Tryptophan Intake Research Articles

Relationship between tryptophan intake and urinary excretion of 3-hydroxy-kynurenine, 3-hydroxyanthranilic acid, xanthurenic acid and kynurenic acid.

Some metabolites of tryptophan such as 3-hydroxyanthra-nilic acid (3-OHAA), 3-hydroxykynurenine (3-OHKY) and xanthurenic acid (XA) have been suspected of being carcinogenic, and the relationship between bladder cancer and the urinary excretion of these metabolites has been discussed. However, the relationship between the intake of tryptophan and the excretion of these metabolites has not yet been reported. In this work, the urinary excretion of 3-OHAA, 3-OHKY, XA and kynurenic acid (KA) was determined when an experimental diet containing 770 or 850mg/day of tryptophan was given to six normal female human subjects and when 900mg/day of tryptophan was added to the experimental diet. Under the experimental diet, 3-OHAA, 3-OHKY, XA and KA in urine (μmole/day) were 3.57±1.35, 1.95±1.11, 10.11±3.25 and 15.80±2.35, respectively. Under the additional intake of tryptophan, the values increased to 7.07±5.31, 3.90±2.44, 18.85±7.20 and 31.51±7.52, respectively. The averages of excretion were proportional to the tryptophan intake. Mean excretion ratios (%) of 3-OHAA, 3-OHKY, XA and KA Cumoles) to tryptophan intake (μumoles) were 0.086±0.056, 0.053±0.032, 0.245±0.085 and 0.390±0.084, respectively. However, individual differences and daily fluctuations were observed and it was especially remarkable in 3-OHAA in the period of additional tryptophan intake.

Nutritive value of L-, DL- and D-tryptophan in the chick.

The present study was undertaken to determine the nutritive value of L-, DL- and D-tryptophan in chicks. Day-old chicks were fed commercial chick starter ration for one week and then they were given an experimental diet containing zein as a protein source for three weeks. The experimental results were analyzed by a slope ratio technique (weight gain vs. tryptophan intake). The relative biological utilization of DL- and D-tryptophan compared to L-tryptophan was approximately 55 and 15%, respectively. At the end of the experiment, the chicks were sacrificed and the concentration of free tryptophan in plasma was measured. The free tryptophan concentration in plasma corresponded closely with the increment level of tryptophan in diet when there was a normal level of dietary protein. But there was less correspondence when chicks were fed a diet low in protein.

The relationship of tryptophan and albumin in the acute burn patient: preliminary observations

INTRODUCTION ONE of the most significant metabolic derangemerits in the acute burn patient is the sharp decrease in albumin synthesis and reversal of the a lbumin :g lobu l in ratio. This change in albumin heralds the severity of the insult and the catabolic phase, and when the albumin : globulin ratio reverts to normal and increased albumin occurs, the anabolic phase and repair is commenced. It has been demonstrated experimentally that the amino acid tryptophan has a direct influence on the stimulation of albumin synthesis in the liver. Therefore, it was postulated that if the tryptophan intake of the acute burn patient could be adequately supplemented in the diet, then albumin synthesis might be increased and the anabolic phase expedited. In the acute burn, albumin is diminished because of its loss to the interstitial spaces, decreased synthesis by the liver, a negative state of degradation and synthesis and skin losses. It is thought that the skin contains most of the albumin outside of the vascular system. The plasma contains 30-40 per cent of the moveable plasma. Albumin is important to the body and is frequently used by the burn therapist as a prime indicator of inadequate body repair or successful recovery of the burn patient. The chief functions of albumin are: to create homeostasis between the intravascular and extravascular fluids, to carry metals (zinc), ions, amino acids, enzymes and hormones and as a source of nitrogen. Albumin is manufactured in the liver by the hepatocyte at the rate of 12-14 g per day and its half-life is about 20 days. Nutrition is probably Complete amino acids ~ / ~ mi nus tryptophan ( ~ )

The tryptophan requirements of young laying pullets.

Two experiments were conducted with laying pullets between 32 and 47 weeks of age. In each trial 1728 White Leghorn and 1728 cross-bred pullets were used. A series of diets of increasing protein content was offered. Protein quality was identical in all diets and tryptophan was demonstrated to be the most limiting amino acid in the protein mixture used. The daily tryptophan requirement of the individual pullet was estimated, by indirect methods, to be 2.25 mg/g egg output plus 10.25 mg/kg body weight. Response curves for flocks of pullets are illustrated. Calculated optimum intakes of tryptophan for various ratios of costs of input to value of output are tabulated. It is estimated that for a flock of mean body weight 1.5 kg, producing 55 g egg mass/hen d and consuming 110 g food/hen d, the optimum dietary tryptophan concentration is 1.7 g/kg when the marginal cost of supplying 1 kg tryptophan is 20 times the marginal value of 1 kg egg output.

