Complex Carbohydrates of Nervous Tissue

It is only relatively recently that neurochemists and neurobiologists have shown appreciable interest in the class of macromolecules now generally re­ ferred to as complex carbohydrates, although gangliosides were, of course, first identified and studied in brain. The glycosaminoglycans fell chiefly within the province of connective-tissue biochemists, and earlier informa­ tion concerning the structure and metabolism of glycoproteins was largely limited to the more accessible glycoproteins and oligosaccharides (such as those found in plasma, milk, and urine), or ones which are relatively simple to prepare in a soluble and manageable form. Techniques were later devised for the isolation and purification of tightly bound membrane glycoproteins, where initial studies concentrated mainly on the erythrocyte, for which large amounts of a single cell population are available. Because of the structural complexity of nervous tissue and the large numbers, low concentrations, and membrane-bound form of many of its complex carbohydrates, progress has occurred more slowly in this area.

1 Structure and Distribution of Gangliosides.- 1. Introduction.- 2. Structures.- 2.1. Classification.- 2.2. Ganglio Series.- 2.3. Lacto Series.- 2.4. Hematosides.- 2.5. Lipophilic Components.- 3. Distribution.- 3.1. Gross Compartmentalization in the Nervous System.- 3.2. Brain Cells.- 3.3. Brain Subcellular Fractions.- References.- 2 Biosynthesis and Metabolism of Gangliosides.- 1. Introduction: Location and Types of Gangliosides.- 2. Biosynthesis of Brain Gangliosides.- 2.1. Synthesis by Glycosyltransferases.- 2.2. Sequential Glycosylations.- 2.3. Glycosylation in Vivo.- 2.4. From Synthetic Machinery to Membrane Structure.- 3. Turnover of Brain Gangliosides.- 3.1. Turnover in Toto.- 3.2. Developmental Correlations.- 1. Catabolism of Nervous System Gangliosides.- 1.1. Lysosomal Glycohydrolases and Plasma Membrane Sialidase (Neuraminidase).- 1.2. Deficiencies in Catabolic Glycohydrolases.- 1.3. Speculations on Sialidase Resistance of GMI.- 2. Influence of Physicochemical Properties on Metabolism.- 2.1. Possibility of Self-Aggregation.- 2.2. Receptor Functions.- References.- 3 Structure and Distribution of Glycoproteins and Glycosaminoglycans.- 1. Introduction.- 2. Structure.- 2.1. Composition and Structure of Nervous Tissue Glycoproteins.- 2.2. Composition and Structure of Brain Glycosaminoglycans….- 3. Distribution.- 3.1. Glycoproteins.- 3.2. Glycosaminoglycans.- 4. Conclusions.- References.- 4 Biosynthesis of Glycoproteins.- 1. Introduction.- 2. Sugar Nucleotide: Glycoprotein Glycosyltransferases.- 2.1. TV-Acetylgalactosaminyltransferases.- 2.2. Mannosyltransferases.- 2.3. N-Acetylglucosaminyltransferases.- 2.4. Galactosyltransferases.- 2.5. N-Acetylneuraminyltransferases.- 2.6. Fucosyltransferases.- 2.7. Glucosyltransferases.- 3. Lipid-Mediated Glycosyltransferases.- 3.1. Biosynthesis and Structure of Monosaccharide and Disaccharide Derivatives of Dolichol.- 3.2. Biosynthesis and Structure of Dolichol-Linked Oligosaccharides.- 3.3. Mode of Action of Tunicamycin as a Glycoprotein Biosynthesis Inhibitor.- 3.4. Possible Regulation of the Lipid Intermediate Pathway by Modulation of the Level of the Carrier Lipid, Dolichyl Monophosphate.- 3.5. Speculation on the Function of Dolichol-Linked Oligosaccharides and the Possible Nature of the Brain Glycoproteins Glycosylated via Lipophilic Glycosyl Donors.- 4. Subcellular Site(s) of Sugar-Nucleotide- and Lipid-Mediated Glycosyltransferases.- 5. Summary and Concluding Remarks.- References.- 5 Biosynthesis of Glycosaminoglycans.- 1. Introduction.- 2. Metabolism of Glycosaminoglycans in Nervous Tissue.- 2.1. In Vivo Studies.- 2.2. Metabolism of Glycosaminoglycans in Cultured Cells.- 2.3. Metabolism of Glycosaminoglycans in Cellular and Subcellular Fractions of Brain.