Tryptophan Biochemical and Health Implications 1st Edition

Visit the link below to download the full version of this book:

https://medidownload.com/product/tryptophan-biochemical-and-health-implications-
1st-edition/

Click Download Now

 CRC Series in MODERN NUTRITION

TRYPTOPH AN
Biochemical and Health Implications

Herschel Sidransky

CRC PR E S S
Boca Raton London New York Washington, D.C.

© 2002 by CRC Press LLC

 Library of Congress Cataloging-in-Publication Data

Sidransky, Herschel, 1925-

Tryptophan : biochemical and health implications / Herschel Sidransky.
p. ; cm. -- (CRC series in modern nutrition)
Includes bibliographical references and index.
ISBN 0-8493-8568-7 (alk. paper)
1. Tryptophan. I. Title. II. Modern nutrition (Boca Raton, Fla.)
[DNLM: 1. Tryptophan--metabolism. QU 60 S569t 2001]
QP562.T7 S565 2001
612'.01575—dc21 2001043170
CIP

This book contains information obtained from authentic and highly regarded sources. Reprinted material
is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable
efforts have been made to publish reliable data and information, but the author and the publisher cannot
assume responsibility for the validity of all materials or for the consequences of their use.

Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic
or mechanical, including photocopying, microfilming, and recording, or by any information storage or
retrieval system, without prior permission in writing from the publisher.

All rights reserved. Authorization to photocopy items for internal or personal use, or the personal or
internal use of specific clients, may be granted by CRC Press LLC, provided that $1.50 per page
photocopied is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923
USA. The fee code for users of the Transactional Reporting Service is ISBN 0-8493-8568-7/01/
$0.00+$1.50. The fee is subject to change without notice. For organizations that have been granted a
photocopy license by the CCC, a separate system of payment has been arranged.

The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, for
creating new works, or for resale. Specific permission must be obtained in writing from CRC Press LLC
for such copying.

Direct all inquiries to CRC Press LLC, 2000 N.W. Corporate Blvd., Boca Raton, Florida 33431.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are
used only for identification and explanation, without intent to infringe.

Visit the CRC Press Web site at www.crcpress.com

© 2002 by CRC Press LLC

No claim to original U.S. Government works

International Standard Book Number 0-8493-8568-7
Library of Congress Card Number 2001043170
Printed in the United States of America 1 2 3 4 5 6 7 8 9 0
Printed on acid-free paper

© 2002 by CRC Press LLC

Series Preface

The CRC Series in Modern Nutrition is dedicated to providing the widest

possible coverage of topics in nutrition. Nutrition is an interdisciplinary,
interprofessional field par excellence. It is noted by its broad range and
diversity. We trust the titles and authorship in this series will reflect that
range and diversity.
Published for a scholarly audience, the volumes in the CRC Series in
Modern Nutrition are designed to explain, review, and explore present
knowledge and recent trends, developments, and advances in nutrition. As
such, they will also appeal to the educated general reader. The format for
the series will vary with the needs of the author and the topic, including,
but not limited to, edited volumes, monographs, handbooks, and texts.
Contributors from any bona fide area of nutrition, including the contro-
versial, are welcome.
We welcome the contribution Tryptophan: Biochemical and Health Implications
written authoritatively by Dr. Herschel Sidransky. He is a well-known expert
who has spent a large portion of his research career on the varied, and often
controversial, aspects of the metabolism of the amino acid tryptophan.

Ira Wolinsky, Ph.D.

University of Houston
Series Editor

© 2002 by CRC Press LLC

Preface

The author has been interested in selected aspects of L-tryptophan for many
years, including the effects of tryptophan deficiency and of the regulatory
effects of tryptophan upon protein synthesis. These interests stimulated the
author to attempt to obtain a comprehensive view of the role of L-tryptophan
in nutrition, biology, biochemistry, physiology, pharmacology, and toxicol-
ogy. The subject proved to be a major undertaking, and this book is the
culmination of this project. The chapters have been selected to present major
areas of the current knowledge of L-tryptophan’s role in biology and med-
icine. Each chapter presents an important aspect of how L-tryptophan, an
important indispensable amino acid, may act. Overall, it becomes apparent
that L-tryptophan and its metabolites are active and important compounds
that make major contributions to the vital functions and actions of cells of
a variety of tissues and organs. The role of L-tryptophan in health and disease
has become apparent from numerous investigative studies. Much is known,
yet there is much to discover. This book is designed to offer a comprehensive
overview of the subject and to stimulate others to contribute further
advances in this exciting area of biology and medicine.

