Ciba Foundation Symposium 22 - Aromatic Amino Acids in the Brain

396 Pages·1974·7.44 MB·English

Aromatic Amino Acids
in the Brain
The Ciba Foundation for the promotion of international cooperation in
medical and chemicul research is a scientific and educational charity established by
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Aromatic Amino Acids
in the Brain
Ciba Foundation Symposium 22 (new series)
1974
Elsevier . Excerpta Medica . North-Holland
Associated Scientific Publishers . Amsterdam . London . New York
0 Copyright 1974 Ciba Foundation
All rights reserved. No part of this publication may be reproduced, stored in a retrieval
system or transmitted, in any form or by any means, electronic, mechanical, photocopying,
recording, or otherwise, without permission in writing from the publishers.
ISBN Excerpta Medica 90 219 4023 x
ISBN American Elsevier 0-444-15 019-6
Library of Congress Catalog Card Number 73-91643
Published in 1974 by Associated Scientific Publishers, P.O. Box 211, Amsterdam, and
American Elsevier, 52 Vanderbilt Avenue, New York, N.Y. 10017.
Suggested series entry for library catalogues: Ciba Foundation Symposia.
Suggested publisher’s entry for library catalogues: Associated Scientific Publishers.
Ciba Foundation Symposium 22 (new series)
Printed in The Netherlands by Mouton & CO,T he Hague
Contents
R. J. WURTMAN Chairman’s introduction I
H. N. MUNRO Control of plasma amino acid concentrations 5
Discussion 18
A. LAJTHA Amino acid transport in the brain ivl vivo and in vitro 25
Discussion 4 1
J. AXELROD and I. M. SAAVEDRA Octopamine, phenylethanolamine, phenyl-
ethylamine and tryptamine in the brain 51
Discussion 60
P. MANDEL and D. AUNIS Tyrosine aminotransferase in the brain 67
Discussion 79
s. KAUFMAN Properties of pterin-dependent aromatic amino acid hydroxyl-
ases 85
Discussion 108
A. CARLSSON The in vivo estimation of rates of tryptophan and tyrosine hy-
droxylation: effects of alterations in enzyme environment and neuronal
activity 117
Discussion 126
N. WEINER,F .-L. LEE, J. c. WAYMIRE and M. POSIVIATA The regulation of tyrosine
hydroxylase activity in adrenergic nervous tissue 135
Discussion 147
J. D. FERNSTROM, B. K. MADRAS, H. x. MUNRO and R. J. WURTMAN Nutritional
control of the synthesis of 5-hydroxytryptamine in the brain 153
Discussion 166
VI CONTENTS
A. PARFITT and D. G. GRAHAME-SMITH The transfer of tryptophan across the
synaptosome membrane 175
Discussion 192
A. T. B. MOIR Tryptophan concentration in the brain 197
G. L. GESSA and A. TAGLIAMONTE Serum free tryptophan: control of brain con-
centrations of tryptophan and of synthesis of 5-hydroxytryptamine 207
G. CURZON and P. J. KNOTT Fatty acids and the disposition of tryptophan 217
Discussion of the three preceding papers 230
M. BULAT Monoamine metabolites in the cerebrospinal fluid: indicators of the
biochemical status of monoaminergic neurons in the cerebral nervous
system 243
Discussion 257
s. H. BARONDES Do tryptophan concentrations limit protein synthesis at
specific sites in the brain? 265
Discussion 275
s. s. OJA, P. LAHDESMAKI and M.-L. VAHVELAINEN Aromatic amino acid supply
and protein synthesis in the brain 283
Discussion 294
S. ROBERTS Effects of amino acid imbalance on amino acid utilization, protein
synthesis and polyribosome function in cerebral cortex 299
Discussion 3 18
B. F. WEISS, L. E. ROEL, H. N. MUNRO and R. J. WURTMAN L-Dopa, polysomal
aggregation and cerebral synthesis of protein 325
Discussion 332
L. MAhRE, P. R. HEDWALL and P. C. WALDMEIER a-Methyldopa, an unnatural
aromatic amino acid 335
E. M. GAL Synthetic p-halogenophenylalanines and protein synthesis in the
brain 343
Discussion 354
T. L. SOURKES Effects of a-methyltryptophan on tryptophan, 5-hydroxytrypt-
amine and protein metabolism in the brain 361
Discussion 378
R. J. WURTMAN Chairman’s closing remarks 381
