Disturbance Of Tryptophan Metabolism Research Articles

Disturbances of tryptophan metabolism in mice acutely deprived of tryptophan.

The effect of a dietary tryptophan deficiency on tissue serotonin (5-hydroxytryptamine) synthesis rates, systemic tryptophan metabolism and its response to steroid or cycloheximide treatment was investigated. Brain serotonin synthesis was depressed in tryptophan-deprived (TD) mice while duodenal serotonin synthesis was enhanced following a tryptophan load. Liver total protein content was initially depressed in TD mice but increased following a tryptophan load. Blood tryptophan and albumin were depressed in TD mice while the percentage of albumin-bound tryptophan significantly increased in TD mice. Serum-free fatty acids were not significantly altered. Furthermore, enzyme kinetics studies indicated that in TD mice, tryptophan-5-hydroxylase has a reduced Vmax, while the Km for both tryptophan and the pteridine cofactor was significantly lowered. The tryptophan hydroxylase response to tryptophan or hydrocortisone injection was accentuated in TD mice while the tryptophan-2,3-dioxygenase response to tryptophan or hydrocortisone injection was blunted in TD mice. Finally, injection of tryptophan and cycloheximide blocked the tryptophan-2,3-dioxygenase response while the tryptophan hydroxylase response was unaltered in both control and TD diet mice.

Disturbances in Tryptophan Metabolism in Rats Following Chronic Dietary Aflatoxin Treatment

Male Holtzman rats were fed 7.8 ppm mixed aflatoxins (AFT) for a 21-week period. At sacrifice there was extensive bile ductule cell proliferation and numerous precancerous changes evident in AFT-treated animals. The in vitro activity of hepatic holo-enzyme tryptophan 2, 3-dioxygenase was reduced in AFT-treated animals which correlated with a reduced urinary excretion of both kynurenine and kynurenic acid suggesting that this reduced tryptophan 2, 3-dioxygenase observed in vitro may be relevant to the in vivo response. The levels of serotonin and 5-hydroxyindole-3-acetic acid were found to be reduced in the pineal, pituitary, various brain regions and in duodenum of AFT-treated rats. It is proposed that the decreased levels of serotonin and 5-hydroxyindole-3-acetic acid in all tissues may be due to either a decreased free tryptophan pool or alterations in 5-hydroxyindole biosynthesis.

Influence of unilateral ECT on tryptophan metabolism in endogenous depression.

Thirteen patients with endogenous depression received an oral load of L-tryptophan (100 mg/kg) before and after a series of unilateral ECT. Age-matched and sex-matched controls also received the tryptophan load twice, at intervals corresponding to those used in the patients. After the loads the level of tryptophan in serum was lower in patients than in control subjects. ECT failed to influence either baseline or postload tryptophan levels. The results are consistent with the notion of disturbances in tryptophan metabolism in patients with endogenous depression, but they fail to clarify the mechanism responsible for the antidepressant effect of ECT.

Multicompartmental analysis of amino acids: III. Tyrosine in affective disorder

Multicompartmental studies of tyrosine in patients suffering from affective disorders and controls gave estimates of 2 major pools of amino acid, together with the associated fractional clearance rates and fluxes. The 2 pools were considered provisionally to represent extracellular and intracellular tyrosine. The concentration of tyrosine in plasma (representing the extracellular pool) and fractional clearance rates from this compartment were normal in ill and recovered patients. The observed abnormalities were confined to the intracellular compartment and consisted of low concentrations of tyrosine in both depressed and recovered patients. In addition, fractional clearance rates from the intracellular compartment were raised in the depressed patients but had returned to normal after recovery. A comparison of these data with those of a similar study of tryptophan described previously suggested that alterations in compartmental volume or dietary differences could not explain the 2 sets of findings. The disturbances in tryptophan metabolism in unipolar affective disorder had led to reduced amounts of this amino acid in the extracellular space. In contrast, the concentration of tyrosine in this compartment was normal, presumably as a result of a metabolic adjustment to the lower amounts found in the intracellular pool. The presence of illness-dependent and illness-independent alterations in tyrosine metabolism in unipolar affective disorder, together with the earlier findings for tryptophan, may have a bearing on the aetiology of the illness.

Disturbance of tryptophan metabolism and its correction during oestrogen treatment in postmenopausal women

A relative pyridoxine deficiency was found in all of 12 women using conjugated oestrogens unopposed by progestagens. This was due to disturbed tryptophan metabolism, expressed in increased xanthurenic acid (XA) excretion (⩾60 μmol/8 h) during 8 h following oral administration of 2 g L-tryptophan. The intake of synthetic oestrogens such as ethinyl oestradiol has already been found to lead to a disturbance of tryptophan metabolism and to a deficiency of vitamin B6. Now we have evidence that this is the case not only in women taking oestrogens in oral contraceptives but also as replacement therapy during the postmenopause. This disturbance is clear after 1 yr of oestrogen treatment. Xanthurenic acid excretion was only slightly increased in 3 women who used progestagens in high dosages at the same time. The biochemical changes induced could easily be corrected by administration of vitamin B6. Our cyclic treatment regimen now consists of 25 days of oestrogens per month. In the remaining days a 250 mg tablet per day of vitamin B6 is prescribed.

Influence of Riboflavin on Disturbances in Tryptophan Metabolism and Hepatoma Production After a Single Dose of Aflatoxin B 1

Female Wistar rats were given a single oral dose of aflatoxin B1, either alone or with a large amount of riboflavin. Biochemical and histologic studies were performed for 30 months. Nine animals of 19 in the aflatoxin-treated group and only 5 of 18 in the riboflavin-aflatoxin-treated group developed hepatomas. The number of rats was insufficient for tests of statistical significance to be fruitful. Urinary excretion of tryptophan metabolites was studied in aflatoxin- and riboflavin-treated rats after an oral administration of 10 mg tryptophan/100 g rat. Riboflavin did not affect the percentage of aflatoxin-treated animals with abnormal urinary excretion patterns, but did increase the magnitude of the disturbances in elimination of kynurenic and xanthurenic acids. The hepatic tryptophan-oxygenase activity was increased only in the two groups given riboflavin, and the levels of nucleic acids were the same in all groups.