© 2002 by CRC Press LLC

Author

Herschel Sidransky is Professor Emeritus

of Pathology at George Washington Uni-
versity Medical Center, Washington, D.C.
He earned his B.S. and M.S. degrees in
Biochemistry from Tulane University, and
an M.D. and training in pathology from
Tulane University and Charity Hospital of
Louisiana in New Orleans. Dr. Sidran-
sky’s research interests have focused on
nutritional deficiency diseases, experi-
mental chemical carcinogenesis, toxic
liver disease, and tryptophan metabolism.
He has authored more than 200 papers
and 95 abstracts in these areas. Dr. Sidransky has served on the editorial
boards of several leading medical journals and has been a member of the
American Society for Investigative Pathology, the American Society for
Nutritional Sciences, the American Society for Clinical Nutrition, the Amer-
ican Association for Cancer Research, the Society of Experimental Biology
and Medicine, and the United States and Canadian Academy of Pathology.

© 2002 by CRC Press LLC

Dedication and Acknowledgments

This book is dedicated to my co-worker of 40 years, Ms. Ethel Verney. Her

able and conscientious contributions to our investigative team have enabled
the research on tryptophan in my laboratory to progress and yield publica-
tions. Her long-standing contributions and devotion to research are hereby
acknowledged.
I also desire to acknowledge the support and encouragement of my wife,
Evelyn, and my children, Ellen and David, who have been understanding
and considerate during the years that I have devoted to teaching and
research. Their support was welcome and indeed vital.

© 2002 by CRC Press LLC

Contents

1 Tryptophan: A Unique Entity ........................................................ 1

2 Findings in Deficiency States ........................................................ 9

3 Genetics.......................................................................................... 19

4 Chemical Pathways, Protein Metabolism,

and Interrelationships .................................................................. 27

5 Blood and Hormonal Responses to Tryptophan

(Deficiency or Excess) ................................................................... 69

6 Tryptophan Effects or Influences on Biological Processes ...... 89

7 Effects or Influences on Organ Systems .................................. 163

8 Pharmacology and Selected Therapeutic Uses ........................ 189

9 Toxicity ......................................................................................... 209

10 Serotonin and Melatonin ........................................................... 219

11 The Eosinophilia Myalgia Syndrome:

A Tryptophan Tragedy................................................................ 225

12 Tryptophan: Past and Future Directions .................................. 251

© 2002 by CRC Press LLC

1
Tryptophan: A Unique Entity

CONTENTS
1.1 Historical Perspectives..................................................................................1
1.2 Occurrence in Nature....................................................................................2
1.2.1 Occurrence and Requirements ........................................................2
1.2.2 Synthesis .............................................................................................3
1.2.3 Chemistry ...........................................................................................4
References ................................................................................................. 5

1.1 Historical Perspectives

Our knowledge of tryptophan began some 100 years ago. In 1901 Hopkins
and Cole1 isolated tryptophan from a pancreatic digest of casein. Its structure
was established in 1907 by Ellinger and Flamand,2 who synthesized a sub-
stance that was identical to the tryptophan isolated by Hopkins and Cole.
It is noteworthy that about 50 years prior to the discovery of tryptophan
by Hopkins and Cole,1 aspects of tryptophan metabolism began to appear
in the research literature, when in 1853 Liebig discovered kynurenic acid
in dog urine.3 Subsequently, kynurenine, a tryptophan metabolite, was iden-
tified,4,5 and the relationship of kynurenic acid to tryptophan was under-
stood. A brief review on the discovery of tryptophan has been described by
Curzon.6
Although several other amino acids had been described before tryptophan,
it was the first demonstrated to be indispensable. Because tryptophan is
destroyed by acid hydrolysis of protein, tryptophan-deficient diets were
readily formulated, and this led to the demonstration that it was required
for growth of animals. In related nutritional studies, Willcock and Hopkins7
in 1906 observed that mice failed to grow and even died if their sole source
of dietary protein was zein. When tryptophan was added to the ration, the
lives of the animals were prolonged. A few years later, Osborne and Mendel8
demonstrated that zein plus tryptophan and lysine promoted normal
growth in rats, and they thus established that these two amino acids were

