Nutritional Pathology

Pathobiochemistry of Dietary Imbalances

H. Sidransky

• Publisher: CRC Press
• Year: 2020
• Topic: Technology & Engineering
• eBook ISBN:
  9781000146608
• Subtopic: Food Science
• Index: Technology & Engineering

This book examines several recent, major developments in the field of nutritional pathology, providing enhanced, current understanding of the role that altered or disturbed nutrition plays in the pathogenesis of disease. It is intended for students in pathology, nutrition, and biochemistry.

1
Tryptophan

Unique Action by an Essential Amino Acid

Herschel Sidransky
George Washington University Medical Center Washington, D.C.

I. Introduction

Tryptophan has been acknowledged as an essential amino acid for many years, but only in recent years unique biological and metabolic properties have been attributed to this amino acid. Indeed, tryptophan is now known to be involved in regulatory control mechanisms of the central nervous system and of the liver. Thus, in addition to being an essential building block in proteins, tryptophan has other important effects that influence and regulate vital biological mechanisms. Indepth understanding of how one essential nutrient, such as tryptophan, acts in normal as well as in disease states is of importance. Such information should offer an opportunity whereby specific nutritional manipulation of a dietary component may be used in a rational way in the possible prevention and/or treatment of certain disease states.

II. Historical Data and Findings in Deficiencies

Historically, our knowledge of tryptophan began some 85 years ago. In 1901 Hopkins and Cole (1) isolated tryptophan from a pancreatic digest of casein. Its structure was established by Ellinger and Flamand in 1907 (2). In related nutritional studies, Willcock and Hopkins (3) 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 Mendel (4) demonstrated that zein plus tryptophan and lysine promoted normal growth in rats and thus established that these two amino acids were essential nutrients. Subsequently, in the 1950s Rose et al. (5) demonstrated that L-tryptophan was an essential dietary component for humans.

Early experiments with mice (3) and with rats (4) showed that tryptophan deficiency leads to a disturbance in growth. This amino acid was also necessary for the maintenance of nitrogen equilibrium in mature rats (6), mice (7), pigs (8), and dogs (9). A variety of pathological changes in experimental animals have been ascribed to tryptophan deficiency. Cataracts (10,11) and corneal vascularization (12) have been reported in animals subjected to tryptophan deficiency. Indeed, the only authenticated and reproducible example of experimental cataract caused by dietary deficiencies was that produced in guinea pigs and rats by feeding a diet deficient or devoid in tryptophan (13,14). Hematological manifestations of anemia (15), reduction in plasma proteins (16), fatty liver (16-22), and pancreatic atrophy (19) have been reported in tryptophan-deficient rats. Scoliosis has been reported after feeding fish a tryptophan-deficient diet (23,24).

The number of investigations into the biochemical changes in tissues and organs of experimental animals fed tryptophan-deficient diets has been limited. Most of these studies were concerned with changes in the liver. When tryptophan-deficient diets were fed either ad libitum or by force-feeding, differences in hepatic metabolism were observed (20). Also, when animals were fed other single essential amino acid-deficient diets, differences in the pathological and biochemical changes in the livers that were dependent upon the route of feeding—ad libitum or force-feeding—have been reported by others (25). In general, more marked changes were observed after force-feeding than after ad libitum-feeding of the deficient diets.

Samuels et al. (19) suggested that the fatty livers in rats force-fed a tryptophan-devoid diet were due to increased synthesis of hepatic lipid from carbon chains of amino acids that were not being used normally for protein synthesis. However other experimental studies did not support this suggestion (25). Patrick and Bennington (22) reported that the incorporation of labeled amino acids into liver lipids was greater in rats force-fed a tryptophan-devoid diet for 5 days compared with those force-fed a complete diet. Since fatty livers develop after force-feeding other single essential amino acid-devoid diets, other than a troptophan-devoid diet (25), the mechanism responsible may be similar regardless of the type of single deficiency. Several studies have suggested that stimulation of hepatic lipid synthesis may be responsible for the genesis of the fatty liver with single essential amino acid deficiency (26,27). However because a different mechanism, impairment of lipoprotein released (28,29), is considered to be involved in most cases of experimental fatty liver, further experimentation is necessary to clarify the mechanism with respect to amino acid deficiency. Conceivably, impairment of the synthesis of apolipoprotein resulting from a single amino acid deficiency could cause accumulation of triglycerides because of inadequate conversion of triglycerides to lipoprotein.