- 3. Biosynthesis of Nucleotide Monosaccharides and Sulfate Precursors of Nervous Tissue Glycosaminoglycans.- 3.1. Biosynthesis of Nucleotide Monosaccharides.- 3.2. Lipid-Linked Oligosaccharides: Alternative Intermediates in Glycosaminoglycan Biosynthesis?.- 3.3. Biosynthesis of 3-Phosphoadenosine 5?-Phosphosulfate.- 4. Biosynthesis of Glycosaminoglycans in Nervous Tissue.- 4.1. Biosynthesis of Chondroitin Sulfate.- 4.2. Sulfate Fixation.- 4.3. Biosynthesis of Other Glycosaminoglycans.- 5. Subcellular Distribution of Glycosyltransferases and Sulfotransferases in Nervous Tissue.- 6. Summary and Conclusions.- References.- 6 Brain Glycosidases.- 1. Introduction.- 2. Sialidase.- 3. ?-Galactosidase.- 4. ?-N-Acetylhexosaminidase.- 5. ?-L-Fucosidase.- 6. ?-Mannosidase.- 7. Enzymes That Degrade Brain Glycosaminoglycans, and Other Glycohydrolases.- 8. Biology of Glycosidases.- References.- 7 Histochemistry and Cytochemistry of Glycoproteins and Glycosaminoglycans.- 1. Introduction.- 2. Historical Background.- 2.1. Periodic Acid-Schiff.- 2.2. Iron-Based Stains.- 2.3. Phosphotungstic Acid.- 2.4. Ruthenium Red.- 2.5. Alcian Blue.- 2.6. Cationic Ferritin.- 3. Glycosaminoglycans.- 4. Glycoproteins: Lectin Cytochemistry.- 4.1. Subcellular Fractions.- 4.2. Myelin.- 4.3. Cells and Tissue.- 4.4. Smooth Membrane Cisternae.- 4.5. Developing Synapses.- 4.6. Growth Cone Region.- 4.7. Internalization into Neurons.- 4.8. Lectin Cytochemistry: Summary and Conclusions.- 5. Toxin and Antibody Cytochemistry.- 5.1. Toxin Cytochemistry.- 5.2. Antibody Cytochemistry.- 6. Summary.- References.- 8 Glycoproteins of the Synapse.- 1. Introduction.- 2. Current Status.- 2.1. Methodology.- 2.2. Studies on Intact Junctions in Synaptosomal Plasma Membranes.- 2.3. Biosynthesis and Plasticity: Biosynthesis of Synaptic Glycoproteins.- 2.4. Glycoproteins in Recognition and Development: General Considerations and Potential Leads.- 3. Outlook.- References.- 9 Surface Glycoconjugates in the Differentiating Neuron.- 1. Introduction.- 2. An Approach to the Mapping of Cell-Surface Carbohydrates.- 3. Regional and Type-Specific Lectin Receptor Content in the Plasmalemma of Growing Neurons.- 4. Dynamics of Surface Glycoconjugates during Neuritic Elongation.- 5. Concluding Remarks.- References.- 10 Histochemistry of Polyanions in Peripheral Nerve.- 1. Introduction.- 2. Histochemistry of Peripheral Nerve.- 2.1. Colloidal Iron.- 2.2. Ferric Chloride.- 2.3. Copper.- 2.4. Barium.- 2.5. Alcian Blue.- 2.6. Lanthanum.- 2.7. Ruthenium Red.- 3. Chemical Nature of Peripheral Nerve Polyanions.- 3.1. Chemical Blocking Reactions.- 3.2. Enzyme Digestion.- 3.3. Ionic Competition and Ion Exchange at the Node.- 3.4. Nodal Alcianophilia.- 3.5. Conclusions on Nodal Cytochemistry.- 4. Functional Implications.- References.- 11 Glycoproteins in Myelin and Myelin-Related Membranes.- 1. Historical Background and Introduction.- 2. Peripheral Myelin.- 2.1. Introduction.- 2.2. Chemistry.- 2.3. Localization.- 2.4. Development.- 2.5. Pathology.- 3. Central Myelin.- 3.1. Introduction and Localization.- 3.2. Development.- 3.3. Metabolism.- 3.4. Pathology.- 3.5. Chemistry.- 4. Relevance for Myelin Structure and Perspectives.- References.- 12 Axonal Transport of Complex Carbohydrates.- 1. The Phenomenon of Axonal Transport.- 2. Axonal Transport of Complex Carbohydrates.- 2.1. Transport of Glycoproteins.- 2.2. Transport of Glycosaminoglycans.- 2.3. Transport of Gangliosides.- 3. Turnover and Redistribution of Axonally Transported Molecules.- 3.1. Metabolic Turnover Rates.- 3.2. Redistribution and Effects of Local Synthesis.- 3.3. Transsynaptic Migration.- 4. Overview and Functional Considerations.- References.- 13 Regional Aspects of Neuronal Glycoprotein and Glycolipid Synthesis.- 1. Introduction.- 1.1. Advantages of Using Identified Neurons of Aplysia.- 1.2. Advantages of Direct Pressure Injection.