Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TRYPTOPHAN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1975

Tryptophan catabolism by tryptophan pyrrolase in rat liver. The effect of tryptophan loads and changes in tryptophan pyrrolase activity.

We investigated how changes in tryptophan pyrrolase activity and tryptophan loads affect the breakdown of tryptophan was estimated by injecting rats with [ring-2-14-C]tryptophan and measuring respiratory 14-CO2. We concluded, contrary to previous reports, that induction of tryptophan pyrrolase definitely will increase the rate of tryptophan breakdown. Tryptophan loads also increase tryptophan breakdown even in circumstances where there is no increase in tryptophan pyrrolase activity, presumably by increasing the saturation of the enzyme. After a tryptophan load (50 mg per kg) the increase in liver tryptophan concentration lasts only 30 min. The rapid return of liver tryptophan to normal may be due partly to the high turnover rate of liver tryptophan. We estimate that tryptophan pyrrolase degrades tryptophan in vivo at a rate that is equivalent to the whole liver tryptophan concentration in 7.5 min or less.

Adrenalectomy↗
PubMed1975

The rate of tryptophan oxidation by tryptophan pyrrolase in the rat: effect of tryptophan loads and changes in tryptophan pyrrolase activity.

The in vivo assay of tryptophan pyrrolase gives best results when [ring-2-14C] tryptophan is used and rates of labelled CO2 production are measured at short times after the labelled tryptophan injection. Using this technique in conjunction with in vitro measurements, we find that both tryptophan pyrrolase activity and the liver tryptophan concentration are important factors in controlling the rate of tryptophan breakdown by pyrrolase. Tryptophan in the liver has a very high turnover rate, and the enzyme activity and the liver tryptophan concentration interact. Thus a high liver tryptophan increases the enzyme to speed tryptophan breakdown, while a high pyrrolase activity may tend to lower liver tryptophan, thus tending to decrease both the rate of tryptophan catabolism and possibly the enzyme activity.

Animals↗
PubMed1982

Tryptophan and tryptophan pyrrolase in haem regulation. The role of lipolysis and direct displacement of serum-protein-bound tryptophan in the opposite effects of administration of endotoxin, morphine, palmitate, salicylate and theophylline on rat liver 5-aminolaevulinate synthase activity and the haem saturation of tryptophan pyrrolase.

1. The increase in the haem saturation of rat liver tryptophan pyrrolase caused by tryptophan administration was previously shown to be associated with a decrease in 5-aminolaevulinate synthase activity. 2. It is now shown that similar reciprocal effects are caused by palmitate and salicylate, both of which increase tryptophan availability to the liver by direct displacement of the serum-protein-bound amino acid. 3. The reciprocal effects on the former two parameters caused by endotoxin and morphine are associated with an increase in liver tryptophan concentration produced by a lipolysis-dependent, non-esterified fatty acid-mediated, displacement of the serum-protein-bound amino acid. 4. All these changes and those caused by another lipolytic agent, theophylline, are prevented by the beta-adrenoceptor-blocking agent propranolol and by the opiate-receptor antagonist naloxone, whose anti-lipolytic nature is demonstrated. 5. High correlation coefficients have been obtained for one or more pairs of the following parameters: serum non-esterified fatty acid concentration, free serum tryptophan concentration, liver tryptophan concentration, liver 5-aminolaevulinate synthase activity, liver holo-(tryptophan pyrrolase) activity and the haem saturation of liver tryptophan pyrrolase. 6. It is suggested that liver tryptophan concentration may play an important role in the regulation of 5-aminolaevulinate synthase synthesis, and that the latter may be subject to control by changes in lipid metabolism and may be influenced by pharmacological agents that affect tryptophan disposition. 7. Preliminary evidence suggests that tryptophan may be bound in the liver and that such a possible binding may control its availability for its hepatic functions.

