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PubMed1979

Enhancement of rat brain tryptophan metabolism by chronic ethanol administration and possible involvement of decreased liver tryptophan pyrrolase activity.

1. Chronic ethanol administration enhances rat brain 5-hydroxytryptamine synthesis by increasing the availability of circulating tryptophan to the brain. This increased availability is not insulin-mediated or lipolysis-dependent. 2. Under these conditions, tryptophan accumulates in the liver and apo-(tryptophan pyrrolase) activity is completely abolished, but could be restored by administration of regenerators of liver NAD+ and/or NADP+. 3. All four regenerators used (fructose, Methylene Blue, phenazine methosulphate and sodium pyruvate) prevented the ethanol-induced increase in liver tryptophan concentration and the increased availability of tryptophan to the brain. 4. It is suggested that the enhancement of brain tryptophan metabolism by chronic ethanol administration is caused by the decreased hepatic tryptophan pyrrolase activity. The results are briefly discussed in relation to previous work with ethanol. 5. Fructose enhances the conversion of tryptophan into 5-hydroxyindol-3-ylacetic acid in brains of ethanol-treated rats, whereas Methylene Blue inhibits this conversion in both control and ethanol-treated animals.

Animals↗

PubMed1981

Interaction between the oxygen and tryptophan dependence of synaptosomal tryptophan hydroxylase.

The substrate dependence of tryptophan hydroxylase activity in rat striatal synaptosomes was examined. The Km for tryptophan in air to 8--13 microM, comparable to the concentration present in cerebrospinal fluid. The reaction is inhibited by amino acids with large nonpolar side chains. For leucine the inhibition appears competitive; it results from a decrease in the steady state levels of intrasynaptosomal tryptophan. The oxygen Km at 10 microM-tryptophan is 3--4 mm Hg, which is increased when the reaction is assayed with low levels of tryptophan in the medium, and in the presence of amino acids such as leucine. Similarly, the tryptophan Km is increased at low oxygen tensions; at 9 mm Hg of oxygen it is 23 microM. These interactions between tryptophan and oxygen dependence of the reaction are discussed in terms of likely physiological significance and implications for the pharmacological use of tryptophan.

Animals↗

PubMed1976

[Effect of excess D,L-tryptophan on the level of aminoacylation of tRNA by 14C-tryptophan].

The effect of the D,L-tryptophan excess in the rat organism was studied as applied to the level of amino acylation of tRNA by 14C-tryptophan. It is established that the introduction of tryptophan for three days in doses of 50 and 75 mg per 100 g of the living weight evokes a 24 and 40% decrease, respectively, in the level of amino acylation of the rat livel tRNA by 14C-tryptophan. The ability of accepting 14C-tryptophan in total preparations of the experimental rats liver tRNA considerably lower as compared to norm. A short-term heating in the presence of magnesium ions partially restores their decreased acceptor ability. This gives ground to suppose that the molecules of tRNAtr in the total preparation of the rat liver tRNA with a great tryptophan excess in the organism partially change their conformation and this is one of the reasons of the decrease in the level of tRNA amino acylation by 14C-tryptophan. The decrease in the protein synthesis at the first stage with the presence of a great tryptophan excess in the organism is evident to be also connected with the inhibition of tryptophanyl-tRNA-synthetase activity.

Animals↗

PubMed2007

Nitrosation of N-terminally blocked tryptophan and tryptophan-containing peptides by peroxynitrite.

Tryptophan is known to be a major target of oxidative stress and to take part in electron transfer. In proteins, its fluorescence is extinguished after treatment with oxidative agents, like peroxynitrite (ONOO(-)/ONOOH) - the product of the reaction of NO* and superoxide anion (O*(2)(-)) radicals. The main reactions of N-blocked tryptophan derivatives (melatonin or N-acetyl-L-tryptophan) exposed to peroxynitrite at physiological pH are oxidation to formylkynuramine or formylkynurenine, respectively, and nitrosation, which leads to substituted 1-nitrosoindoles. Here we show that peroxynitrite-induced nitrosation is specific to N-blocked L-tryptophan derivatives and is not obtained with free L-tryptophan. Such a nitrosation can be evaluated by using 4,5-diaminofluorescein (DAF-2), which is converted to the fluorescent triazolofluorescein by NO* donors and nitrosating agents. N-acetyl-L-tryptophan was shown to be twice as efficient as melatonin in transferring NO from peroxynitrite to DAF-2. DAF-2 responses were then used to assess the ability of a series of L-tryptophan-containing peptides to give transient N-nitrosoindoles upon treatment with peroxynitrite. Many peptides proved not to be susceptible to nitrosation under these conditions. However, the N-terminally blocked peptide of endothelin-1 (Ac-Asp-Ile-Ile-Trp) reacted in a very similar fashion to melatonin; this shows that tryptophan residue nitrosation could occur when it was exposed to peroxynitrite.

