Table Of ContentComplex
Carbohydrates
of Nervous Tissue
Complex
Carbohydrates
of Nervous Tissue
Edited by
Richard U. Margolis
New York University Medical Center
New York, New York
and
Renee K. Margolis
State University of New York
Downstate Medical Center
Brooklyn, New York
Plenum Press . New York and London
Library of Congress Cataloging in Publication Data
Main entry under title:
Complex carbohydrates of nervous tissue.
Includes bibliographical references and index.
1. Carbohydrates. 2. Complex compounds. 3. Nerve tissue. I. Margolis, Richard
U. II. Margolis, Renee K. [DNLM: 1. Neurochemistry. 2. Gangliosides. 3. Glyco
proteins. 4. Glycosaminoglycans. 5. Anions. WLl04 C737)
QP701.C58 599'.01'88 78-26881
ISBN-13: 978-1-4613-2927-5 e-ISBN-13: 978-1-4613-2925-1
DOl: 10.1007/978-1-4613-2925-1
©1979 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1979
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
Contributors
Richard T. Ambron • Department of Anatomy, Division of Neurobiology
and Behavior, College of Physicians and Surgeons, Columbia Uni
versity, New York, New York
Glyn Dawson. Departments of Pediatrics and Biochemistry, Joseph P.
Kennedy, Jr., Mental Retardation Research Center, University of
Chicago, Chicago, Illinois
J. S. Elam. Department of Biological Science, Florida State University,
Tallahassee, Florida
Giuliana Giannattasio. Department of Pharmacology and CNR Center of
Cytopharmacology, University of Milan, Milan, Italy
George W. Jourdian. Rackham Arthritis Research Unit and Department of
Biological Chemistry, University of Michigan, Ann Arbor, Michigan
O. K. Langley. Institute of Neurology, London, England (Present address:
Institut de Chimie Biologique de la Faculte de Medecine, Strasbourg,
France)
Robert W. Ledeen • Saul R. Korey Department of Neurology and Depart
ment of Biochemistry, Albert Einstein College of Medicine, Bronx,
New York
Su-Chen Li. Department of Biochemistry and Delta Primate Research
Center, Tulane Medical Center, New Orleans, Louisiana
Yu-Teh Li. Department of Biochemistry and Delta Primate Research
Center, Tulane Medical Center, New Orleans, Louisiana
Henry R. Mahler. Molecular and Cellular Biology Program and Depart
ment of Chemistry, Indiana University, Bloomington, Indiana
Renee K. Margolis. Department of Pharmacology, State University of
New York, Downstate Medical Center, Brooklyn, New York
Richard U. Margolis. Department of Pharmacology, New York Uni
versity School of Medicine, New York, New York
Marie-France Maylie-Pfenninger. Department of Developmental Genetics,
Sloan-Kettering Institute for Cancer Research, New York, New York
v
vi Contributors
Barbara J. McLaughlin. Department of Anatomy, University of Tennessee
Center for the Health Sciences, Memphis, Tennessee
Jacopo Meldolesi. Department of Pharmacology and CNR Center of
Cytopharmacology, University of Milan, Milan, Italy
Karl H. Pfenninger. Department of Anatomy, College of Physicians and
Surgeons, Columbia University, New York, New York
Richard H. Quarles. Section on Myelin and Brain Development, Develop
mental and Metabolic Neurology Branch, NINCDS, National Institutes
of Health, Bethesda, Maryland
Abraham Rosenberg. Department of Biological Chemistry, M. S. Hershey
Medical Center, Hershey, Pennsylvania
M. G. Scher. Department of Biochemistry, University of Maryland School
of Medicine, Baltimore, Maryland
James H. Schwartz. Departments of Physiology and Neurology, Division
of Neurobiology and Behavior, College of Physicians and Surgeons,
Columbia University, New York, New York
Robert R. Townsend. Department of Biochemistry and Delta Primate
Research Center, Tulane Medical Center, New Orleans, Louisiana
c.
J. Waechter. Department of Biochemistry, University of Maryland
School of Medicine, Baltimore, Maryland
John G. Wood. Department of Anatomy, University of Tennessee Center
for the Health Sciences, Memphis, Tennessee
Antonia Zanini. Department of Pharmacology and CNR Center of Cyto
pharmacology, University of Milan, Milan, Italy
Preface
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.