© 2002 by CRC Press LLC

2 Tryptophan: Biochemistry and Health Implications

essential nutrients. Subsequently, in the 1950s, Rose et al.9 demonstrated

that L-tryptophan was an essential dietary component for humans. Further
interest in tryptophan expanded when it was reported that tryptophan
could serve as a precursor of the vitamin niacin and NAD10,11 and of the
neurotransmitter serotonin.
Early experimentation with tryptophan dealt with animals exposed to
tryptophan-deficient diets. These nutritional studies served to stress the
importance of tryptophan in the diet in relation to disturbances in growth
and to observed pathologic changes. A few examples are presented below.
They reveal that tryptophan caught the interest of nutritionists, pathologists,
and clinicians, and they stress its nutritional role in medicine.
Early experiments with mice7 and with rats8 showed that tryptophan defi-
ciency leads to a disturbance in growth. This amino acid is also necessary for
the maintenance of nitrogen equilibrium in mature rats,12 mice,13 pigs,14 and
dogs.15 A variety of pathological changes in experimental animals have been
ascribed to tryptophan deficiency. Cataracts16,17 and corneal vascularization18
have been reported in animals subjected to tryptophan deficiency. Indeed,
the only authenticated and reproducible example of experimental cataracts
caused by dietary deficiencies was that produced in guinea pigs and rats by
feeding a diet deficient in or devoid of tryptophan.19,20 Hematological man-
ifestations of anemia,21 reduction in plasma proteins,22 fatty liver,22–27 and
pancreatic atrophy27 have been reported in tryptophan-deficient rats. Scoli-
osis has been reported after feeding fish a tryptophan-deficient diet.28,29
As a result of discussions during a tryptophan conference in 1971, an
international organization was formed with the purpose of furthering tryp-
tophan research by improving communication and collaboration among
workers through regular international meetings. The history of this organi-
zation, the International Study Group for Tryptophan Research (ISTRY), has
been compiled.30 Its most recent meeting, the ninth international meeting,
was held in Hamburg, Germany, in 1998; subsequent meetings are held every
three years. Many of these meetings have led to publications, which have
served as valuable reviews of the current status of research in tryptophan.31–39
These publications deal with historical events relating to tryptophan during
the past 30 years. They merit review for past and recent accomplishments
in tryptophan research involving metabolism, neurochemistry, nutrition, tox-
icology, and pathology.

1.2 Occurrence in Nature

1.2.1 Occurrence and Requirements
Tryptophan is probably the indole derivative most widely distributed in
nature. It is converted into many compounds of important biological
significance. Compounds biogenetically related to tryptophan include

© 2002 by CRC Press LLC

Tryptophan: A Unique Entity 3

nicotinic acid (a vitamin), serotonin (a neurohormone), indoleacetic acid

(a phytohormone), some pigments formed in the eyes of insects, and a
number of alkaloids.
Tryptophan is the least abundant amino acid in most proteins,40 account-
ing, on the average, for 1 to 1.5% of the total amino acids in typical plant
(1%) and animal (1.5%) proteins. A number of foodstuffs, such as corn, are
deficient or limited in tryptophan. Because it is present in low concentrations
in most tissue proteins, the requirement of tryptophan in the diet is low
compared to that of the other amino acids, particularly the other indispens-
able (essential) amino acids. In human infants, the requirement for growth
is roughly 12 to 40 mg/kg. In adult humans, the minimum daily requirement
has been estimated to be 250 mg/d in males and 160 mg/d in females.41
Considering the recommended daily allowance for protein is 56 g/d for an
adult man and 44 g/d for an adult woman, then this amount would supply
between 500 and 700 mg/d of tryptophan, assuming that the protein was of
high quality. A typical western diet may supply approximately 600 to 1200
mg L-tryptophan from protein intake.42
Despite the scarcity of tryptophan in dietary proteins, it rarely appears to
be the limiting amino acid for maintenance or growth when the dietary
amino acid source is from naturally occurring proteins. An example is the
corn protein zein, which is nearly devoid of tryptophan, yet lysine is limiting
for growth in this protein since the lysine content in zein in relation to its
requirement is the lowest of the indispensable (essential) amino acids. How-
ever, since tryptophan may not be limiting for growth in some poor quality
proteins, its supply may be insufficient for the normal functioning of the
many pathways that depend on an adequate supply or level of tryptophan.
One prominent view or belief has been that tryptophan, being present in
low levels in proteins, is an important rate-limiting amino acid for many
metabolic functions.
Schurr et al.43 reported the amino acid concentrations in various tissues of
the rat. Using these data to calculate tissue-to-plasma ratios, it becomes
apparent that the relative availability of plasma tryptophan to tissues is much
less than that of other amino acids. The finding, described elsewhere, that
tryptophan in serum or plasma can be present as free and bound (to plasma
albumin) is unique among amino acids,44 and this further limits or controls
the availability of tryptophan from the blood to organs or tissues, especially
the brain. Tryptophan differs from other amino acids in that its concentration
in plasma of rats increases (30 to 40%) after fasting, after insulin adminis-
tration, or after consuming a carbohydrate meal.45