5-Aminolevulinate Synthetase↗
PubMed1980

The metabolism of L-tryptophan by isolated rat liver cells. Effect of albumin binding and amino acid competition on oxidatin of tryptophan by tryptophan 2,3-dioxygenase.

1. Novel methods, using L-[ring-2-14C]tryptophan, are described for the measurement of tryptophan 2,3-dioxygenase activity and tryptophan accumulation in isolated rat liver cells. 2. The effects of bovine serum albumin, non-esterified fatty acids and neutral amino acids on tryptophan oxidation by hepatocytes and on the partition of tryptophan between free and albumin-bound forms were investigated. 3. Oxidation of physiological concentrations (0.1 mM) of tryptophan was inhibited by approx. 50% in the presence of 2% (w/v) bovine serum albumin; no effects were found at tryptophan concentrations of 0.5 mM and above. 4. Increases in free tryptophan concentrations produced by displacement of 0.1 mM-tryptophan from albumin-binding sites by palmitate resulted in increased flux through tryptophan dioxygenase. 5. Addition of a mixture of neutral amino acids, at plasma concentrations, to hepatocyte incubations had no effect on the rate of tryptophan oxidation. 6. It is concluded that alterations in free tryptophan concentrations consequent to changes in albumin binding may be an important factor in regulating tryptophan uptake and catabolism by the liver. The results are briefly discussed with reference to possible consequences on brain tryptophan metabolism.

Amino Acids↗
PubMed1984

Interactions of tryptophan synthase, tryptophanase, and pyridoxal phosphate with oxindolyl-L-alanine and 2,3-dihydro-L-tryptophan: support for an indolenine intermediate in tryptophan metabolism.

We have examined the interaction of tryptophan synthase and tryptophanase with the tryptophan analogues oxindolyl-L-alanine and 2,3-dihydro-L-tryptophan. Since these analogues have tetrahedral geometry at carbon 3 of the heterocyclic ring, they are structurally similar to the indolenine tautomer of L-tryptophan, a proposed intermediate in reactions of L-tryptophan. Oxindolyl-L-alanine and 2,3-dihydro-L-tryptophan are potent competitive inhibitors of both tryptophan synthase and tryptophanase, with KI values (3-17 microM) 10-100-fold lower than the corresponding Km or KI values for L-tryptophan. Addition of oxindolyl-L-alanine or 2,3-dihydro-L-tryptophan to solutions of the alpha 2 beta 2 complex of tryptophan synthase results in new absorption bands at 480 or 494 nm, respectively, which are ascribed to a quinonoid or alpha-carbanion intermediate. Spectrophotometric titration data give half-saturation values of 5 and 25 microM, which are comparable to the KI values obtained in kinetic experiments. Our finding that both enzymes catalyze incorporation of tritium from 3H2O into oxindolyl-L-alanine is evidence that both enzymes form alpha-carbanion intermediates with oxindolyl-L-alanine. These results support the proposal that the indolenine tautomer of L-tryptophan is an intermediate in reactions catalyzed by both tryptophanase and tryptophan synthase. In addition, we have found that oxindolyl-L-alanine reacts irreversibly with free pyridoxal phosphate to form a covalent adduct.

Alanine↗
PubMed1986

Beta-elimination of indole from L-tryptophan catalyzed by bacterial tryptophan synthase: a comparison between reactions catalyzed by tryptophanase and tryptophan synthase.