Fluorescein↗

PubMed1981

Kinetics of L-tryptophan in depressive patients: a possible correlation between the plasma concentrations of L-tryptophan and some psychiatric rating scales.

The plasma concentration and flux of L-tryptophan are abnormal in primary depressive patients, according to the literature. The plasma concentrations of L-tryptophan over a 6-h period after ingestion of 5 g L-tryptophan were investigated and did not differ significantly between depressive patients and controls during the absorption, distribution, and elimination phases. There was no correlation between the plasma concentrations with anxiety or depression scores, or with the excretion in urine of 17-hydroxycorticosteroids and xanthurenic acid during the 24 h after L-tryptophan. Treatment with either 125 mg pyridoxine (three times daily with meals) and L-tryptophan (3 g at 10 PM) or with maprotiline (100 mg at 10 PM) had no influence on the plasma concentrations of L-tryptophan after 2 or 4 weeks of treatment. This excludes L-tryptophan deficiency as a pathogenic factor of depression in the patients studied. No kinetic differences could be demonstrated in the depressive patients, making differences in body compartments or flux of L-tryptophan unlikely to be of pathogenic importance to depression.

Chromatography, High Pressure Liquid↗

PubMed1995

The effects of an inhibitor of tryptophan 2,3-dioxygenase and a combined inhibitor of tryptophan 2,3-dioxygenase and 5-HT reuptake in the rat.

The effects of a novel inhibitor 680C91 ((E)-6-fluoro-3-[2-(3-pyridyl)vinyl]-1H-indole) of the key enzyme of tryptophan catabolism tryptophan 2,3-dioxygenase (TDO), and a novel inhibitor 709W92 ((E)-6-fluoro-3-[2-(4-pyridyl)vinyl]-1H-indole), of both TDO and 5-hydroxytryptamine (5-HT) reuptake, were examined on tryptophan catabolism, cerebrospinal fluid (CSF) concentrations of tryptophan and 5-HT and serotonergic-mediated physiology and behaviour in the rat. The catabolism of L-[ring-2-14C]tryptophan in vivo was completely inhibited by prior administration of 709W92. 709W92, but not 680C91, potentiated head-twitch produced by 5-hydroxytryptophan, prevented head-twitch and whole brain 5-HT depletion produced by p-chloroamphetamine and rapidly decreased dorsal raphe firing. Both 709W92 and 680C91 elevated CSF tryptophan by up to 260% of basal concentration. A maximally effective dose of 680C91 elevated a global measure of brain extracellular 5-HT (CSF 5-HT) to concentrations similar to those seen maximally after exogenous tryptophan administration (approx 170% of basal). Maximally effective doses of 709W92 increased CSF 5-HT to concentrations comparable to those seen after tryptophan and 5-HT reuptake inhibitor coadministration (approx 900% of basal) and to concentrations greater than those achieved maximally with serotonergically active antidepressant monotherapy (approx 500% of basal). 709W92 did not elevate CSF 5-HT to concentrations associated with the serotonin syndrome (approx 3000% of basal). The combined TDO inhibitor/5-HT reuptake inhibitor, 709W92, showed anxiolytic activity in the rat-pup vocalization model of anxiety. These results show that 709W92 (a novel inhibitor of both TDO and 5-HT reuptake), can produce an elevation of CSF 5-HT similar to that achieved with a serotonin reuptake inhibitor/tryptophan combination therapy but with a more sustained timecourse; such compounds may therefore have superior antidepressant efficacy in the clinic.

Animals↗

PubMed2005

Modification of tryptophan and tryptophan residues in proteins by reactive nitrogen species.