METABOLIC ABNORMALITIES OF TRYPTOPHAN AND NICOTINIC ACID IN PATIENTS WITH RHEUMATOID ARTHRITIS

The mean plasma total tryptophan concentration of 13 long-standing rheumatoid arthritis patients was found to be lower than that of seven nonrheumatoid control subjects, but the plasma nicotinic acid concentration was unchanged. In the rheumatoid patients the urinary excretion of the tryptophan metabolites, kynurenine, xanthurenic acid and 3-hydroxyanthranilic acid, was increased several fold, but the excretion of N-methylnicotinamide was normal. These findings are discussed in relationship to the dietary intakes of tryptophan, nicotinic acid and pyridoxine, the effect of antirheumatoid drugs on plasma tryptophan and liver tryptophan pyrrolase, and requirement of rheumatoid patients for pyridoxine.

Elevation of plasma glucose and glucagon after tryptophan ingestion in man

To evaluate the effect of tryptophan on blood sugar in man, we have orally administered 10 g of this amino acid to 14 normal subjects and determined their plasma levels of glucose, insulin, glucagon, and growth hormone for 4 hr after the load. Seven of the subjects also received a placebo. Tryptophan intake was followed by a slight but significant elevation of glycemia (maximum increment: 11% above basal values at 180 min, p = 0.02). This elevation of plasma glucose was accompanied by a clear rise of glucagon levels (peak: 60% at 140 min, p = 0.0007) and by increased concentrations of circulating insulin and growth hormone. Placebo administration did not significantly modify blood glucose or any of the hormones measured. In contrast to the reported hypoglycemic effect of tryptophan in rats, our data indicate that this amino acid increases plasma glucose in man. Given that tryptophan appears to possess the capability of eliciting glucagon secretion, its effect on blood glucose can be reasonably attributed to an enhanced glycogenolysis and/or gluconeogenesis provoked by its release of this hormone.

Effect of Antibiotics on Growth of the Immature Rat

The purpose of this study was to quantify the growth promoting effect of a mixture of antibiotics for rats eating diets deficient in protein or an essential amino acid. Male albino weanling rats (70 to 80 g weight, 4 weeks old) were fed (a) a control diet containing all other required nutrients and varying amounts of casein (0 to 27%), or (b) a purified amino acid diet containing all other required nutrients and varying amounts of valine (0 to 70 mumoles/g diet), threonine (0 to 69 mumoles/g diet) or tryptophan (0 to 8.6 mumoles/g diet), with and without an oral antibiotic supplement consisting of neomycin sulfate (10 mg/100 g body weight/day), bacitracin (500 units/100 g body weight/day), and polymyxin B sulfate (1 mg/100 g body weight/day). At suboptimal intake of casein, valine, tryptophan or threonine, rats eating antibiotic-enriched diet showed up to 3 times greater daily body weight gain (deltaBW) than rats eating a similar diet without antibiotics. The growth-promoting effect of antibiotics can be expressed as percent sparing of specified nutrient (casein or individual amino acid), defined as below: (see journal) where nutrient intakeO ab or nutrient intakeab represents that intake of casein or of a particular amino acid which is required to produce a specific deltaBW in antibiotic-free or antibiotic-supplemented group, respectively. The percent sparing was inversely proportional to the dietary content of casein or limiting amino acid. For diets containing 10% to 25%, 25% to 50%, 50% to 75%, and 75% to 100% of the daily requirement of the limiting nitrogenous nutrient, sparing on the average was greater than 80%, 60%, 20%, and less than 10%, respectively. Data on daily food intake of ad libitum fed rats, and data from an experiment with tube-fed rats, showed that the growth-enhancing effect of antibiotics was independent of changes in food intake.

A rapid and sensitive auxin binding system for detecting N6-substituted adenines, and some urea and thiourea derivatives, that show cytokinin activity in cell division tests.