Although tryptophan synthase catalyzes a number of pyridoxal phosphate dependent beta-elimination and beta-replacement reactions that are also catalyzed by tryptophanase, a principal and puzzling difference between the two enzymes lies in the apparent inability of tryptophan synthase to catalyze beta-elimination of indole from L-tryptophan. We now demonstrate for the first time that the beta 2 subunit and the alpha 2 beta 2 complex of tryptophan synthase from Escherichia coli and from Salmonella typhimurium do catalyze a slow beta-elimination reaction with L-tryptophan to produce indole, pyruvate, and ammonia. The rate of the reaction is about 10-fold higher in the presence of the alpha subunit. The rate of indole production is increased about 4-fold when the aminoacrylate produced is converted to S-(hydroxyethyl)-L-cysteine by a coupled beta-replacement reaction with beta-mercaptoethanol. The rate of L-tryptophan cleavage is also increased when the indole produced is removed by extraction with toluene or by condensation with D-glyceraldehyde 3-phosphate to form indole-3-glycerol phosphate in a reaction catalyzed by the alpha subunit of tryptophan synthase. The amount of L-tryptophan cleavage is greatest in the presence of both beta-mercaptoethanol and D-glyceraldehyde 3-phosphate, which cause the removal of both products of cleavage. The cleavage reaction is not due to contaminating tryptophanase since the activity is not inhibited by (3R)-2,3-dihydro-L-tryptophan, a specific inhibitor of tryptophanase, but is inhibited by (3S)-2,3-dihydro-L-tryptophan, a specific inhibitor of tryptophan synthase. The cleavage reaction is also inhibited by D-tryptophan, the product of a slow racemization reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Escherichia coli↗
PubMed1999

Liquid concentrates are lower in bioavailable tryptophan than powdered infant formulas, and tryptophan supplementation of formulas increases brain tryptophan and serotonin in rats.

The bioavailability of tryptophan in powdered and/or liquid concentrate forms of milk-based infant formulas was determined by studying rat growth response by using a slope ratio method (food conversion efficiency: weight gain/food consumed vs. tryptophan consumed). A gelatin basal diet formulated to be adequate in all nutrients, except tryptophan (0.03%), for rat growth was supplemented with graded levels of crystalline L-tryptophan (0.02, 0. 04, 0.06, 0.08, 0.10, 0.12 and 0.14%, standard diets) or infant formulas providing 0.04 and 0.08% supplemental tryptophan (test diets). These diets were fed to weanling rats for 2 wk. Tryptophan bioavailabilities of various formulas varied from 83 to 95%, with some of the liquid concentrates having the lowest values. The levels of bioavailable tryptophan in the liquid concentrate forms (9.7-12.6 mg/g protein) and the powdered forms (11.1-13.1 mg/g protein) were considerably lower than those of human milk (17-19 mg/g protein). Supplementation of the liquid concentrates with graded levels of L-tryptophan (0.1, 0.5 and 1.0%) had no effect on protein quality indices, based on rat growth, but resulted in a dose-related increase in the concentrations of tryptophan in the plasma and brain and of serotonin and 5-hydroxyindole-3-acetic acid in the brains of rats. This study supports further research to investigate the influence of tryptophan supplementation of infant formulas, to more closely simulate tryptophan composition of human milk, on tryptophan metabolites and their potential related effects on sleep latency and neurobehavioral developments in infants.

Animals↗
PubMed1986

Isomerization of (3S)-2,3-dihydro-5-fluoro-L-tryptophan and of 5-fluoro-L-tryptophan catalyzed by tryptophan synthase: studies using fluorine-19 nuclear magnetic resonance and difference spectroscopy.

We are exploring the active site and the mechanism of the pyridoxal phosphate dependent reactions of the bacterial tryptophan synthase alpha 2 beta 2 complex by use of substrate analogues and of reaction intermediate analogues. Fluorine-19 nuclear magnetic resonance studies and absorption spectroscopy are used to study the binding and reactions of the D and L isomers of 5-fluorotryptophan, of tryptophan, and of (3S)- and (3R)-2,3-dihydro-5-fluorotryptophan. Tryptophan synthase specifically and tightly binds the 3S diastereoisomer of both 2,3-dihydro-5-fluoro-D-tryptophan and 2,3-dihydro-5-fluoro-L-tryptophan, whereas it binds 5-fluoro-D-tryptophan more tightly than 5-fluoro-L-tryptophan. Unexpectedly, we find that the D and L isomers of 5-fluorotryptophan, of tryptophan, and of (3S)-2,3-dihydro-5-fluorotryptophan are slowly interconverted by isomerization reactions. Since these isomerization reactions are 10(3)-10(5) times slower than the beta-replacement and beta-elimination reactions catalyzed by tryptophan synthase, they have no biochemical significance in vivo. However, the occurrence of these slow reactions does throw some light on the nature of the active site of tryptophan synthase and its requirements for substrate binding. Our results raise the interesting question of whether tryptophan synthase itself serves a catalytic role in these slow reactions or whether the enzyme simply binds the substrate and pyridoxal phosphate stereospecifically and thus promotes the intrinsic catalytic activity of pyridoxal phosphate.