Formation of 3-nitrotyrosine by the reaction between reactive nitrogen species (RNS) and tyrosine residues in proteins has been analyzed extensively and it is used widely as a biomarker of pathophysiological and physiological conditions mediated by RNS. In contrast, few studies on the nitration of tryptophan have been reported. This review provides an overview of the studies on tryptophan modifications by RNS and points out the possible importance of its modification in pathophysiological and physiological conditions. Free tryptophan can be modified to several nitrated products (1-, 4-, 5-, 6-, and 7-), 1-N-nitroso product, and several oxidized products by reaction with various RNS, depending on the conditions used. Among them, 1-N-nitrosotryptophan and 6-nitrotryptophan (6-NO(2)Trp) have been found as the abundant products in the reaction with peroxynitrite, and 6-NO(2)Trp has been the most abundant product in the reaction with the peroxidase/hydrogen peroxide/nitrite systems. 6-NO(2)Trp has also been observed as the most abundant nitrated product of the reactions between peroxynitrite or myeloperoxidase/hydrogen peroxide/nitrite and tryptophan residues both in human Cu,Zn-superoxide dismutase and in bovine serum albumin, as well as the reaction of peroxynitrite with myoglobin and hemoglobin. Several oxidized products have also been identified in the modified Cu,Zn-SOD. However, no 1-N-nitrosotryptophan and 1-N-nitrotryptophan has been observed in the proteins reacted with peroxynitrite or the myeloperoxidase/H(2)O(2)/nitrite system. The modification of tryptophan residues in proteins may occur at a more limited number of sites in vivo than that of tyrosine residues, since tryptophan residues are more buried inside proteins and exist less frequently in proteins, generally. However, surface-exposed tryptophan residues tend to participate in the interaction with the other molecules, therefore the modification of those tryptophans may result in modulation of the specific interaction of proteins and enzymes with other molecules.

Animals↗

PubMed1997

Ionization, partitioning, and dynamics of tryptophan octyl ester: implications for membrane-bound tryptophan residues.

The presence of tryptophan residues as intrinsic fluorophores in most proteins makes them an obvious choice for fluorescence spectroscopic analyses of such proteins. Membrane proteins have been reported to have a significantly higher tryptophan content than soluble proteins. The role of tryptophan residues in the structure and function of membrane proteins has attracted a lot of attention. Tryptophan residues in membrane proteins and peptides are believed to be distributed asymmetrically toward the interfacial region. Tryptophan octyl ester (TOE) is an important model for membrane-bound tryptophan residues. We have characterized this molecule as a fluorescent membrane probe in terms of its ionization, partitioning, and motional characteristics in unilamellar vesicles of dioleoylphosphatidylcholine. The ionization property of this molecule in model membranes has been studied by utilizing its pH-dependent fluorescence characteristics. Analysis of pH-dependent fluorescence intensity and emission maximum shows that deprotonation of the alpha-amino group of TOE occurs with an apparent pKa of approximately 7.5 in the membrane. The fluorescence lifetime of membrane-bound TOE also shows pH dependence. The fluorescence lifetimes of TOE have been interpreted by using the rotamer model for the fluorescence decay of tryptophan. Membrane/water partition coefficients of TOE were measured in both its protonated and deprotonated forms. No appreciable difference was found in its partitioning behavior with ionization. Analysis of fluorescence polarization of TOE as a function of pH showed that there is a decrease in polarization with increasing pH, implying more rotational freedom on deprotonation. This is further supported by pH-dependent red edge excitation shift and the apparent rotational correlation time of membrane-bound TOE. TOE should prove useful in monitoring the organization and dynamics of tryptophan residues incorporated into membranes.

Fluorescent Dyes↗

PubMed1997

A tryptophan-2-monooxygenase based amperometric biosensor for L-tryptophan determination: use of a competitive inhibitor as a tool for selectivity increase.

