Tryptophan Load Test Research Articles

Tryptophan Metabolism in Women Using Steroid Hormones for Ovulation Control

This is an extension of work recently reported by Rose regarding young women using a combination of progesterone and estrogen for ovulation control. The 10 subjects studied had an abnormal xanthurenic acid excretion after a loading dose of tryptophan. After treatment with 2.5 mg norethynodrel and .1 mg mestranol (Enovid-E) from Days 5 to 24 of the the cycle, 24-hour urine specimens were collected before and after administration of 2 gm of L-tryptophan. They were then given 25 mg of pyridoxine hydrochloride 4 times a day during the 48 hours required to repeat the tryptophan loading test. Controls were 18 healthy women not taking drugs. Metabolites of trytophan determined were indican, anthranilic acid glucuronide, 0-aminohippuric acid, kynurenic acid, acetylkynurenine, kynurenine, 3-hydroxykynurenine, xanthurenic acid, and N-methyl-2-pyridone-5-carboxamide. Urine specimines were analyzed for these and for 4-pyridoxic acid taking usual precautions to avoid dietary factors or drugs which might vitiate the results. At first the ingestion of the steroid had no significant effect on the basal excretion of urinary tryptophan metabolites. However, after the loading dose of tryptophan, the subjects taking Enovid E- excreted a mean level of 697 micro-moles of xanthurenic acid compared with a mean level of 29.8 micro-moles in controls. Some of the other metabolites were also excreted in increased quantities: 3-hydroxykynurenine, kynurenine, kynurenic acid, and acetylkynurenine. The others were excreted in normal quantities. When experimental subjects were given 100 mg/day of supplemental pyridoxine hydrochloride, tryptophan metabolism was essentially normal. These results should be considered in human metabolic studies of pyridoxine-requiring enzyme systems.

Enzymatic Determination of Pyridoxal Phosphate in Plasma by Decarboxylation of L-Tyrosine-14 C (U) and a Comparison with the Tryptophan Load Test

Enzymatic Determination of Pyridoxal Phosphate in Plasma by Decarboxylation of L-Tyrosine-14 C (U) and a Comparison with the Tryptophan Load Test

Pyridoxine Deficiency and Tryptophan Metabolism in Chronic Alcoholics

T-Tryptophan oral load tests were administered to twenty-one chronic alcoholic patients and fasting plasma pyridoxal-5-phosphate levels were estimated. Three patients (14 per cent) were thought to be pyridoxine deficient and the data indicated that tryptophan load tests were abnormal with plasma pyridoxal-5-phosphate levels of less than 40 per cent of normal. Nine subjects were considered normal and nine had subnormal urinary excretion of tryptophan-nicotinic acid intermediate metabolites, although plasma pyridoxal-5-phosphate levels in both these groups were more than 40 per cent of normal. Possible explanations of subnormal metabolite excretion are discussed and it is proposed that there may be facilitated tryptophan-nicotinic acid conversion in chronic alcoholism because of increased metabolic requirements for nicotine-adenine dinucleotide (NAD). There was no confirmation of previous reports of reduced 5-hydroxyindole-acetic acid excretion in chronic alcoholic subjects.

Is the tryptophan load test a valid index for a chemically-induced vitamin B6 deficiency?

Is the tryptophan load test a valid index for a chemically-induced vitamin B6 deficiency?

In vivo formation of pyridoxal phosphate schiff's base—an inherent defect in the tryptophan load test

The excretion of xanthurenic acid by four adults following oral administration of up to 7 g (100 mg/kg) tryptophan, increases markedly with the size of the dose. The excretion of xanthurenic acid by adults is much larger than by children given a comparable dose on the basis of body weight. Administration of pyridoxine during the test reduced the excretion by an adult to the level seen in children. A possible interpretation of this is discussed. The results indicate the limits within which the tryptophan load test can be reproduced.