Escherichia coli↗
PubMed1995

Relationship between serum tryptophan and tryptophan metabolite levels after tryptophan ingestion in normal subjects and age-related cataract patients.

1. Cataract is the single major cause of blindness worldwide; however, the reasons for the development of this condition remain unknown. It has been suggested that the essential amino acid tryptophan may be implicated in the aetiology but definitive evidence has been lacking. 2. The serum levels of tryptophan and seven of its metabolites have been measured in both cataract patients and control subjects, after administration of tryptophan, in order to determine the typical response profile and to discover whether differences could be found in tryptophan metabolism in the two groups. 3. Tryptophan, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, 5-hydroxyanthranilic acid, 5-hydroxytryptophan and anthranilic acid were measured by HPLC with dual electrochemical and programmable wavelength fluorescence detection. Fasting cataract patients (n = 42) and control subjects (n = 37) were given an oral dose of L-tryptophan and sera were sampled at 0, 1, 2, 4 and 6 h. 4. Statistically significant differences in the distribution of data between the two groups were observed. The responses of kynurenine and 5-hydroxyanthranilic acid were higher in cataract patients, but those of kynurenic acid and total tryptophan were lower than in control subjects. No statistically significant differences in free tryptophan, anthranilic acid, 3-hydroxyanthranilic acid, xanthurenic acid or 5-hydroxytryptophan levels were noted. 5. We conclude that there is a major subgroup of age-related cataract patients with a dysfunction in the metabolism of tryptophan. This may be related to the onset of cataract. The mechanism remains to be established but may operate via the action of tryptophan metabolites, such as 5-hydroxyanthranilic acid, which become reactive towards protein upon oxidation.

Age Factors↗
PubMed1976

Tryptophan metabolism in the isolated perfused liver of the rat: effects of tryptophan concentration, hydrocortisone and allopurinol on tryptophan pyrrolase activity and kynurenine formation.

1 The effect of tryptophan concentration on the rate of kynurenine appearance and tryptophan disappearance in the medium perfused through the isolated liver of the rat has been investigated. The effect of pretreatment of the rat with hydrocortisone or allopurinol was also examined, together with the effects of these treatments on liver tryptophan pyrrolase activity measured in vitro at the beginning and end of perfusion. 2 Hydrocortisone (5 mg/kg) injection 3 h before perfusion resulted in a four-fold increase in kynurenine production by the liver during perfusion with a medium containing either 0.1 mmol/1 or 1.0 mmol/1 tryptophan. Injection of allopurinol (20 mg/kg) together with hydrocortisone and addition of allopurinol (4 mg/100 ml) to the medium abolished the hydrocortisone-induced rise of kynurenine in the 0.1 mmol/tryptophan medium but not the 1.0 mmol/1 tryptophan medium. 3 Injection of cycloheximide (30 mg/kg) with hydrocortisone (5 mg/kg) 3 h before perfusion inhibited the hydrocortisone-induced rise of kynurenine production and the increase in pyrrolase activity measured in vitro both before and at the end of perfusion with 1.0 mmol/1 tryptophan. This last result suggests that protein synthesis is involved not only in hydrocortisone induction of pyrrolase but also in substrate induction. 4 Kynurenine production in the 1.0 mmol/1 tryptophan medium was less in both saline- and hydrocortisone-treated older rats (335-450 g) compared to younger rats (180-220 g). In agreement with a previous study, pyrrolase activity in vitro was also lower in both saline- and hydrocortisone- treated older rats at the beginning of the perfusion although activity had risen equally in both young and older rats at the end of perfusion. 5 There was little correlation between the rate of tryptophan disappearance from the medium and the activity of tryptophan pyrrolase either as measured in vitro or as indicated by the rate of kynurenine production. 6 In general, the production of kynurenine in the medium at the end of the 60 min perfusion was indicative of in vitro pyrrolase activity at the start of the perfusion. 7 It is concluded that while in vitro pyrrolase assay does not give a quantitative index of kynurenne production, it does provide a qualitative index. Furthermore, if kynurenine production in the isolated perfused liver of the rat is indicative of in vivo pyrrolase activity, then hydrocortisone must induce pyrrolase activity in vivo.