Hepatic protein synthesis has been evaluated in rats force-fed a tryptophan-devoid diet for 1 to 5 days by viewing the status of hepatic polyribosomes and by measuring labeled amino acid incorporation into hepatic and plasma proteins in vivo (30-32). The results revealed evidence of enhanced hepatic protein synthesis. Also, Patrick and Bennington (22) reported that in vivo hepatic protein synthesis was markedly increased in rats force-fed a tryptophan-devoid diet, but hepatic protein synthesis was only slightly increased in rats fed the deficient diet ad libitum when compared with rats fed comparable control diets. A relationship between the increased protein synthesis in the liver and the decreased protein synthesis in skeletal muscle has been described in rats force-fed a tryptophan-devoid diet (30,31) as well as with other single amino acid deficiencies (25).

In paired-feeding experiments Naito and Kandatsu (32,33) reported that when rats were fed a tryptophan-deficient diet for 2 to 22 days [³⁵S] methionine incorporation into hepatic proteins in vivo was increased over that in control rats. Nimni and Bavetta (34) also reported earlier, using ad libitum fed rats, that the incorporation of [¹⁴ glycine was enhanced in the livers of tryptophan-deficient rats after 13 days. However, Bocker et al. (35) reported that rats pair-fed a complete and a tryptophan-devoid diet for 5 to 15 days showed a diminished in vivo incorporation of a [³H]amino acid mixture into the hepatic proteins of the experimental animals when expressed as a percentage of uptake compared with controls. Thus the results of the majority of the experimental studies suggest that feeding a tryptophan-deficient diet, particularly under force-feeding conditions for 1 or more days, induces enhanced hepatic protein synthesis. These results are similar to those reported with rats force-fed other single essential amino acid-devoid diets (25).

III. Occurrence in Nature and in Mammals

Tryptophan is probably the indole derivative most widely distributed in nature. It is converted into many other substances of important biological significance. The many materials biogenetically related to tryptophan include nicotinic acid (a vitamin), serotonin (a neurohormone), indoleacetic acid (a phytohormone), some pigments found in the eyes of insects, and a number of alkaloids.

Although tryptophan is present in many proteins, it is present in only small amounts (much lower than most of the other amino acids) in mammalian hepatic proteins (36), Usually it is the least abundant amino acid in proteins. Indeed, a number of foodstuffs have been found to be deficient or limited in tryptophan, e.g., corn. On the other hand, since it is present in low concentration within most proteins, the requirement of tryptophan in the diet is low compared with that of the other amino acids, particularly the other essential amino acids. The knowledge that tryptophan is present in low levels in the diet and in the proteins of tissues and organs, as well as in their free amino acid pools including that in the blood, has been used in attempting to explain some of the effects of the amino acid. One prominent belief has been that tryptophan is an important, rate-limiting amino acid for various metabolic functions.

In 1950, Schurr et al. (37) determined the amino acid concentrations in various tissues of the rat. If these data are used to calculate tissue/ plasma ratios, it becomes apparent that the relative availability of plasma tryptophan to tissues is much less than that of the other amino acids. In 1957, McMenemy et al. (38) described a unique property of tryptophan: it was the only amino acid in human plasma that was largely bound to protein. This attribute, specifically the ratio of free to bound try...

Table of contents

• Cover
• Half Title
• Series Page
• Title Page
• Copyright Page
• Dedication
• Preface
• Contributors
• Contents
• 1. TRYPTOPHAN: UNIQUE ACTION BY AN ESSENTIAL AMINO ACID
• 2. EFFECTS OF NUTRITION ON TRANSCRIPTIONAL AND TRANSLATION AL CONTROLS OF PROTEIN SYNTHESIS IN LIVER
• 3. NUTRITIONALLY INDUCED PANCREATIC DISEASE
• 4. NUTRITION AND CARDIOVASCULAR DISEASE
• 5. PATHOLOGIC EFFECTS OF MALNUTRITION ON THE CENTRAL NERVOUS SYSTEM
• 6. DIETARY FIBERS: ASPECTS OF NUTRITION, PHARMACOLOGY, AND PATHOLOGY
• 7. PATHOLOGY OF CHOLINE DEFICIENCY
• 8. ROLE OF NUTRITIONAL STATUS IN DRUG METABOLISM AND TOXICITY
• 9. PATHOLOGICAL CHANGES ASSOCIATED WITH DRUG-INDUCED MALNUTRITION
• Index