A selective, sensitive and rapid (2 min or less) method for detecting compounds with potential for cytokinin activity is described. The method does not measure cytokinesis; instead, it determines the ability of cytokinin-active agents to (i) activate the intake of either L-tryptophan or indoleacetic acid by germinated spores of the water-mould Achlya, while inhibiting the energy-dependent transport of all L-amino acids usually found in proteins; (ii) inhibit the energy-dependent transport of nucleosides and sugars by the same organism. The compounds with cytokinin activity generally activate auxin (tryptophan) intake at 10(-8) M or greater and inhibit at 10(-6) M or greater. The most effective activating compounds were N6-(delta2-isopentenyl)adenine, N6-benzyladenine. N6-furfuryladenine, and N6-(trans-hydroxy-3-methyl-but-2-enyl)adenine. These compounds are classed generally as cytokinins in plant growth studies. A cell membrane - localized glycopeptide of molecular weight 6000 was isolated from this organism and shown to be the site at which cytokinins, auxin, and tryptophan bind. An earlier study had also established that calcium ions bind to this entity as well. Tryptophan binding to the glycopeptide was enhanced by cytokinins, suggesting that this may be the way in which whole cells display enhanced tryptophan binding in the bioassay. On the other hand, calcium binding was antagonized by cytokinin. The results suggest that this may be an important experimental system for use in studying one possible way in which cytokinin may regulate plant growth.

Plasma and Tissue Tryptophan Levels in Relation to Tryptophan Requirements of Weanling and Adult Rats

Weanling and adult male rats were fed for 9 days diets containing amino acid mixtures providing between 0 and 0.33% of tryptophan in the diet, and were killed either at 2200 (absorptive phase) or at 1100 hours (postabsorptive phase). The weanling rats gained weight maximally (6.7 g/day) when the diet provided 0.14% or more of tryptophan. The adult rats maintained weight at 0.05% tryptophan and gained weight slowly up to 0.09% tryptophan. Plasma tryptophan levels in the young rats rose sharply above an intake of 0.11% tryptophan, the response being more pronounced when samples were taken during the absorptive phase. Adult rats killed in the absorptive state and receiving intakes of 0.04% or more of tryptophan showed a similar though less pronounced inflection in plasma tryptophan concentration. Free tryptophan levels in muscle bore no relationship to dietary tryptophan content, but at all levels of tryptophan intake they increased during the absorptive phase after meals, probably due to insulin release following absorption of carbohydrate from the diet. The tryptophan oxygenase activity in the livers of the adult rats was greater when tryptophan intake exceeded requirements. This increase was obtained only in rats killed during the absorptive phase, and in consequence a diurnal rhythm in enzyme activity was observed in rats receiving adequate but not suboptimal intakes of tryptophan. We conclude that the rate of catabolism of tryptophan absorbed from a meal is determined by a hepatic mechanism monitoring the amount of tryptophan absorbed in relation to the tryptophan status of the body as a whole.

Plasma Tryptophan Response Curve and Its Relation to Tryptophan Requirements in Young Adult Men

A total of 17 adult human subjects was studied to determine the relationships between the concentration of free tryptophan in fasting and postprandial blood plasma, dietary tryptophan intake, and the daily requirement for this amino acid. The diet, containing an L-amino acid mixture, which was patterned as in egg protein, furnished nitrogen equivalent to 0.5 g egg protein per kilogram body weight/day. In two separate experiments dietary tryptophan intake was varied over a range of 1.0 to 8.7 mg/kilogram body weight. Plasma tryptophan concentration was constant above and below tryptophan intakes of 5 and 3 mg/kilogram body weight, respectively, and changed linearly with altered tryptophan intake within this range. The level of dietary tryptophan above which a linear increase in plasma tryptophan occurred was taken to be the requirement level. Nitrogen balance measurements indicated a tryptophan requirement of 2 to 2.6 mg/kilogram body weight whereas the plasma tryptophan data suggested a requirement of about 3 mg/kilogram body weight. The present nitrogen balance data, which did not include integumental and sweat nitrogen losses, probably underestimated tryptophan needs.

Daily Fluctuation of Plasma Amino Acid Levels in Adult Men: Effect of Dietary Tryptophan Intake and Distribution of Meals

Daily Fluctuation of Plasma Amino Acid Levels in Adult Men: Effect of Dietary Tryptophan Intake and Distribution of Meals

Evidence for a Linear Correlation between the Level of Dietary Tryptophan and Hepatic NAD Concentration and for a Systematic Variation in Tissue NAD Concentration in the Mouse and the Rat

The purpose of the study was to determine the relationship of tryptophan intake (substrate availability) and tryptophan oxygenase (TO) activity to formation of nicotinamide adenine dinucleotide (NAD). Mice, both normal and adrenalectomized, and young rats were maintained on a 6 AM to 6 PM light, 6 PM to 6 AM dark schedule and fed ad libitum a synthetic amino acid diet containing various amounts of tryptophan, from zero to about three times the normal requirement for growth. Tissue free tryptophan, TO activity, and tissue NAD were measured. The animals displayed a positive linear correlation between level of dietary tryptophan and hepatic NAD concentration which was most evident during the dark period. There was some indication of a direct relationship between NAD values and tryptophan oxygenase activity at night. These results suggest that increases in enzyme activity may be necessary at the time of feeding in order to achieve the elevated levels of NAD occasioned by intakes of dietary tryptophan which are in excess of that needed for growth. Additional findings indicate the existence of a systematic variation in liver, heart and spleen NAD concentration and in hepatic NAD/NADH ratio.