Age Factors↗
PubMed1981

Tryptophan pyrrolase in haem regulation. The mechanism of the opposite effects of tryptophan on rat liver 5-aminolaevulinate synthase activity and the haem saturation of tryptophan pyrrolase.

1. Administration of tryptophan to starved rats causes a rapid decrease in liver 5-aminolaevulinate synthase activity associated with an increase in the haem saturation of tryptophan pyrrolase. Both effects are maximally produced at 30 min by a 100 mg/kg body wt. dose of tryptophan. 2. Pb2+ prevents both effects. 3. Prevention by allopurinol or benserazide of the tryptophan-induced increase in the haem saturation of tryptophan pyrrolase renders this haem available for further repression of synthase synthesis. 4. The opposite effects on synthase activity and pyrrolase saturation with haem caused by administration of 5-aminolaevulinate, but not those by that of haematin, are potentiated by tryptophan. 5. It is suggested that tryptophan decreases 5-aminolaevulinate synthase activity and causes the initial increase in the haem saturation of tryptophan pyrrolase by enhancing the conversion of 5-aminolaevulinate into haem by a process requiring protein synthesis.

5-Aminolevulinate Synthetase↗
PubMed2006

Interactions of tryptophan, tryptophan peptides, and tryptophan alkyl esters at curved membrane interfaces.

Motivated by ongoing efforts to understand the mechanism of membrane protein crystallogenesis and transport in the lipidic cubic phase, the nature of the interaction between tryptophan and the bilayer/aqueous interface of the cubic phase has been investigated. The association was quantified by partitioning measurements that enabled the free energy of interaction to be determined. Temperature-dependent partitioning was used to parse the association free energy change into its enthalpic and entropic components. As has been observed with tryptophan derivatives interacting with glycerophospholipid bilayers in vesicles, tryptophan partitioning in the cubic phase is enthalpy driven. This is in contrast to partitioning into apolar solvents, which exhibits the classic hydrophobic effect whose hallmark is a favorable entropy change. These results with tryptophan are somewhat surprising given the simplicity, homogeneity, and curvature of the interface that prevails in the case of the cubic phase. Nevertheless, the interaction between tryptophan and the mesophase is very slight as revealed by its low partition coefficient. Additional evidence in support of the interaction was obtained by electronic absorption and fluorescence spectroscopy and fluorescence quenching. Partitioning proved insensitive to the lipid composition of the membrane, examined by doping with glycerophospholipids. However, the interaction could be manipulated in meaningful ways by the inclusion in the aqueous medium of salt, glycerol, or urea. The effects seen with tryptophan were amplified rationally when measurements were repeated using tryptophan alkyl esters and with tryptophan peptides of increasing length. These findings are interpreted in the context of the insertion, folding, and function of proteins in membranes.