Distrubances in tryptophan metabolism after a single dose of aflatoxin B1 and chronic intoxication with carbon tetrachloride.

Distrubances in tryptophan metabolism after a single dose of aflatoxin B1 and chronic intoxication with carbon tetrachloride.

Vitamin B6 metabolism in women using oral contraceptives

Vitamin-B6 metabolism in women using oral contraceptives and who were also receiving a constant diet of known Vitamin-B6 content was evaluated. Subjects were 3 women using oral contraceptives and 2 who were not (age range 22-31 years). Each was fed a diet containing 1.9 mg of Vitamin-B6 daily for 11 days during which time they carried out their normal activities. On Days 3 or 4 7 and 10 a test dose of 2 gm of L-tryptophan was given. Following the tryptophan dose a 24-hour urine specimen was collected and metabolites were determined. Column chromatography and other methods were used to determine metabolites. Vitamin-B6 was determined by microbiological assay. The blood levels of Vitamin-B6 were only slightly altered. The disturbed tryptophan metabolism in each experimental subject was accompanied by a decreased excretion of Vitamin-B6 in urine by 31-38% less than that of the control subjects. This decrease was not related to the length of time the subject had been taking oral contraceptives. Urinary excretion of 4-pyridoxic acid was unchanged. The time of day the subjects had been given the tryptophan test dose modified the metabolism of the oral contraceptive users but not the nonusers. When oral contraceptives were discontinued for the menses interval excretion of tryptophan metabolites was unaffected.

Disturbance of tryptophan metabolism and its correction during hormonal contraception

A relative pyridoxine deficiency was found in 80 % of 100 women using oral contraceptives. This was due to disturbed tryptophan metabolism, expressed in increased xanthurenic acid (XA) excretion ( ≥ 60 μ mol 8 h ) during 8 hours following oral administration of 2 g L-tryptophan. These contraceptives contained a combination of oestrogens and progestogens. Normalization of the excretion was nearly always achieved by giving a large dose of pyridoxine hydrochloride (vitamin B6) ( 100 mg 24 h for 4 weeks). A previously normal XA excretion always showed a significant decrease after treatment with pyridoxine hydrochloride. The blood vitamin B6 concentration is not affected by the use of oral contraceptives or intramuscular medroxyprogesterone acetate (MPA) injections (150 mg every 12 weeks). In the literature, the synthetic oestrogens are regarded as responsible for the disturbance in tryptophan metabolism. The progestogen component of the combined oral contraceptives was found to exert an influence on maximum XA excretion. This could be explained by the intrinsically oestrogenic and anti-oestrogenic properties of the progestogens used. Relative pyridoxine deficiency due to disturbed tryptophan metabolism was found also in 5 out of 15 women who used MPA as contraceptive agent.

Dietary production of myocardial fibrosis in the rat

The dietary production of a cardiomyopathy in rats is described. The tryptophan contents of the diet and plasma were low. Late supplementation with tryptophan, nicotinamide, or pyridoxine failed to prevent fibrosis, and possible reasons for the failure are discussed. Plasma levels of tryptophan correlated inversely with the severity of the cardiomyopathy. The severity of cardiac findings in females was associated with pregnancy rate. A possible relationship to African cardiomyopathy and a significance to cardiac disorders which are associated with disturbances of tryptophan metabolism is suggested.

The nature of the disturbance of tryptophan metabolism in phenylktonuria

The nature of the disturbance of tryptophan metabolism in phenylktonuria

MANAGEMENT OF CARCINOID SYNDROME.

IT HAS BEEN little more than 75 years since carcinoid was first recognized1,2,3and prior to 1939 no case of carcinoid was properly diagnosed preoperatively.4During the past five years increasing information has resulted in frequent recognition and successful treatment of this malignant tumor. What was considered a short time ago to be a rare and peculiar tumor is rapidly gaining prominence in both clinical practice and medical literature. The carcinoid syndrome first described by Thomson5in 1954 accompanies only a small fraction of carcinoid tumors and yet it has become so commonly recognized today that one wonders what became of such patients prior to 1954. The disturbed tryptophan metabolism associated with carcinoid tumors has been elaborated and repeatedly reported and while it is not entirely understood, many facts about it and its relationship to clinical symptoms have been established. Since Lembeck6first reported the presence

A disturbance of tryptophan metabolism in congenital hypoplastic anaemia.

THE clinical entity originally designated as congenital hypoplastic anaemia1 and more recently termed erythrogenesis imperfecta2 is a rare type of anaemia characterized by an erythroid hypoplasia of the bone marrow, by normocytic and normochromic circulating red cells, and by the lack of response to any of the known erythropoietic agents. In the course of some metabolic studies conducted on one such patient whose anaemia was diagnosed shortly after birth and who had been studied for four years by one of the authors (G. M.), a strongly bluishfluorescent substance was noted in the urine. (This patient has been studied through the kindness of Dr. C. P. Katsampes.) This fluorescent material was identified as anthranilic acid by chromatographic methods3, isolation from the patient's urine, and by spectroscopic techniques. The R F of this fluorescent material was 0.90 in butanol : acetic acid : water, 1 : 1 : 5, in agreement with the R F of a known sample of anthranilic acid. The melting point of the material isolated (144–146°) and the absorption spectrum are identical with comparable data reported in the literature for anthranilic acid.