Tryptophan Intake, Spacing of Meals, and Diurnal Fluctuations of Plasma Tryptophan in Men

The influence of adequate and low tryptophan intakes and the spacing of meals on the concentration of tryptophan in blood plasma of normal adult men was examined. For both levels of dietary tryptophan, when four meals were given daily, at 8:00 AM, 12:00 noon, 4:00 PM, and 9:00 PM, the plasma tryptophan level rose between 1:00 AM and 8:00 AM and decreased between 8:00 AM and 12:00 noon. Plasma tryptophan concentration did not increase in the early morning hours when six meals were offered at 4-hr intervals throughout the day.

Effect of Levels of Nitrogen Intake on Tryptophan Metabolism and Requirement for Pregnancy of the Rat

Investigations were performed to determine the effect of levels of dietary nitrogen on the requirement of tryptophan for pregnancy and on the conversion of tryptophan to N1-methylnicotinamide and to hepatic pyridine nucleotide. Niacin-free diets varying in tryptophan content from 0.03 to 0.13% and in nitrogen content from 0.3 to 3% were fed to pregnant rats for 3 weeks and to nonpregnant rate for 8 weeks. One series of diets contained crystalline amino acids as the only source of nitrogen. Another series contained casein as the source of tryptophan and either tryptophan-free proteins or equinitrogenous amounts of diammonium citrate, glycine and glutamic acid as sources of additional nitrogen. With both series of diets, augmentation of dietary nitrogen induced a lowering of N1-methylnicotinamide excretion. The extent of the lowering of the hepatic pyridine nucleotide levels resulting from increased dietary nitrogen depended on the magnitude of the increase and the duration of the feeding period. Changes from the 1% to the 2% level of dietary nitrogen had an adverse effect on the condition and viability of fetuses of rats fed the 0.09 and 0.07% tryptophan diets but appeared to have no such effect at the 0.13 and 0.11% levels of tryptophan intake.

Some Aspects of Tryptophan and Niacin Metabolism in Young Women Consuming a Low Tryptophan Diet Supplemented with Niacin

The metabolic use of supplements of niacin was studied in 6 college women transferred from a nutritionally adequate control diet of ordinary foods to a semipurified diet low in tryptophan and niacin. Criteria of evaluation were nitrogen balance, blood pyridine nucleotide levels, and urinary excretion of 6 tryptophan and 2 niacin metabolites. Nitrogen loss occurred with a tryptophan intake of 25 mg; nitrogen storage occurred on intakes of 160 or 185 mg. Niacin supplementation had no apparent effect on the amounts of nitrogen excreted. Conversely, the amount of nitrogen excreted did not correlate with metabolite excretion. Blood pyridine nucleotide levels decreased following the second period in which the diet was limiting in tryptophan and niacin, and 10 mg of niacin in the presence of 160 mg tryptophan re-established control levels. Additional niacin did not increase values further. The excretion of tryptophan metabolites tended to respond to the level of the tryptophan ingested, decreasing when tryptophan was limiting and increasing slightly when the tryptophan intake was increased. Niacin supplementation had no apparent effect on tryptophan metabolite excretion. Under these experimental conditions it appears that supplements of niacin added to a diet containing tryptophan at a level just sufficient to establish and maintain nitrogen balance are used first to establish and maintain the levels of the blood pyridine nucleotides and only then is there an increase in the excretion of urinary niacin metabolites.

Biochemical correlates of behavior in schizophrenic patients. Schizophrenic patients receiving tryptophan and methionine or methionine together with a monoamine oxidase inhibitor.