A new flow-injection amperometric biosensor based on immobilized tryptophan-2-monooxygenase (TMO) has been developed for reagentless L-tryptophan determination. Concentrations of L-tryptophan between 0.1 and 50 mM could be measured with the linear part of the calibration curve between 0.1 and 2 mM. The response time was 30 s and the total analysis time was less than 3 min. The biosensor retained activity for greater than 4 months, when operated daily at 25 degrees C and stored at 8 degrees C. The biosensor was characterized by a relatively high sensitivity to phenylalanine (54% that of L-tryptophan), a modest response to L-methionine (less than 6%) and virtually no response to other amino acids. However, the biosensor selectivity to L-tryptophan could be dramatically increased when indoleacetamide (IA), a competitive inhibitor of TMO, was introduced. In the presence of 10 microM IA, the biosensor response to L-phenylalanine decreased to 7-4% of the unaffected rate for L-tryptophan. In the absence of L-tryptophan and IA the biosensor could be used for L-phenylalanine determination in the concentration range from 1 to 50 mM. The biosensor was successfully used for L-tryptophan determination in nutritional broth.

Biosensing Techniques↗

PubMed2001

The mechanism of tryptophan induction of tryptophanase operon expression: tryptophan inhibits release factor-mediated cleavage of TnaC-peptidyl-tRNA(Pro).

Expression of the tryptophanase (tna) operon of Escherichia coli is regulated by catabolite repression and tryptophan-induced transcription antitermination. In a previous study, we reproduced the regulatory features of this operon observed in vivo by using an in vitro S-30 system. We also found that, under inducing conditions, the leader peptidyl-tRNA (TnaC-peptidyl-tRNA(Pro)) is not cleaved; it accumulates in the S-30 reaction mixture. In this paper, we examine the requirements for TnaC-peptidyl-tRNA(Pro) accumulation and cleavage, in vitro. We show that this peptidyl-tRNA remains bound to the translating ribosome. Removal of free tryptophan and addition of release factor 1 or 2 leads to hydrolysis of TnaC-peptidyl-tRNA(Pro) and release of TnaC from the ribosome-mRNA complex. Release factor-mediated cleavage is prevented by the addition of tryptophan. TnaC of the ribosome-bound TnaC-peptidyl-tRNA(Pro) was transferable to puromycin. This transfer was also blocked by tryptophan. Tests with various tryptophan analogs as substitutes for tryptophan revealed the existence of strict structural requirements for tryptophan action. Our findings demonstrate that the addition of tryptophan to ribosomes bearing nascent TnaC-peptidyl-tRNA(Pro) inhibits both TnaC peptidyl-tRNA(Pro) hydrolysis and TnaC peptidyl transfer. The associated translating ribosome therefore remains attached to the leader transcript where it blocks Rho factor binding and subsequent transcription termination.

Bacterial Proteins↗

PubMed1992

Tryptophan fortification of adapted formula increases plasma tryptophan concentrations to levels not different from those found in breast-fed infants.

Several recent studies have demonstrated significantly lower plasma total tryptophan concentrations in formula-fed than in breast-fed infants. We have measured preprandial plasma amino acid concentrations in infants breast-fed or fed a formula with a protein concentration of 1.57 g/dl and with a whey/casein ratio of 60:40 or a formula with a protein concentration of 1.37 g/dl and a whey/casein ratio of 40:60 and fortified with 10 mg/dl (15 mg/100 kcal) of tryptophan. Healthy term infants (10 per group) were either breast-fed from birth or randomly assigned to one of the two study formulas. At 4 and 12 weeks of age, anthropometric measurements were performed and blood samples were obtained. During the study period of 12 weeks, all infants showed normal growth (weight, length, and head circumference) and there were no statistically significant differences between the groups. The plasma concentrations of the essential amino acids phenylalanine, threonine, valine, and lysine were significantly lower in the breast-fed group than in both formula-fed groups. For tyrosine, methionine, leucine, histidine, isoleucine, and arginine, no significant differences could be found between the feeding groups. Concentration of total plasma tryptophan was significantly higher in the breast-fed group than in the group fed the tryptophan-unfortified formula, but no statistically significant difference could be found between the plasma tryptophan concentration in the breast-fed group versus the group fed the tryptophan-fortified formula. The results indicate that tryptophan fortification of adapted formula is necessary to achieve plasma total tryptophan concentrations similar to those found in breast-fed infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Essential↗

PubMed1976

Parallel variation of ventricular CSF tryptophan and free serum tryptophan in man.