Index of contributors 385
Subject index 387
Participants
Symposium on Aromatic Amino Acids in the Brain held at the Ciba Foundation
on 15-17th May, 1973
R. J. WURTMAN (Chairman) Laboratory of Neuroendocrine Regulation,
Department of Nutrition and Food Science, Massachusetts Institute of
Technology, Cambridge, Massachusetts 021 39, USA
"J. AXELROD Laboratory of Clinical Science, Mental Health Intramural
Research Program, National Institute of Mental Health, 9000 Rockville
Pike, Bethesda, Maryland 20014, USA
s. H. BARONDES Department of Psychiatry, School of Medicine, University of
California San Diego, PO Box 109, La Jolla, California 92037, USA
M. BULAT Department of Pharmacology, Chicago Medical School, 2020 West
Ogden Avenue, Chicago, Illinois 60612, USA
A. CARLSSON Department of Pharmacology, University of Goteborg, Fack,
S-400 33 Goteborg 33, Sweden
G. CURZON Department of Neurochemistry, Institute of Neurology, The
National Hospital, Queen Square, London WIC 3BG
D. ECCLESTON MRC Brain Metabolism Unit, University of Edinburgh,
1 George Square, Edinburgh EH8 9JZ
D. FELIX Institut fur Hirnforschung der Universitat Zurich, August-Forel-
Strasse 1, CH-8008 Zurich, Switzerland
J. FERNSTROM Department of Nutrition and Food Science, Massachusetts
Institute of Technology, Cambridge, Massachusetts 021 39, USA
E. M. GAL Department of Psychiatry, State Psychopathic Hospital, The Uni-
versity of Iowa, 500 Newton Road, Iowa City, Iowa 52240, USA
G. L. GESSA Istituto di Farmacologia, UniversitA di Cagliari, Via Porcell 4,
09100 Cagliari, Sardinia
* Unable to attend.
VIII PARTICIPANTS
J. GLOWINSKI ColEge de France, Laboratoire de Biologie MolCculaire, Groupe
de Neuropharmacologie Biochimique, 11 place Marcelin-Berthelot, 75
Paris 5e, France
D. G. GRAHAME-SMITH MRC Clinical Pharmacology Unit, University Depart-
ment of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road,
Oxford OX2 6HE
s. KAUFMAN Laboratory of Neurochemistry, Mental Health Intramural
Research Program, National Institute of Mental Health, 9000 Rockville
Pike, Bethesda, Maryland 20014, USA
A. LAJTHA New York State Research Institute for Neurochemistry and Drug
Addiction, Ward’s Island, New York 10035, USA
L. MATTRE Biological Research Laboratories, Pharmaceuticals Division, CIBA-
GEIGY Limited, CH-4002 Basel, Switzerland
P. MANDEL Centre de Neurochimie, Centre National de la Recherche Scien-
tifique, 11 rue Humann, 67085 Strasbourg Cedex, France
A. T. B. MOIR Scottish Home and Health Department, St Andrew’s House,
Edinburgh EHl 3DE
H. N. MUNRO Department of Nutrition and Food Science, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02139, USA
S. s. OJA Department of Biomedicine, University of Tampere, Teiskontie 37,
SF-33520 Tampere 52, Finland
S. ROBERTS Department of Biological Chemistry, University of California,
School of Medicine, The Center for the Health Sciences, Los Angeles,
California 90024, USA
M. SANDLER Bernhard Baron Memorial Research Laboratories, Department
of Chemical Pathology, Queen Charlotte’s Maternity Hospital, Goldhawk
Road, London W6 OXG
D. F. SHARMAN ARC Institute of Animal Physiology, Babraham, Cambridge
CB2 4AT
T. L. SOURKES Departments of Psychiatry and Biochemistry, McGill University,
1033 Pine Avenue West, Montreal 112, Quebec, Canada
N. WEINER Department of Pharmacology, University of Colorado Medical
Center, 4200 East Ninth Avenue, Denver, Colorado 80220, USA
Editors: G. E. w. WOLSTENHOLME and DAVID w. FITZSIMONS
Editors’ note
As far as possible, we have followed the Recommendations of the IUPAC-IUB
Commission on Biochemical Nomenclature and the conventions of the Bio-
chemical Journal (see Instructions to Authors). In view of the variety of liames
in common use, we append a list of the trivial and systematic names of some
compounds mentioned in the book.