IN THE FIRST part of this longitudinal study, 3,6 a reduced intake of methionine and tryptophan failed to affect schizophrenic behavior conclusively. During this period of seven months of continuously controlled tryptophan intake we found that increases of urinary indoles occurred independently of tryptophan intake when schizophrenic symptoms in some of the patients grew worse spontaneously. The excretions of catecholamines 34 and urinary steroid hormones 28 were also elevated with accompanying motor hyperactivity, increased tension and anxiety. The objective of the second part of this investigation was to study the behavioral responses to increases of methionine and tryptophan as well as that of methionine given together with a monoamine oxidase inhibitor (MAOI). Both improvement and worsening of behavior have been reported for normal, schizophrenic, and depressed subjects. 9,14,27,32 It appeared, therefore, of interest to study urinary excretion patterns in relation to amino acid intake and accompanying

Amino Acid Balance and Nitrogen Retention in Man as Related to Prior Protein Nutriture

A series of experiments was carried out with male college students to determine the influence of prior protein nutriture on the utilization of high N-low tryptophan diets. There was an inverse relationship between prior protein nutriture and the subsequent utilization of the high N-low tryptophan diet. When subjects consumed a balanced, high protein diet they were in strong positive N balance, which, when followed by the high N-low tryptophan diet, led to little N retention. When the initial protein intake consisted of a low level of hydrolyzed casein, supplemented with adequate tryptophan, the initial N balance was essentally zero; during the intake of the high N-low tryptophan diet, the subjects were in greater positive N balance than previously noted following intake of the balanced, high protein diet. When, during a third experiment, the initial period consisted of a low protein intake coupled with an inadequate intake of tryptophan, the subjects were in strong positive balance during the subsequent ingestion of the high N-low tryptophan diet. When, during a fourth experiment, the subjects were immediately given the high N-low tryptophan diet, they were in severe negative N balance. Significant differences in urinary creatinine excretion were observed in some experiments, with no consistent pattern relative to N intake. The variations in urinary creatinine as well as the changes from normal observed in plasma urea N and amino acid N suggest that in young adults there are marked differences in the ultilization of high N diets inadequate in one or more amino acid which, in immature animals, would bring about depressed growth. Changing the N source used to supplement hydrolyzed casein from gelatin to an isonitrogenous mixture of nonessential amino acids did not change the results obtained with the imbalanced diet.

VARIATIONS OF URINARY CREATININE AND ITS CORRELATION TO TRYPTAMINE EXCRETION IN SCHIZOPHRENIC PATIENTS.

IN the course of investigating the effect of diet 011 behaviour and excretion of urinary constituents in schizophrenic patients a remarkably wide variation in the daily output of creatinine was found in several subjects. We also observed a high degree of correlation between the excretion of creatinine and urinary tryptamine. Both phenomena are shown in Fig. 1, where the daily excretions of creatinine and tryptamine along with urine volume and daily tryptophan intake are plotted over 18 consecutive days for the patient who showed the greatest association of these two variables. During the period of observation the creatinine excretion varied from 0.90 to 1.78 g/24 h with a corresponding range of tryptamine excretion of 45–182 µg/24 h. The correlation coefficients between urinary tryptamine and creatinine as well as that of tryptophan intake are presented in Table 1. Both Fig. 1 and Table 1 show that the variations of tryptamine in the urine are not related to the tryptophan intake, which was maintained between 0.53 and 1.04 g/24 h. A highly significant positive correlation is, however, associated with the excretions of tryptamine and creatinine. During the observation period, the patient received a standardized diet containing 1.0–1.5 g of tryptophan/24 h. Exact records were kept of uneaten food and the actual daily intake of each major food constituent calculated by difference. The same standardized diet was given for two months prior to the collection period in order to stabilize the tryptamine excretion in regard to tryptophan intake. No psychotropic medication had been given during 8 months previous to the experiment.

Amino Acid Balance in the Adult: High Nitrogen — Low Tryptophan Diets

Studies were carried out with adult roosters and with male college students to ascertain the influence of increasing the nitrogen (N) intake of diets suboptimal with respect to an essential amino acid (tryptophan), on N utilization. In experiments with adult male chickens, N retention was either the same or greater when the total amino acid intake was doubled, whereas the level of tryptophan remained unchanged and suboptimal. In one study with human subjects, doubling the N intake, while tryptophan remained suboptimal, resulted in a significant increase in N retention, when the period during which the N intake was doubled followed a period of negative N balance. In a second experiment, the high N — low tryptophan diet was given immediately following a period of strong N retention. In this instance, subjects remained in N equilibrium; they did not retain as much N as they had done previously. In contrast with studies with growing rats and chicks, in all experiments with adult chickens or man, no impaired retention of N as a result of increasing the N intake without a concomitant increase in the limiting amino acid was observed. A tryptophan intake of 200 mg/day was found to adequately meet the requirements of the nine subjects studied in these experiments.

Metabolic Patterns in Preadolescent Children: VII. Intake of Niacin and Tryptophan and Excretion of Niacin or Tryptophan Metabolites

Metabolic Patterns in Preadolescent Children: VII. Intake of Niacin and Tryptophan and Excretion of Niacin or Tryptophan Metabolites