Although methods developed for the study of these compounds in other
tissues have often been of considerable value in the investigation of nervous
tissue complex carbohydrates, one cannot expect the properties and func
tional roles of glycoconjugates to be similar throughout the body. For this
reason, attempts to directly carryover to nervous tissue certain supposedly
"general" principles gained from the study of cartilage or immunoglobulins,
for example, may be somewhat analogous to exploring Italy with a map of
France. The neurochemist studying complex carbohydrates must therefore
keep a very open mind, but in compensation for the delays involved in
covering largely uncharted territory, there are also numerous instances
in which structur:ll features, localizations, or other properties of these
compounds appear to be unique to nervous tissue or were first identified
there.
Up to now much of the research on nervous tissue glycoconjugates has
necessarily been of a somewhat preliminary nature, including studies aimed
vii
viii Preface
at obtaining initial information on their structure, distribution, and metabo
lism. Only by building on a firm foundation of this type will it be possible
to formulate and test relevant hypotheses concerning their functional roles.
However, the great strides made in the past 5-10 years suggest that this is
an opportune time to take stock of where we stand now and which lines
of investigation appear most profitable to pursue further. It is therefore
hoped that the present volume will be of value not only to neurochemists
and neurobiologists, but also to the larger group of investigators interested
in complex carbohydrates from other standpoints, and for whom a sum
mary of current knowledge in this area may provide pertinent insights into
the biological roles of these highly versatile compounds.
Richard U. Margolis and Renee K. Margolis
New York
Contents
Chapter 1
Structure and Distribution of Gangliosides
Robert W. Ledeen
1. Introduction .............................................. 1
2. Structures ................................................ 2
2.1. Classification ......................................... 2
2.2. Ganglio Series ........................................ 3
2.3. Lacto Series .......................................... 11
2.4. Hematosides .......................................... 11
2.5. Lipophilic Components................................. 12
3. Distribution............................................... 13
3.1. Gross Compartmentalization in the Nervous System ....... 13
3.2. Brain Cells ........................................... 14
3.3. Brain Subcellular Fractions ............................. 16
References .................................................. 19
Chapter 2
Biosynthesis and Metabolism of Gangliosides
Abraham Rosenberg
1. Introduction: Location and Types of Gangliosides ............. 25
2. Biosynthesis of Brain Gangliosides ........................... 26
2.1. Synthesis by Glycosyltransferases ........................ 26
2.2. Sequential Glycosylations ............................... 28
2.3. Glycosylation in Vivo .................................. 32
2.4. From Synthetic Machinery to Membrane Structure ........ 33
3. Turnover of Brain Gangliosides .............................. 33
3.1. Turnover in Toto ...................................... 33
3.2. Developmental Correlations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
ix
x Contents
4. Catabolism of Nervous System Gangliosides .................. 34
4.1. Lysosomal Glycohydrolases and Plasma Membrane Sialidase
(Neuraminidase) ....................................... 34
4.2. Deficiencies in Catabolic Glycohydrolases ................. 35
4.3. Speculations on Sialidase Resistance of GM1 •• • • • • • • • • • • • • 35
5. Influence of Physicochemical Properties on Metabolism . . . . . . . 36
5.1. Possibility of Self-Aggregation .......................... 36
5.2. Receptor Functions .................................... 37
References .................................................. 39
Chapter 3
Structure and Distribution of Glycoproteins
and Glycosaminoglycans
Renee K. Margolis and Richard U. Margolis
1. Introduction .............................................. 45
2. Structure ................................................. 46
2.1. Composition and Structure of Nervous Tissue Glycoproteins . 46
2.2. Composition and Structure of Brain Glycosaminoglycans ... 55
3. Distribution ............................................... 60
3.1. G Iycoproteins ......................................... 60
3.2. Glycosaminoglycans ................................... 64
4. Conclusions ............................................... 68
References .................................................. 68
Chapter 4
Biosynthesis of Glycoproteins
C. J. Waechter and M. G. Scher
I. Introduction .............................................. 75
2. Sugar Nucleotide: Glycoprotein Glycosyltransferases ........... 76
2.1. N-Acetylgalactosaminyltransferases ...................... 76
2.2. Mannosyltransferases .................................. 78
2.3. N-Acetylglucosaminyltransferases ........................ 79
2.4. Galactosyltransferases .................................. 80
2.5. N-Acetylneuraminyltransferases ......................... 81
2.6. Fucosyltransferases .................................... 83
2.7. Glucosyltransferases ................................... 83