Tryptophan was measured in the ventricular CSE and serum and the neutral amino acids leucine, isoleucine, valine, phenylalanine, and tyrosine were measured in the serum of two cases with ventricular drains. Samples were taken every two hours for 24 hours in one case and for 16 hours in the other. The CSF tryptophan was correlated significantly with the free--that is, non-albumin-bound--serum tryptophan but not with the total serum tryptophan. CSF tryptophan was not correlated significantly with the ratio of free serum tryptophan to the sum of the neutral amino acids. These data suggest that, in man, brain tryptophan concentrations are influenced by the free and not the total serum tryptophan and that physiological variations of the neutral amino acids do not appreciably influence the concentration of brain trytophan.

Adult↗

PubMed1981

Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human lumbar and cisternal cerebrospinal fluid.

Tryptophan 5-hydroxyindoleacetic acid and indoleacetic acid were measured in cerebrospinal fluid taken during pneumoencephalography from patients, some of whom took a 3 g or 6 g tryptophan load at various times before. Measurements were made on both lumbar and cisternal cerebrospinal fluid and the results showed similarities between indoleamine metabolism in human brain and spinal cord. Our data suggested that (1) the blood-brain barrier active transport system for tryptophan is not far from saturation with tryptophan and the rate-limiting enzyme in 5-hydroxytryptamine (5HT) synthesis, tryptophan hydroxylase, is about half saturated. Therefore, both 3 g and 6 g tryptophan loads produced the same maximum rise in 5HT synthesis of just under 100%, (2) tryptamine differs from 5HT in two respects. It is more sensitive to changes in tryptophan availability than 5HT and the 6 g load increased brain tryptamine metabolism more than the 3 g load; also some of the tryptamine in brain is derived from peripheral sources and diffuses from blood to brain, (3) although the brain tryptamine content is much lower than that of 5HT, its rate of metabolism as indicated by CSF metabolite levels is not. In controls the rate of tryptamine metabolism is 15% of the rate of 5HT metabolism and this can increase to 40% after a 6 g tryptophan load.

Adolescent↗

PubMed2004

Synthesis and in vitro cytotoxicity studies of novel L-tryptophan-polyamide conjugates and L-tryptophan dimers linked with aliphatic chains and polyamides.

The synthesis and biological evaluation of novel L-tryptophan pyrrole, imidazole polyamide conjugates (16-21), L-tryptophan-glycosylated pyrrole polyamide conjugates (28-30), L-tryptophan dimers (37-42) with straight carbon links of varying length, and L-tryptophan dimers (68-73) linked with pyrrole and imidazole polyamide from both sides by a flexible methylene chain of variable length are described. The compounds were prepared with varying numbers of pyrrole- and/or imidazole-containing polyamides and glycosylated pyrrole polyamides to determine the structural requirements for optimal in vitro antitumor activity. The compounds listed in Table 1 have been evaluated in a three cell line, one dose primary anticancer assay. The compounds listed in Table 2 have been evaluated against nine panels of 60 human cancer cell lines including leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer. It is observed from the initial cytotoxic data (Table 1) that compounds 16-19, 28-30, 68-69, and 71-73 have varying cytotoxic potencies against the three cancer cell lines. It is also observed, from the biological data from Table 2 for compounds 20-21, 37-42, and 70 against the 60 different tumor cells, that the L-tryptophan dimers 37-42 linked by a different number of carbon chains are more active than the L-tryptophan dimers linked by pyrrole or imidazole polyamides. The cytotoxic potency in tryptophan dimers, linked by a different number of carbon atoms increased the number of carbons between the two L-tryptophan rings.

Antineoplastic Agents↗

PubMed2006

The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells.

Tryptophan catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan catabolism affects T cell responses remain unclear. We provide evidence that the short-term, combined effects of tryptophan deprivation and tryptophan catabolites result in GCN2 kinase-dependent down-regulation of the TCR zeta-chain in murine CD8+ T cells. TCR zeta down-regulation can be demonstrated in vivo and is associated with an impaired cytotoxic effector function in vitro. The longer-term effects of tryptophan catabolism include the emergence of a regulatory phenotype in naive CD4+CD25- T cells via TGF-beta induction of the forkhead transcription factor Foxp3. Such converted cells appear to be CD25+, CD69-, CD45RBlow, CD62L+, CTLA-4+, BTLAlow and GITR+, and are capable of effective control of diabetogenic T cells when transferred in vivo. Thus, both tryptophan starvation and tryptophan catabolites contribute to establishing a regulatory environment affecting CD8+ as well as CD4+ T cell function, and not only is tryptophan catabolism an effector mechanism of tolerance, but it also results in GCN2-dependent generation of autoimmune-preventive regulatory T cells.