- 2. Distribution of [3H]Glycoproteins and [3H]Glycolipids in R2 after Intrasomatic Injection of [3H]Fucose or [3H]-N-Acetylgalactosamine.- 3. Association of Individual Glycoprotein Components with Subcellular Organelles in the Cell Body.- 3.1. External Membrane.- 3.2. Vesicles.- 4. Selective Export of Newly Synthesized Glycoproteins into Axons.- 4.1. Selective Axonal Transport.- 5. Modification of Macromolecules in the Axon of R2.- 6. Afterword.- References.- 14 Complex Carbohydrates of Cultured Neuronal and Glial Cell Lines.- 1. Introduction.- 2. Glycolipid Metabolism in Neurotumor Cell Lines.- 2.1. Neuroblastomas.- 2.2. Astrocytomas.- 2.3. Oligodendrogliomas and Schwannomas.- 3. Glycoprotein Metabolism in Neurotumor Cell Lines.- 3.1. Neuroblastomas.- 3.2. Astrocytomas (Glioblastomas).- 3.3. Oligodendrogliomas and Other Glioblastoma Cell Lines: Glycoproteins Associated with Oligodendroglial Cell Differentiation.- 3.4. Uncharacterized Gliomas.- 4. Collagen Synthesis in Neurotumor Cell Lines.- 5. Glycosaminoglycan Synthesis in Neurotumor Cell Lines.- 5.1. Neuroblastomas.- 5.2. Astrocytomas.- 5.3. Oligodendrogliomas and Schwannomas.- 6. Relevance of Studies on Neurotumor Cell Lines to Whole Brain and Relationship to Studies on Individual Cell Types.- 6.1. Neurons.- 6.2. Astrocytes.- 6.3. Oligodendrocytes.- 7. Conclusions.- References.- 15 Complex Carbohydrates of Secretory Organelles.- 1. Introduction.- 2. Complex Carbohydrates of Secretory Granules and Vesicles.- 2.1. Membranes.- 2.2. Internal Matrix.- 3. Role of Complex Carbohydrates in the Assembly and Function of Secretory Organelles.- 3.1. Membrane Recognition and Biogenesis.- 3.2. Storage of Secretion Products.- References.- 16 Glycoprotein Storage Diseases and the Mucopolysaccharidoses.- 1. Introduction.- 2. Glycoproteins of Nervous Tissue.- 2.1. Acidic (Sialo)glycoproteins.- 2.2. Neutral (Manno)glycoproteins.- 2.3. Other Types.- 3. Inborn Errors of Glycoprotein Catabolism.- 3.1. Neuraminidase Deficiency.- 3.2. ?-Galactosidase Deficiency (GM1-Gangliosidoses).- 3.3. N-Acetyl-?-Glucosaminidase Deficiency (GM2-Gangliosidoses) (Sandhoff’s Disease).- 3.4. ?-Mannosidase Deficiency (Mannosidosis).- 3.5. ?-Fucosidase Deficiency (Fucosidosis).- 3.6. N-Aspartyl-?-Glucosaminidase Deficiency (Aspartylglucosaminuria).- 3.7. Other Genetic Disorders That Involve Glycoprotein Storage.- 3.8. Effect of Oligosaccharide Storage on CNS Function.- 4. Glycosaminoglycans of Nervous Tissue.- 5. Inborn Errors of Glycosaminoglycan Catabolism (the Mucopolysaccharidoses).- 5.1. ?-L-Iduronidase Deficiency (Hurler-Scheie Syndrome): Mucopolysaccharidosis I and V.- 5.2. Iduronate Sulfate Sulfatase Deficiency (Hunter’s Disease): Mucopolysaccharidosis II.- 5.3. Sulfamidase Deficiency (Sanfilippo A Syndrome): Mucopolysaccharidosis IIIa.- 5.4. N-Acetyl-?-D-Glucosaminidase Deficiency (Sanfilippo B Syndrome): Mucopolysaccharidosis IIIb.- 5.5. N-Acetylgalactosaminyl-6-Sulfate and Galactose-6-Sulfate Sulfatase Deficiency (Morquio’s Disease): Mucopolysaccharidosis IV.- 5.6. N-Acetylglucosamine-6-Sulfate Sulfatase Deficiency (Mucopolysaccharidosis VIII?).- 5.7. N-Acetylgalactosamine-4-Sulfate Sulfatase (Arylsulfatase B) Deficiency (Maroteaux-Lamy Syndrome): Mucopolysaccharidosis VI.- 5.8. ?-Glucuronidase Deficiency: Mucopolysaccharidosis VII….- 5.9. Multiple Sulfatase Deficiency.- 5.10. Steroid Sulfatase Deficiency.- 5.11. Other Glycosidase Deficiencies.- 5.12. Generalized Mucopolysaccharidoses (the “Mucolipidoses”).- 6. Effect of Lysosomal Glycosaminoglycan Storage on CNS Function and Prospects for Therapy.- References.- 17 Perspectives and Functional Implications.- 1. Biosynthesis and Metabolism.- 2. Axonal Transport.- 3. Synaptic Membranes.- 4. Cell-Cell Interactions and Neuronal Recognition.- References.- Appendix I: Developmental Changes in Complex Carbohydrates of Brain.- Appendix II: Turnover of Complex Carbohydrates in Rat Brain.- Appendix III: The Human Sphingolipidoses.