1.2.2 Synthesis
Originally, L-tryptophan was first isolated from solutions of tryptic casein
hydrolysate by Hopkins and Cole in 1901. 1 Early studies utilized
L-tryptophan derived from natural sources. About 48 years later, in 1949,

© 2002 by CRC Press LLC

4 Tryptophan: Biochemistry and Health Implications

the first successful chemical synthesis of L-tryptophan was achieved.46 In the

early 1980s, chemical synthesis was fully replaced by fermentation meth-
ods.47 With fermentation methods, one differentiates between enzymatic
processes and de novo synthesis utilizing normal or modified metabolism of
microorganisms.48 Microbiological biosynthesis gained industrial impor-
tance following the development of efficient new strains through recombi-
nant DNA technology. In these processes, glucose, ethanol, or anthranilic
acid were used as the principle substrates, and L-tryptophan could be
obtained in yields of 10 g/l fermentation broth.48 Thus, L-tryptophan derived
in this manner has become available on the world market and is used for
foodstuff additives and for pharmacological uses. The significance of this
shift from obtaining L-tryptophan from natural sources to commercially
derived sources has had important consequences. One has been the reduc-
tion in world market price, allowing the increased use of tryptophan in
foodstuffs and for pharmaceutical uses. Another has been the undesirable
complication or side effect of the development of a significant human dis-
ease, eosinophilia myalgia syndrome, due to ingestion of L-tryptophan com-
mercially manufactured by a Japanese company, Showa Denko. This effect
is covered in Chapter 11.

1.2.3 Chemistry
Tryptophan is exceptional in the diversity of its biological functions, which
are covered throughout this book. It is appropriate to give limited attention
to the chemistry of tryptophan. Many complex transformations of tryp-
tophan in foods can occur. Also, a great diversity of derivatives can be
formed, some of which conceivably have antinutritional and toxic manifes-
tations. For details concerning such aspects of tryptophan, the reader is
referred to sources that cover these aspects in detail.49,50 The following
selected aspects are cited to emphasize some important chemical reactions
that may affect humans.
Many studies have been conducted on the stability of free or protein-bound
tryptophan during processing and storage. In general, chemical transforma-
tions of tryptophan are essentially a function of the temperature and the
duration of treatments. Specific modifications can be induced by the presence
of oxygen, water,51 food oxidizing lipids,52 vitamins,53 reducing sugars,54
carbonyl compounds,55 nitrites,56 sulfites,57 halogens,58 and radiation.59
The reactivity of the indole ring of tryptophan60 has attracted much interest
and attention. This aromatic, electron-rich nucleus is susceptible to oxidative
cleavage and to substitutions by a number of reagents. It can react as an
electron donor with aldehydes or carbocations.
Hydrophobic tryptophan residues present in the interior of food protein
molecules contribute to the optical and fluorescent properties of proteins.
Their spectral characteristics are considered to be important contributors in
the study of protein conformation.61