dopa: 3-(3,4-dihydroxyphenyl)alanine (I)
dopamine: 2-(3,4-dihydroxyphenyl)ethylamine, i.e. 4-(2-aminoethyl)benzene-
1,2-diol
homogentisic acid: 2,5-dihydroxyphenylacetica cid
homovanillic acid 4-hydroxy-3-methoxyphenylacetica cid
6-hydroxydopa : 3-(2,4,5-trihydroxyphenyl)alanine
5-hydroxyindoleacetic acid
(5HIAA): 5-hydroxy-3-indolylacetica cid (11)
p-hydroxymandelic acid : hydroxy(4-hydroxypheny1)acetic acid
5-hydroxytryptamine
(5HT, serotonin); 2-(5-hydroxy-3-indolyl)ethylamine,i .e. 3-(2-aminoethyl)-5-indolol
5-hydroxytryptophol : 2-(5-hydroxy-3-indolyl)ethanol
a-ketoglutarate: 2-oxoglutarate
melatonin: N-acetyl-2-(5-methoxy-3-indolyl)ethylamine
a-methyldopa : 3-(3,4-dihydroxyphenyl)-2-methylalanine
MK486 ~-3-(3,4-dihydroxyphenyl)-2-hydrazino-2-methylpropioniacc id
noradrenaline 2-amino-l-(3,4-dihydroxyphenyl)ethanol,i. e. 4-(2-amino-l-
(norepinephrine) : hydroxyethyl)benzene-1,2-diol
NSD 1015 3-hydroxybenzylhydrazine,i .e. 3-hydrazinomethylphenol
NSD 1055 4-bromo-3-hydroxybenzyloxyamine, i.e. 5-aminooxy-3-bromo-
phenol
octopamine: 2-amino-l-(4-hydroxyphenyl)eth anol
phenylethanolamine : 2-amino-1-phenylethanol
pterin : 2-amino-4-pteridinol
tryptamine: 2-(3-indolyl)ethylamine
tyramine : 4-(2-aminoethyl)phenol
rn-tyramine: 3-(2-aminoethyl)phenol
(I) CH2*CH(NHz)*COOH (I[)
0.. H OCH,.COOH ~
OH H
Aromatic Amino Acids in the Brain
Ciba Foundation
CowriQht0 1974 Ciba Foundation
Chairman’s introduction
R. J. WURTMAN
Laboratory of Neuroendocrine Regulation, Department of Nutrition and Food Science,
Massachusetts Institute of Technology, Cambridge, Massachusetts
It is no secret to this community that aromatic amino acids have a special
significance in the functions of the brain. By ‘aromatic amino acids’ we are
forced to restrict our attention to three such compounds : phenylalanine, tyrosine
and tryptophan. (Tt is not that histidine is not important, but rather that the
time at our disposal is not infinite.) These compounds are extremely important
in normal brain function, in the pathophysiology of various disease states and
in the responses of the brain to various drugs. Like the other amino acids present
in dietary protein, they circulate in the blood and are taken up into brain, where
they charge transfer RNAs and are subsequently incorporated into peptides and
proteins. Furthermore, these amino acids can be hydroxylated within specific
neurons, generating other amino acids which in turn are decarboxylated to yield
biogenic monoamines that function as neurotransmitters. One can make an
impressive list of brain diseases in which they participate, starting with phenyl-
ketonuria, the prototypic inborn error of metabolism. Other brain diseases have,
in recent years, been shown to respond favourably to treatment with hydroxy-
lated amino acids not normally found in the circulation-L-dopa and L-5-hydr-
oxytryptophan. The lack of adequate amounts of dietary protein (Shoemaker&
Wurtman 1971) or the chronic consumption of proteins like corn that contain
unfavourable proportions of these amino acids (Fernstrom & Wurtman 1971)
can interfere with normal brain function and behaviour; these disturbances
coincide with changes in the concentrations of the monoamine neurotransmitters
in the brain and urine (Hoeldtke & Wurtman 1973).
Considering this basic recognition of the importance to brain of the aromatic
amino acids, some of us thought that it might be useful to try to bring together
representatives of the three communities of scientists who study these com-
pounds. The first such community comprises those who are concerned with the
factors that control the concentrations of these aromatic amino acids in the