties of Viral Sialidases.- E. Possible Biological Roles for Viral Sialidases.- IV. Experimental Use of Microbial Sialidases.- V. Mammalian Sialidases.- A. Organ Distribution of Mammalian Sialidases.- B. Subcellular Distribution of Mammalian Sialidases.- C. Purification of Mammalian Sialidases.- D. Assay of Mammalian Sialidases.- E. Physical Properties of Mammalian Sialidases.- F. Developmental Studies of Mammalian Sialidases.- G. Possible Biological Roles of Mammalian Sialidases.- H. Sialidase Activity in Cells in Tissue Culture.- VI. References.