Esters↗
PubMedDate not supplied

Optimization of tryptophan production in bacteria. Design of a strategy for genetic manipulation of the tryptophan operon for tryptophan flux maximization.

In the present work we have applied the indirect optimization method (Torres, N. V. et al. Biotechnol. Bioeng. 1996, 49, 247-258) to the maximization of tryptophan biosynthesis in Escherichia coli. The optimization procedure is applied to an updated model of this biochemical system (Xiu, Z-L et al., J. Biotechnol. 1997, 58, 125-140) and thus extended to a problem that includes the processes of transcription and translation. The model representation used by these authors is first translated into the corresponding S-system version. Then, to guarantee cell viability, we impose a set of constraints on some variable and parameter values, all of which are able to be modulated by available techniques. Our results show that it is possible to attain a stable and robust steady state with a rate of tryptophan production increased more than 4 times. This is achieved by changing four key parameters related to the efflux of tryptophan, the growth rate, the inhibition constant, and the tryptophan repressor level. Moreover, it is demonstrated that we can reach this optimum state in a sequential manner, each step leading us to a better situation in relation to the previous one. Thus, only by doubling the tryptophan excretion we can triplicate the rate of tryptophan production. A further, although lesser, improvement can be attained by increasing 4-fold the rate of growth and subsequently by weakening the inhibitory feedback interaction of tryptophan on the enzymes leading to its synthesis. Finally, a significant jump in the rate of production can be obtained if the level of the trp operon could be decreased. When a second approach was considered, in which the growth rate is kept constant in the optimized profile, we found out that by modulation of the parameters it is possible to increase more than 2-fold the rate of tryptophan production.

Biotechnology↗
PubMed1995

Characterization of the tryptophan binding site of Escherichia coli tryptophan holorepressor by phosphorescence and optical detection of magnetic resonance of a tryptophan-free mutant.

The L-tryptophan binding site of the Escherichia coli tryptophan holorepressor (trpR) is characterized by low-temperature phosphorescence and optical detection of magnetic resonance (ODMR) spectroscopy. Measurements are made on a tryptophan-free mutant of trpR, W19/99F, in which both intrinsic tryptophan residues of apo-trpR have been replaced with phenylalanine. Thus, essentially all of the phosphorescence that is observed from trpR originates from the bound L-tryptophan corepressor. The phosphorescence and ODMR results for the bound corepressor agree quite well with those obtained previously for the corepressor site in both single tryptophan-containing mutants, W19F and W99F [Burns, L.E., & Maki, A.H. (1994) J. Fluorescence 4, 217-226]. A red shift of the L-tryptophan phosphorescence origin as well as a decrease in the D-E ODMR frequency result from an increase in the local polarizability upon binding at the corepressor binding site. A large decrease in the ODMR line widths signals a reduction of local heterogeneity upon binding. Subsequent binding of trpR to a self-complementary DNA sequence that mimics the trp operator, 5'-CGTACTAGTTAACTAGTACG-3', produces a further decrease in line widths and additional changes in the ODMR frequencies, attributable to an increase in both the D and E parameters. This result demonstrates that binding of holo-trpR to the operator affects the local environment of the bound corepressor.

Bacterial Proteins↗
PubMed1978

The modification of the lone tryptophan residue in human serum albumin by 2-hydroxy-5-nitrobenzyl bromide. Characterization of the modified protein and the binding of L-tryptophan and benzodiazepines to the tryptophan-modified albumin.

The possible function of the lone tryptophan residue of human serum albumin in the stereospecific binding site for indole and benzodiazepine compounds was investigated by chemical modification. This residue can be selectively modified with 2-hydroxy-5-nitrobenzyl bromide. The modification alters the conformation of the albumin only slightly, as revealed by circular dichroism, fluorescence, and ultraviolet absorption measurements. A decrease in the association constants of L-tryptophan and diazepam of about 30 - 50% and a decrease in the extrinsic Cotton effects of four benzodiazepine derivatives of about 10 - 15% were found as specific effects of the tryptophan modification. The tryptophan modification itself did not change the number of binding sites of diazepam and L-tryptophan. It is suggested that the lone tryptophan residue of human serum albumin is not directly involved in the specific binding site for indole and benzodiazepine compounds. However, the modification alters the properties of the binding site either by an incomplete refolding of the albumin after urea treatment, or a more selective allosteric effect of the modified tryptophan residue.