Effect of pyridoxine deficiency on porphyrin precursor excretion in acute intermittent porphyria

Experimental pyridoxine deficiency was induced in a patient with acute intermittent porphyria by means of a synthetic diet and administration of deoxypyridoxine. Determination of urinary excretion of pyridoxic acid, oxalate and xanthurenic acid, and of the total circulating lymphocytes, confirmed the presence of pyridoxine deficiency during the experimental period. The patient was asymptomatic both during and prior to the study, which was terminated after fifteen days due to the development of an optic neuritis. Urinary excretion of Δ-amino-levulinic acid (ALA) and porphobilinogen declined significantly during the period of proved pyridoxine deficiency and increased again following the administration of pyridoxine. Tryptophan loading tests suggested that the patient may have had a relative intracellular pyridoxine deficiency prior to the study. The results are consistent with other evidence that Δ-amino-levulinic acid synthetase is the rate-limiting enzyme in porphyrin biosynthesis in man.

Tryptophan load tests and pyridoxal-5-phosphate levels in epileptic children. I. Non-progressive brain damage and degenerative brain disorders.

Tryptophan load tests and pyridoxal-5-phosphate levels in epileptic children. I. Non-progressive brain damage and degenerative brain disorders.

Tryptophan load tests and pyridoxal-5-phosphate levels in epileptic children. II. Cryptogenic epilepsy.

Tryptophan load tests and pyridoxal-5-phosphate levels in epileptic children. II. Cryptogenic epilepsy.

Excretion of tryptophan metabolites in Friedreich's ataxia.

The overnight urinary excretions of the tryptophan metabolites 5-hydroxy indole acetic acid (5HIAA), indole acetic acid (IAA), indoxyl sulphate, and kynurenine were determined in 10 cases of Friedreich's ataxia and in 11 controls. Levels of 5HIAA and IAA were slightly lower and of indoxyl sulphate higher than in the controls but within normal limits; kynurenine was normal.A tryptophan load test subsequently given to four patients and three controls showed no significant abnormality in IAA, 5HIAA, indoxyl sulphate, and kynurenine.A specific abnormality in tryptophan metabolism in Friedreich's ataxia suggested by other workers was not observed.

Studies of pyridoxal-penicillamine antagonism in the human

The pyridoxal- l-penicillamine antagonism previously studied by others in lower animals has now been studied in man by means of urinary xanthurenic acid (XA) excretion levels. Subjects of the present study, all Chinese, included 21 normal individuals and 2 patients with Wilson's disease. The studies involved urinary XA determinations, with and without tryptophan-loading tests, and with varying dosage combinations of penicillamines and pyridoxine hydrochloride. It was found that urinary XA excretions remained normal after dl-penicillamine or dl-tryptophan alone but increased when the two were taken together; pyridoxine hydrochloride prevented the increase. No increases in urinary XA excretion occurred when d-penicillamine or N-acetyl- dl-penicillamine were used in place of the dl-penicillamine during tryptophan loading. These results support the thesis that a pyridoxal- l-penicillamine antagonism can operate in the human, both in normal individuals and in those with Wilson's disease.

Excretion of tryptophan metabolites in different forms of haemoblastosis

Spontaneous excretion of tryptophan metabolites was followed in 68 patients affected by haemoblastosis. Abnormal levels of kynurenine were found to be excreted by 8 out of 13 subjects with malignant lymphoma, by 8 out of 22 subjects with leukaemia, and by 3 out of 5 cases with multiple myeloma. In all 28 Hodgkin's disease patients examined, kynurenine was excreted consistently above normal levels. Excretion values varied among the patients and were roughly correlated to the severity of the disease. Abnormal amounts of 3-hydroxy-kynurenine and 3-hydroxyanthranilic acid were excreted by a few of the same patients. Administration of vitamin B 6, as pyridoxine hydrochloride or pyridoxal-5-phosphate, In io patients with Hodgkin's disease normalized kynurenine and 3-hydroxykynure-nine excretion whereas it caused a contemporaneous increase of urinary 3-hydroxy-anthranilic acid. The effects of several therapeutic agents on the excretion were also observed. Tryptophan loading tests (50 mg/kg) were performed in n Hodgkin's disease patients: excretion of kynurenine, N-α-acetyl-kynurenine, 3-hydroxykynurenine, kynurenic, xanthurenic, and 3-hydroxyanthranilic acids was determined in comparison with that of 5 normal controls. The total amount of these substances was 3.3 times larger in these patients than in the controls. A week after the first load a second tryptophan test was carried out with contemporaneous administration of 3 large doses of vitamin B 6. Pyridoxine was unable to normalise the patients' excretion. The vitamin acted by increasing the amount of 3-hydroxyanthranilic acid and by decreasing the amounts of the other metabolites.