Animals↗

PubMed1991

L-tryptophan-induced eosinophilia-myalgia syndrome. II. Partial correction of abnormal tryptophan metabolism by pyridoxine.

Abnormal metabolism of tryptophan is one of the possible aetiological factors in the L-tryptophan-induced eosinophilia-myalgia syndrome (EMS). We studied the plasma levels of tryptophan and serotonin and the urinary excretion of kynurenine and 5-hydroxyindoleacetic acid after oral intake of L-tryptophan in 1 subject with EMS and 2 healthy subjects. The test was repeated with concomitant administration of pyridoxine. In the patient there were elevated levels of plasma tryptophan during the loading and increased elimination of kynurenine in the urine both during and after the L-tryptophan test. During pyridoxine administration tryptophan levels and kynurenine elimination were much reduced, and kynurenine elimination was similar to that of controls. This study (i) confirms that an abnormal metabolism of L-tryptophan occurs in EMS patients and (ii) shows that this can be corrected by pyridoxine.

Adult↗

PubMed1962

Tryptophanase-tryptophan synthetase systems in Escherichia coli. I. Effect of tryptophan and related compounds.

Freundlich, Martin (University of Minnesota, Minneapolis) and Herman C. Lichstein. Tryptophanase-tryptophan synthetase systems in Escherichia coli. I. Effect of tryptophan and related compounds. J. Bacteriol. 84:979-987. 1962.-The effect of tryptophan and related compounds on tryptophanase and tryptophan synthetase formation in Escherichia coli was determined. Several of these compounds stimulated the formation of tryptophanase while concomitantly decreasing the production of synthetase. A number of tryptophan analogues were found to inhibit growth. The possible mode of action of these substances was examined further. 5-Hydroxytryptophan greatly inhibited the formation of synthetase and also reduced growth. Its inhibitory action on growth was attributed, at least partially, to the false feedback inhibition of anthranilic acid formation. Tryptamine was found to be a potent inhibitor of the activity of synthetase, as well as of the enzyme(s) involved in the synthesis of anthranilic acid from shikimic acid. However, growth reduction was only partially reversed by tryptophan. Indole-3-acetic acid and indole-3-propionic acid decreased growth and increased the formation of synthetase six- to eightfold. The action of these compounds was ascribed to their ability to block the endogenous formation of tryptophan.

Escherichia coli↗

PubMed1993

Enantiospecific syntheses of alpha-(fluoromethyl)tryptophan analogues: interactions with tryptophan hydroxylase and aromatic L-amino acid decarboxylase.

alpha-Fluoromethyl amino acids are enzyme-activated irreversible inhibitors of amino acid decarboxylases. Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible for the final step in the biosynthesis of both dopamine and serotonin via decarboxylation of L-dopa and 5-hydroxy-L-tryptophan, respectively. Our goal is to utilize antagonists of the serotonin-producing enzymes (tryptophan hydroxylase and AADC) as the basis for a chemotherapeutic approach to the treatment of carcinoid tumors, a rare tumor type characterized by the overproduction of serotonin. We report here an enantiospecific synthesis of alpha(S)-(fluoromethyl)tryptophan [(S)-11a] and alpha(S)-(fluoromethyl)-5-hydroxytryptophan [(S)-11b], as well as the (R)-enantiomers, based upon recent methodology involving the face-selective alkylation of cyclic tryptophan tautomers. Our synthetic route provided both enantiomers of 11a and 11b with greater than 97% enantiomeric purity based upon evaluation of the NMR spectra of their Mosher's acid derivatives. (S)-11a was evaluated as a substrate for P815 tryptophan hydroxylase and determined to have an apparent Km of 4.31 +/- 1.07 mM, essentially half the value previously reported for the racemic mixture of 11a with rat brain stem tryptophan hydroxylase. (R)-11a was not a substrate for P815 tryptophan hydroxylase. (S)-11b was evaluated as an enzyme-activated irreversible inhibitor of murine liver AADC and determined to have a KI of 24.3 +/- 3.01 microM and a k2 of 2.26 +/- 0.44 min-1. (R)-11b was not an inhibitor of murine liver AADC.

5-Hydroxytryptophan↗