2-Hydroxy-5-nitrobenzyl Bromide↗
PubMed1974

Regulation of tryptophan biosynthesis in Saccharomyces cerevisiae: mode of action of 5-methyl-tryptophan and 5-methyl-tryptophan-sensitive mutants.

In a wild-type strain of Saccharomyces cerevisiae the tryptophan analogue dl-5-methyl-tryptophan (5MT) causes only a slight reduction of the growth rate. Uptake experiments indicate that the limited inhibition is partly due to low levels of 5MT inside the cell. On the other hand, this low concentration of 5MT leads to an increase in the activity of the tryptophan-biosynthetic enzymes. Evidence is presented that suggests that 5MT acts primarily through feedback inhibition of anthranilate synthase, the first enzyme of the pathway. A number of 5MT-sensitive mutants have been isolated, characterized, and assigned to one of the following three classes: class I, strains with altered activity and/or feedback sensitivity of anthranilate synthase; class II, strains with elevated uptake of 5MT; class III, mutants with altered regulation of the tryptophan-biosynthetic enzymes, which do not exhibit increases in activity in the presence of 5MT. This failure to exhibit increased enzyme activities in mutants of class III can also be observed after tryptophan starvation. Two mutants of class III show high sensitivity towards 3-amino-1,2,4-triazole. They can not exhibit derepression of some histidine- and arginine-biosynthetic enzymes under conditions that lead to an increase in these same enzymes in the wild-type strain.

Alcohol Oxidoreductases↗
PubMed1967

Induction by L-tryptophan and an analogue, alpha-methyl-DL-tryptophan, of the enzymes catabolizing L-tryptophan in Pseudomonas.

An investigation was made of the pattern of induction of the enzymes that metabolize l-tryptophan through kynurenic acid (the quinoline pathway) in Pseudomonas fluorescens. The first four enzymes in the pathway were not induced in the same proportions or in the same time courses. This lack of coordinate induction excludes a mechanism of regulation of these enzymes at a single site as proposed in the operon model. The enzymes were induced in a sequential pattern in the order of their position on the pathway, when they became the limiting reactions. The nonmetabolizable analogue, alpha-methyl-dl-tryptophan, caused a measurable elevation in the levels of the first three enzymes of the same pathway. Evidence is presented that growth of the cells in the presence of alpha-methyl-dl-tryptophan caused the accumulation of endogenous tryptophan, and that induction by the nonmetabolizable analogue is induction by the endogenous tryptophan.

Aminohydrolases↗
PubMed1989

Dose-response decrease in plasma tryptophan and in brain tryptophan and serotonin after tryptophan-free amino acid mixtures in rats.

Rats fasted 15 hours were treated p.o. with increasing amounts (660 and 1320 mg/kg body weight) of a mixture containing a fixed proportion of seven essential amino acids (L-phenylalanine 13.6%, L-leucine 6.0%, L-isoleucine 12.1%, L-methionine 12.1%, L-lysine 30.3%, L-threonine 10.6%, L-valine 15.2%) and lacking tryptophan. The mixtures produced a dose-response decrease of free (by 34% after the lower dose and by 58% after the higher dose of the mixture) and total (by 10 and 31%) plasma tryptophan and of brain tryptophan (by 38 and 65%), serotonin (by 17 and 41%) and 5-hydroxyindole acetic acid (by 21 and 49%). The mechanisms of these changes are discussed.

Amino Acids↗