Recommendations for Standardization of the Tryptophan Load Test

Recommendations for Standardization of the Tryptophan Load Test

DL-penicillamine as a cause of optic axial neuritis.

Severe visual disturbance associated with lesions of the optic nerve developed in a Wilson's disease patient who had been receiving DL-penicillamine therapy for more than 2 years. Prompt relief was achieved with pyridoxine hydrochloride. These results suggest that the optic nerve lesions resulted from a penicillamine-induced pyridoxine deficiency. Furthermore, results of urinary xanthurenic acid excretion studies made on the patient before and after tryptophan loading tests, which were conducted during periods of no therapy, penicillamine therapy, and penicillamine plus pyridoxine therapy, indicate an alteration in pyridoxine metabolism in the presence of penicillamine. Although no other similar cases have been described, the present results indicate the possibility that patients on prolonged high dosage levels of penicillamine may require pyridoxine supplementation of their diet.

Pyridoxine-responsive anemia.

Two patients presented themselves with a hypochromic, microcytic anemia which was responsive to pyridoxine hydrochloride. One also had hemochromatosis and impaired iron utilization. A complete hematological response occurred on 2 occasions in the second patient. Hypochromasia and microcytosis persisted after hemoglobin values had returned to or near normal. A tryptophan-loading test in one case showed that the abnormal levels of hydroxykynurenine were corrected by pyridoxine therapy. The literature on pyridoxine-responsive anemia is reviewed, and it is suggested that a phosphorylating enzyme of pyridoxine may be implicated in this disease.

Paper chromatography of urinary indoles extracted under alkaline and acid conditions

1. A method for the extraction and paper chromatographic analysis of urinary indoles is described which utilizes ethyl ether and 2-butanone sequentially under alkaline and acidic conditions. 2. The advantages of this procedure are two-fold: (1) it permits the fractionation of urinary indoles into multiple extracts with not too much overlapping and (2) it makes possible the paper chromatographic analysis of urine extracts more highly concentrated than heretofore employed. 3. The pattern of excretion of urinary indoles in a total of 50 normal male urines (individual or pooled) as demonstrated by this method is presented. The indoles most generally detected in normal male urines were tryptophan, indican, indoleacetic acid, indoleacetylglutamine, indoleacetylglucuronic acid, indoleacetamide, 5-hydroxy-indoleacetic acid, 6-hydroxyskatole sulfate (in 30 % of normals), and traces of indolelactic acid, and N-acetyltryptophan. 4. The effect of alkaline, acid, and enzymic (β-glucuronidase) hydrolysis of urine prior to extraction was studied. 5. The effect of tryptophan load tests is reported. 6. By utilization of this method, the presence of indoleacetylglucuronic acid was demonstrated in the acid-butanone extract and its relationship to indoleacetamide in the alkaline-ether extract was established. (See A ddendum.)

