Sphingolipid Biochemistry

Interest in and emphasis upon different aspects of the sphingolipids have, in general, followed the biochemical developments of the day. The early inves tigators were preoccupied principally with the isolation of "pure" compounds and structural elucidation. This historical perspective is found in the discus sion presented in Chapter 1 (Section 1. 1. 2 and Table III). Still, the isolation and structural characterization of glycolipids are the basic foundation of all our knowledge of enzymology, immunology, and cell biology. Recent infor mation obtained on structure has greatly affected the interpretation of various phenomena related to glycolipids. New structures suggest a new role of gly colipids as antigens and receptors. Ten years ago, only four neutral glycolipids and two gangliosides were known in human erythrocytes. We now know structures of at least twenty additional neutral glycolipids and ten additional gangliosides in human erythrocytes that are known to be important blood group, heterophil, and autoantigens. Erythrocytes are only one example of a cell type whose glycolipid profile has been extensively studied. Our defective knowledge in immunology and cell biology may be due to incomplete un derstanding of structural chemistry. Modern methodology based on methyla tion analysis, mass spectrometry, and enzymatic degradation has supple mented classical analysis based on clorimetry. Nuclear magnetic resonance spectroscopy is still in the development stage, but will eventually replace var ious chemical analyses. However, important future studies should be directed toward elucidating the organizational structure of glycolipids in membranes.

Contenu
1 Chemistry of Glycosphingolipids.- 1.1. Introduction.- 1.2. Isolation of Glycosphingolipids.- 1.3. Characterization of Glycosphingolipids.- 1.4. Structure of Glycosphingolipids.- 1.5. Chemical Synthesis and Modification of Sphingosines and Glycosphingolipids.- 1.6. Pioneers in Glycolipid Chemistry.- 1.7. References.- 2 Sphingolipid Metabolism.- 2.1. Sphingosine Bases.- 2.2. The Psychosines.- 2.3. Ceramide (N-Acylsphingosine).- 2.4. Galactosylceramide.- 2.5. Ceramide-galactoside-3-sulfate (Sulfatide).- 2.6. Glucosylceramide.- 2.7. Ganglioside Metabolism.- 2.8. Sphingomyelin.- 2.9. Biosynthesis of the Sphingolipids: Summary.- 3 The Sphingolipidoses.- 3.1. Farber's Lipogranulomatosis.- 3.2. Krabbe's Disease (Globoid Cell Leukodystrophy).- 3.3. Metachromatic Leukodystrophy.- 3.4. Gaucher's Disease.- 3.5. Fabry's Disease (Angiokeratoma Corporis Diffusium).- 3.6. The Gangliosidoses.- 3.7. Niemann-Pick's Disease.- 3.8. GM3 Gangliosidosis.- 3.9. General Comments.- 3.10. References.- 4 Glycosphingolipids in Cellular Interaction, Differentiation, and Oncogenesis.- 4.1. Introduction.- 4.2. Organization and Dynamic State of Glycohpids in Membranes.- 4.3. Glycolipids in Cellular Interaction and Differentiation.- 4.4. Role of Glycolipids in Cell Growth Control.- 4.5. Glycolipid Changes in Oncogenic Transformation: Deficiency in Glycolipid Function.- 4.6. Glycolipids as Possible Mediators of Immune Response.- 4.7. Postscript: Enigmas Concerning Glycohpid Functions.- 4.8. References.- 5 Glycolipid Antigens and Genetic Markers.- 5.1. Introduction.- 5.2. General Properties of Glycolipid Antigens.- 5.3. Heterophil Antigens.- 5.4. Glycolipids with Blood Group AB H Specificities.- 5.5. Glycolipids with Blood Group Lewis (Lea, Leb, Lec and Led) Specificities.- 5.6. Glycolipidswith Blood Group P, P1, and Pk Specificities.- 5.7. Glycolipids with Blood Group I and i Specificities.- 5.8. Glycolipids with Blood Group J-Antigen Specificity.- 5.9. Tissue-Specific and Tumor-Associated Glycolipid Antigens.- 5.10. Modification of Blood Group Antigens.- 5.11. Tissue-Specific or Organ-Specific Glycolipid Antigens.- 5.12. Glycolipid Antigens Associated with Autoimmune Processes.- 5.13. References.- 6 Glycosphingolipids as Receptors.- 6.1. Gangliosides and the Serotonin Receptor.- 6.2. Gangliosides and Acetylcholine.- 6.3. Gangliosides and Interferon.- 6.4. Gangliosides and Bacterial Toxins.- 6.5. Gangliosides and Lymphocyte Markers.- 6.6. Gangliosides and Glycoprotein Hormone Receptors.- 6.7. Conclusions.- 6.8. References.