© 2002 by CRC Press LLC

Tryptophan: A Unique Entity 5

Severe treatments of tryptophan are required to cause a significant degra-

dation of tryptophan. In the absence of oxidizing agents, tryptophan is a
stable amino acid, even in strongly basic or acid conditions. During heat
treatment, such as industrial or home cooking in the presence of air or steam
sterilization, both free and bound tryptophan are relatively stable. However,
carboline formation occurs in the presence of carbonyl compounds or/and
at high temperatures (above 200°C, as in grill-cooking of meat or fish).
Carbolines (α-, β- and γ-) have been identified from the basic fraction of the
pyrolysates.62 Aspects of tryptophan reactions relating to Trp-P-1 (3-amino-
1,4-dimethyl-5H-pyrido-(4,3-b)indole) and Trp-P-2 (3-amino-1-methyl-5H-
pyrido-(4,3-b)indole) in relation to carcinogenesis are considered in
Chapter 6. Also, tryptophan-derived nitroso compounds, considered as
potential carcinogens, are attributed to the reaction of tryptophan with
nitrite, a meat-curing compound.56
For a concise review of the chemistry, see References 49, 50, and 63.

References
1. Hopkins, F. G. and Cole, S. W., A contribution to the chemistry of proteids.
Part I. A preliminary study of a hitherto undescribed product of tryptic diges-
tion, J. Physiol., 27, 48, 1901.
2. Ellinger, A. and Flamand, C., Uber Syntetisch Gewonnenes Tryptophan und
Einige Seiner Derivate, Hoppe-Seyle’s Z. Physiol. Chem., 55, 8, 1908.
3. Liebig, J., Kynurenic acid, Justus Liebys Ann. Chem., 86, 125, 1853.
4. Kotake, Y. and Masayama, T., Uber der Mechanismus dert Kynureninbildung
aus Tryptophan, Hoppe-Seyler’s Z. Physiol. Chem., 243, 237, 1936.
5. Butenandt, A., Weidel, W., Weichert, R., and von Derjugin, W., Kynurenine. Its
physiology, constitution and synthesis, Z. Physiol. Chem., 279, 27, 1943.
6. Curzon, G., Hopkins and the discovery of tryptophan, in Tryptophan Research
1986, Bender, D. A., Joseph, M. H., Kochen, W., and Steinhart, H., Eds., Walter
de Gruyter, Berlin, 1987, xxix-xxxvii.
7. Willcock, E. G. and Hopkins, F. G., The importance of individual amino acids
in metabolism. Observations on the effect of adding tryptophane to a diet in
which zein is the sole nitrogenous constituent, J. Physiol., 35, 88, 1906.
8. Osborne, T. B. and Mendel, L. B., Amino acids in nutrition and growth, J. Biol.
Chem., 17, 325, 1914.
9. Rose, W. C., Lambert, G. F., and Coon, M. J., The amino acid requirement of
man. VII. General procedures: The tryptophan requirement, J. Biol. Chem., 211,
815, 1954.
10. Krehl, W. A., Teply, L. J., Sarma, P. S., and Elvehjem, C. A., Growth retarding
effect of corn in nicotinic acid low rations and its counteraction by tryptophane,
Science, 101, 489, 1945.
11. Nishizuka Y. and Hayaishi, O., Studies on the biosynthesis of nicotinamide
adenine dinucleotide. I. Enzymatic synthesis of niacin ribonucleotides from
3-hydroxy-anthranilic in mammalian tissues, J. Biol. Chem., 238, 3369, 1963.