The Tryptophan Load Test in the Syndrome of Infantile Spasms with Oligophrenia

The Tryptophan Load Test in the Syndrome of Infantile Spasms with Oligophrenia

Indole Metabolism in Mental Illness

Abstract Abnormal indole metabolism, long implicated in mental illness, is well delineated in three diseases having mental symptoms: phenylketonuria, Hartnup (H or Hart's) disease, and pellagra. Recent research suggests that indole metabolism may be disturbed in schizophrenia. The evidence for this is evaluated in terms of: number and effectiveness of indolic psychotogens, effect of indoles on the brain, effect of psychotherapeutic drugs on model psychoses induced by indoles, excretion of urinary indoles before and after tryptophan load tests, animal toxicity tests, urinary glyoxylic acid test, and detection by paper chromatography of abnormal urinary indole production. The indoles reported in human urine are discussed critically with respect to excretion data, metabolic origin, and possible relationship to mental disease. Urinary excretion studies in mental illness must consider such factors as medication, dietary differences, excretion products from intestinal bacteria, eccentric bowel habits, age, muscle mass, sex, physical activity, and adequate normal controls. In various reports, these factors were not well controlled. In some carefully conducted studies, however, abnormal excretion was still detected in schizophrenics, particularly in studies dealing with the glyoxylic acid test and 6-hydroxyskatole sulfate excretion. Despite the controversial aspects, reports of abnormal indole metabolism in mental illness are sufficiently numerous to warrant further studies along the lines indicated above.

The Significance of the Tryptophan Load Test in Infantile Spasms with Oligophrenia

The Significance of the Tryptophan Load Test in Infantile Spasms with Oligophrenia

Pyridoxine-Responsive Anemia: Report of 2 Cases in Brothers and a Review of the Literature

Abstract The clinical and laboratory findings in two brothers with severe anemia are presented. These findings were very similar in both cases. Evidence that at least one of them suffered from a pyridoxine-responsive anemia is presented. It was assumed that the other had the same disorder since, in addition to the striking similarity in the clinical and laboratory abnormalities, the latter’s anemia disappeared completely with the parenteral administration of vitamin B complex, which provided him with 2 mg. of pyridoxine daily. These patients have not relapsed 1.5 and 6 years after stopping the therapy. A review of the reported cases with anemia responding to vitamin B6 administration is presented. Common factors observed in some of these cases are: (1) severe anemia, microcytic and hypochromic in type, chiefly due to a striking maturation erythroblastic arrest at the basophilic stage with no defect in leukocytes or thrombocytes; (2) hyperferremia and hemosiderosis; (3) an abnormal tryptophan-loading test; and (4) complete or almost complete correction of all abnormalities with administration of vitamin B6, even at small doses. These data were considered to suggest that the patients had a true deficiency in pyridoxine. In other patients, no increased excretion of xanthurenic acid has been observed after a tryptophan-loading dose, and pyridoxine administration has improved the anemia only partially and has not reversed the serum iron parameters to normality. All of these other patients suffered from a familial hypochromic anemia not due to iron deficiency or from a "sidero-achrestic" or "refractory normoblastic" anemia. The cause of the disorder in patients in the first group is unknown, but, by exclusion, increased requirement of vitamin B6 seems to be the most likely possibility.

Pyridoxine Deficiency in Hyperthyroidism.

SummaryThe occurrence of pyridoxine deficiency was determined in 14 patients with hyperthyroidism and 14 control euthyroid patients by the tryptophan load test. Urinary xanthurenic acid excretion following the tryptophan load test was significantly greater in hyperthyroid patients than in controls. Mean excretion of xanthurenic acid in hyperthyroid cases was 71.9 mg/24 hr with standard deviation of 56.0. Mean xanthurenic acid excretion of control cases was 15.4 with standard deviation of 6.1. After pyridoxine administration, mean xanthurenic acid excretion was 13.2 with standard deviation of 8.7 in the hyperthyroid cases, while in the control group, xanthurenic acid excretion was 12.5 with standard deviation of 5.2. Since pyridoxine is required for orderly catabolism of tryptophan and pyridoxine corrected this metabolic aberration, it is not unreasonable to state that in hyperthyroidism, the availability of pyridoxine is limited. Until the actual significance of these findings becomes more clearly defined...