Tryptophan deficiency

Deficiency of essential amino acid precursors in the diet can cause a dysregulation of neurotransmitter activity (e.g, L-tryptophan deficiency causes a decrease in 5-HT and melatonin synthesis and activity). Deficiency in essential fatty acids (e.g, omega-3 fatty acids) can cause a dysregulation of neurottansmitter... 

Patients show signs of tryptophan deficiency despite a healthy diet as well as elevated urinary and fecal excretion of the neutral amino acids. 

Dietary protein deficiency, especially a lack of essential amino acids, has a long-term effect on regulatory mechanisms. Tryptophan plays a significant role here. Tryptophan deficiency leads to decreased protein synthesis, which is reversible solely by dietary supplementation of tryptophan even during inanition. The tryptophan effect occurs rapidly following the stimulation of nuclear RNA synthesis. (89) (s. fig. 3.4)... 

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... 

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. 

Totter, J. R. and Day, P. L., Cataract and other ocular changes resulting from tryptophane deficiency, J. Nutri., 24, 159, 1942. 

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. 

Kloppel, T. M. and Post, G., Histological alterations in tryptophan-deficient rainbow trout, /. Nutr., 105, 861, 1975. 

Hematological manifestations of anemia8 and reduction in plasma proteins9 have been reported with tryptophan deficiency. 

Fatty liver has been reported in rats fed tryptophan-deficient diets.9-14 Adam-stone and Specter11 and Samuels et al.14 observed a rapid development of fatty liver with a periportal distribution of the lipid in rats after the animals were force-fed a tryptophan-devoid diet. 

Scoliosis has been reported after feeding fish a tryptophan-deficient diet.1617 Using tryptophan-deficient and nondeficient synthetic amino acid test diets, Kloppel and Post16 reported that scoliosis was observed in the tryptophan-deficient rainbow fish after 1 week of feeding. Histological studies of scoliotic fish revealed hyperemia, disorganization of myomere septa and protrusions of the fibrous matrix sheath, which invests the notochord. Conditions returned to normal within 1 week upon replacement of tryptophan in the diet. 

In mice fed a tryptophan-deficient diet ad libitum for 1 week, Jones et al.31 reported on tissue serotonin synthesis rates, systemic tryptophan metabolism, and its response to steroid or cycloheximide treatment. In the experimental mice, brain serotonin synthesis was decreased while duodenal serotonin synthesis was increased following a tryptophan load. Liver total protein was depressed in experimental mice but increased following a tryptophan load. Blood tryptophan (total and free) and albumin were decreased in experimental mice, but ratios of albumin-bound tryptophan were increased. Enzyme kinetic studies indicated that, in experimental mice, brain tryptophan-5-hydroxylase had a reduced Vmax but the enzyme response to tryptophan or hydrocortisone injection was increased. However, hepatic tryptophan-2,3-dioxygenase response to tryptophan or hydrocortisone injection was blunted in experimental mice. 

Using broiler chicks fed a control or tryptophan-deficient diet for 2 to 4 weeks, Carew et al.39 reported signs of relative hyperthyroidism in chicks fed the tryptophan-deficient diet compared to pair-fed controls (chicks fed the same quantity of diet as consumed by experimental group). Plasma triiodothyronine (T3) was elevated in the experimental group. 

In animals with experimental cataracts due to being fed a diet deficient in tryptophan, the soluble lens proteins were proportionally reduced.4-6 Rats fed a tryptophan-deficient diet had lower lens dry weight and lens water was increased and P-crystallin was decreased compared to that in normal lenses.40... 

It has been known for many years that diets deficient in tryptophan lead to depletion of brain serotonin and hence to disturbances in serotonin-mediated brain function.41 Subsequently, in the early 1970s, Fernstrom and Wurtman42-43 began a systematic investigation of the relationship between tryptophan supply and serotonin synthesis under a variety of circumstances. The role of tryptophan deficiency on neuropsychiatric conditions is reviewed in Chapter 7. In addition, studies of rapid tryptophan depletion have been conducted on a wide variety of neuropsychiatric conditions in humans and in experimental conditions in animals. This approach and the findings are also reviewed in detail in Chapter 7. 

In the older literature, studies dealing with nutritional deficiencies, including tryptophan deficiency, utilized foodstuffs that were fed ad libitum to animals. It readily became apparent from such experiments that animals offered diets deficient in one of many essential food constituents consumed progressively less food and, thereby, showed increasing evidence of undernutrition. This was in contrast to the control animals, which consumed much food and gained weight. After weeks or months, the experimental and control animals... 

Patrich, H. and Bennington, L. K., Biochemical changes in the rat produced by feeding a tryptophan deficient ration, Proc. West. VA Acad. Sci., 41, 161, 1969. 

Singh, M., Effect of niacin and niacin-tryptophan deficiency on pancreatic acinar cell function in rats in vitro, Am.. Clin. Nutr., 44, 512, 1986. 

Koch, H. R., Ohrloff, C., Bours, J., Riemann, C., Dragomirescu, V., and Llockwin, O., Separation of lens proteins in rats with tryptophan deficiency cataracts,... 

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