© 2002 by CRC Press LLC

6 Tryptophan: Biochemistry and Health Implications

12. Nasset, E. S. and Ely, M. T., Nitrogen balance of adult rats fed amino acids low
in L-, DL-, and D-tryptophan, J. Nutr., 51, 449, 1953.
13. Bauer, C. D. and Berg, C. P., The amino acids required for growth in mice and
the availability of their optical isomer, J. Nutr., 26, 51, 1943.
14. Mertz, E. T., Beeson, W. M., and Jackson, H. D., Classification of essential amino
acids for the weanling pig, Arch. Biochem. Biophys., 38, 121, 1952.
15. Rose, W. C. and Rice, E. E., The significance of the amino acids in canine
nutrition, Science, 90, 186, 1939.
16. Totter, J. R. and Day, P. L., Cataract and other ocular changes resulting from
tryptophane deficiency, J. Nutri., 24, 159, 1942.
17. Ferraro, A, and Roizin, L., Ocular involvement in rats on diets deficient in
amino acids. I. Tryptophan, Arch. Ophthalmol., 38, 331, 1947.
18. Sydenstricker, V. P., Hall, W. K., Bowles, L. L., and Schmidt, H. L., Jr., The
corneal vascularization resulting from deficiencies of amino acids in the rat,
J. Nutr., 34, 481, 1947.
19. Von Sallman, L., Reid, M. E., Grimes, P. A., and Collins, E. M., Tryptophan-
deficiency cataract in guinea pigs, Arch. Ophthalmol., 62, 662, 1959.
20. Van Heyningen, R., Experimental studies on cataract, Invest. Ophthalmol., 15,
685, 1976.
21. Albanese, A. A., Holt, L. E., Jr., Kajdi, C. N., and Frankston, J. E., Observations
on tryptophane deficiency in rats. Chemical and morphological changes in the
blood, J. Biol. Chem., 148, 299, 1943.
22. Cole, A. S. and Scott, P. P., Tissue changes in the adult tryptophan-deficient rat,
Br. J. Nutr., 8, 125, 1954.
23. Scott, E. B., Histopathology of amino acid deficiencies. IV. Tryptophan, Am. J.
Pathol., 31, 1111, 1955.
24. Adamstone, F. B. and Spector, H., Tryptophan deficiency in the rat. Histologic
changes induced by forced feeding of an acid hydrolyzed casein diet, Arch.
Pathol., 49, 173, 1950.
25. Van Pilsum, J. F., Speyer, J. F., and Samuels, L. T., Essential amino acid deficiency
and enzyme activity, Arch. Biochem., 68, 42, 1957.
26. Spector, H. and Adamstone, F. B., Tryptophan deficiency in the rat induced by
forced feeding of an acid hydrolyzed casein diet, J. Nutr., 40, 213, 1950.
27. Samuels, L. T., Goldthorpe, H. C., and Dougherty, T. F., Metabolic effects of
specific amino acid deficiencies, Fed. Proc., 10, 393, 1951.
28. Kloppel, T. M. and Post, G., Histological alterations in tryptophan-deficient
rainbow trout, J. Nutr., 105, 861, 1975.
29. Poston, H. A. and Rumsey, G. L., Factors affecting dietary requirement and
deficiency signs of L-tryptophan in rainbow trout, J. Nutr., 113, 2568, 1983.
30. Brown, R. R., A brief history of ISTRY, in Progress in Tryptophan and Serotonin
Research 1986, Bender, D. H., Joseph, M. H., Kochen, W., and Steinhart, H., Eds.,
Walter de Gruyter, Berlin, 1987, xix-xx.
31. Brown, R. R., Ed., Tryptophan metabolism, Am J. Clin. Nutr., 24, 653-851, 1971.
32. Allegri, G., De Antoni, A., and Costa, C., Eds., Tryptophan metabolism: Bio-
chemistry, pathology and regulation, Acta Vitaminol. Enzymol., 29, 1–345, 1974.
33. Hayaishi, O., Ishimura, Y., and Kido, O., Eds., Biochemical and medical aspects
of tryptophan metabolism, in Developments in Biochemistry, Elsevier/North Hol-
land Biochemical Press, 1980, 1–373.
34. Schlossberger, H. G., Kochen, W., Lingen, B., and Steinhart, H., Eds., Progress
in Tryptophan Research, Walter de Gruyter, Berlin, 1984.

© 2002 by CRC Press LLC

Tryptophan: A Unique Entity 7

35. Bender, D. A., Joseph, M. H., Kochen, W., and Steinhart, H., Eds., Progress in
Tryptophan and Serotonin Research 1986, Walter de Gruyter, Berlin, 1987, 1–429.
36. Schwarcz, R., Young, S. N., and Brown, R. R., Eds., Kynurenine and serotonin
pathways — progress in tryptophan research, Adv. Exp. Med. Biol., 294, 1–715,
1991.
37. Kochen, W. and Steinhart, H., Eds., L-tryptophan, Current Prospects in Medicine
and Drug Safety, Walter de Gruyter, Berlin, 1994.
38. Filippini, G. A., Cosla, C. V. L., and Bertazzo, A., Eds., Recent advances in
tryptophan research, Adv. Exp. Med. Biol., 398, 1996.
39. Huether, G., Kochen, W., and Steinhart, H., Eds., Tryptophan, serotonin, and
melatonin. Basic aspects and applications, Adv. Exp. Med. Biol., 467, 1999.
40. Block, R. J. and Weiss, K. W., The amino acid composition of proteins, in Amino
Acid Handbook, Charles C Thomas, Springfield, 1956, 288.
41. Harper, A. E., Human amino acid and nitrogen requirements as the basis for
evaluation of nutritional quality of protein, in Food Proteins, Whitaker, J. R. and
Tannenbaum, S. R., Eds., Avi Publishing Co., Inc., Westport, 1977, 363–386.
42. Recommended Dietary Allowances, 9th rev. ed., National Academy Press, Wash-
ington, D.C., 1980, 43.
43. Schurr, P. E., Thompson, H. T., Henderson, L. M., and Elvehjem, C. A., Deter-
mination of free amino acids in rat tissues, J. Biol. Chem., 182, 39, 1950.
44. Mcmenemy, R. M., Lund, C. C., and Oncley, J. L., Unbound amino acid con-
centrations in human blood plasmas, J. Clin. Invest., 36, 1672, 1957.
45. Fernstrom, J. D. and Wurtman, R. J., Elevation of plasma tryptophan by insulin,
Metabolism, 21, 337, 1972.
46. Hellmann, H., Die tynthesen des Tryptophans, Angew. Chem., 61, 352, 1949.
47. Gerhartz, W., Ed., Ullman’s Encyclopedia of Industrial Chemistry, 5th ed., VCH
Verlagsgesellschaft mbH, Weinheim, 985, 73–74.
48. Jeschkeit, H. and Griehl, C., Aminosauren, in Lebensmittel-Biotechnologie, Rutt-
loff, H., Ed., Akademie Verlag GmbH, Berlin, 1991, 454-481.
49. Greenstein, J. P. and Winitz, M., Chemistry of the Amino Acids, Vol. 3, John Wiley
& Sons, New York, 1961, 2316–2347.
50. Meister, A., Biochemistry of the Amino Acids, Vols. 1 and 2, 2nd ed., Academic
Press, New York, 1965, 841–884.
51. Leahy, M. M. and Warthesen, J. J., The influence of Maillard browning and
other factors on the stability of free tryptophan, J. Food Process. Preserv., 7,
25, 1983.
52. Krogull, M. K. and Fennema, O., Oxidation of tryptophan in the presence of
oxidizing methyl linoleate, J. Agric. Food Chem., 35, 66, 1987.
53. Kanner, J. D, and Fennema, O., Photo-oxidation of tryptophan in the presence
of riboflavin, J. Agric. Food Chem., 35, 71, 1987.
54. Orsi, F. and Dwaechak, E., Study of the Maillard reaction occurring between
methionine and tryptophan on the one hand and glucose on the other. Part II.
Studies in melts, Acta Aliment., 7, 1, 1978.
55. McLaren, J. A., The reaction of tryptophan and derivatives with some 1,3-
dicarbonyl compounds, Aust. J. Chem., 30, 2045, 1977.
56. Kinae, N., Isolation of beta-carboline derivatives from Maillard reaction mix-
tures that are mutagenic after nitrite treatment, Dev. Food Sci., 13, 343, 1986.
57. Yang, S. F., Destruction of tryptophan during aerobic oxidation of sulfite ions,
Environ. Res., 6, 395, 1973.

© 2002 by CRC Press LLC

8 Tryptophan: Biochemistry and Health Implications

58. Bercz, J. P. and Bana, R., Oxidation of nutrients in the presence of chlorine
based disinfectants used in drinking water treatment, Toxicol. Lett., 34, 141, 1986.
59. Garrison, W. M., Reaction mechanisms in the radiolysis of peptides, polypep-
tides, and proteins, Chem. Res., 381, 1987.
60. Fontana, A., Advances in chemical modifications of tryptophan in peptides and
proteins, in Progress in Tryptophan and Serotonin Research, Schlossberger, H. G.,
Kochen, W., Linzen, B., and Steinhart, H., Eds., de Gruyter, Berlin, 1984, 829.
61. Wolfenden, R., How hydrophilic is tryptophan?, Trends Biochem. Sci., 11,
70, 1986.
62. Sugimura, T., Studies on environmental chemical carcinogenesis in Japan,
Science, 233, 312, 1986.
63. Friedman, M. and Cua, J.-L., Chemistry, analysis, nutritional value, and toxicity
of tryptophan in food. A review, J. Agric. Food Chem., 36, 1079, 1988.

© 2002 by CRC Press LLC