Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT03141 (L-tyrosine)
 2,375 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When a hexapeptide, Leu-Trp-Met-Arg-Phe-Ala, or a pentoapeptide, Leu-Trp-Met-Arg-Phe, was incubated in vitro with a purified aminooligopeptidase from rat small intestinal mucosa, the respective C-terminal dipeptides, Phe-Ala and Arg-Phe, were observed to be resistant to hydrolysis. The resistance of these C-terminal dipeptides to hydrolysis was found to be due mainly to the accumulation of inhibitory hydrophobic amino acids liberated in the incubation mixture. The hydrolysis of various peptides by the brush-border membrane peptidase is inhibited to a varying extent by the hydrophobic amino acids L-tryptophan, L-methionine, L-isoleucine, L-leucine, L-tyrosine, and L-phenylalanine, but not the D-form of these amino acids. The inhibition of the hydrolysis of three dipeptides by hydrophobic amino acids showed these amino acids to be competitive inhibitors (same Vmax, the maximal velocity of the enzyme reaction; different Km, the substrate concentration at which the enzyme reaction is half maximal) of one of the dipeptides while exhibiting a mode of inhibition that was not competitive (different Vmax, different Km) with either of the other two dipeptides. These data indicate that the effect of amino acids on the hydrolytic rate of the brush-border membrane aminooligopeptidases must be considered in studies of intestinal hydrolysis and absorption of peptides.
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PMID:Effect of amino acids on purified rat intestinal brush-border membrane aminooligopeptidase. 75 53

Two enzymes, tryptophan transaminase and indolepyruvate C-methyltransferase, which are active in the initial steps of the biosynthetic pathway of the antibiotic indolmycin, have been detected and partially purified from cell-free extracts of Streptomyces griseus. The transaminase has been purified 3-fold by ammonium sulfate fractionation. At this stage of purification, it catalyzes the alpha-ketoglutarate and pyridoxal phosphate-dependent transamination of L-tryptophan, 3-methyltryptophan, L-pphenylalanine, and L-tyrosine. The C-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to position 3 of the aliphatic side chain of indolepyruvate. No cofactors are required. The C-methyltransferase has been purified 110-fold by ammonium sulfate fractionation, Sephadex G-150 gel filtration, DEAE-Sephadex column chromotography, and Bio-Gel A-5m gel filtration. The enzyme has a broad pH optimum of 7.5 to 8.5. A molecular weight of 55,000 +/- 5,000 has been determined by Sephadex G-200 gel filtration with reference proteins and a molecular weight of 58,000 +/- 8,000 has been determined by sucrose density gradient centrifugation. The enzyme is relatively stable at temperatures of 0-5 degrees but is destroyed by freezing or by heating. The C-methyltransferase is inhibited strongly by the thiol reagents p-chloromercuribenzoate and N-ethylmaleimide. The Zn2+ and Fe2+ chelators 1,10-phenanthroline and 2,2'-bipyridine also inhibit the enzyme activity but EDTA does not. Michaelis-Menten constants have been determined for the 110-fold purified enzyme as 1.2 X 10(-5) M for S-adenosylmethionine and 4.8 X 10(-6) M for indolepyruvate. The enzyme activity in the crude extract is inhibited competitively by indolmycin (Ki equals 2.3 mM) and L-tryptophan (Ki equals 0.17 mM), but these effects are not observed after the enzyme has been passed through the Sephades G-150 column during purification. The crude extract is capable of methylating phenylpyruvate and p-hydroxyphenylpyruvate but this capability is lost upon purification of the indolepyruvate C-methyltransferase activity. No methylation of L-tryptophan occurs under the conditions used.
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PMID:Isolation and characterization of tryptophan transaminase and indolepyruvate C-methyltransferase. Enzymes involved in indolmycin biosynthesis in Streptomyces griseus. 80 39

Human fibroblast interferon binds to L-tryptophan, D-tryptophan, L-phenylalanine, and L-tyrosine, all immobilized directly to cyanogen bromide-activated agarose, as well as to L-tryptophan and D-tryptophan methyl ester, both immobilized via molecular arms. The retention of fibroblast interferon is selective and results in a 2300-fold purification. Human leukocyte interferon binds neither to L-tryptophan attached directly to an agarose matrix nor to L-tryptophan immobilized via a molecular arm; it binds, however, to immobilized L-tryptophyl-L-tryptophan and L-tryptophyl-L-tryrosine. When retained, both interferons cannot be displaced unless ethylene glycol is included in the eluant, indicating a hydrophobic interaction. The interaction takes place under physiologic solvent conditions, thus revealing the high intrinsic hydrophobicity of both interferons.
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PMID:Interaction of human interferons with immobilized hydrophobic amino acids and dipeptides. 95 90

11-Demethyltomaymycin, an antitumor antibiotic produced by Streptomyces achromogenes, and its biologically inactive metabolite oxotomaymycin are biosynthesized from L-tyrosine, DL-tryptophan, and L-methionine. The anthranilate part of 11-demethyltomaymycin is derived from tryptophan probably via the kynurenine pathway. The predominant loss of tritium from DL-[5-3H]tryptophan, during its conversion to 11-demethyltomaymycin and oxotomaymycin is interpreted to mean by NIH shift rules, that the main pathway to the 5-methoxy-4-hydroxy anthranilate moiety is through hydroxylation at C-8 prior to hydroxylation at C-7. The methoxy carbon is derived from the S-methyl group of methionine by transfer of an intact methyl group. The ethylideneproline moiety of 11-demethyltomaymycin is biosynthesized from tyrosine, without a 1-carbon unit from methionine. The results of biosynthetic feeding experiments with L-[1-14C, 3- or 5-3H]tyrosine are consistent with a "meta" or extradiol cleavage of 6,7-dihydroxycyclodopa as has also been demonstrated previously for anthramycin and lincomycin A. An experiment in which L-[1-14C, Ala-2,3-3H]tyrosine was fed showed that both the beta hydrogens of this amino acids are retained in 11-demethyltomaymycin. It has been demonstrated in cultures and washed cell preparations that 11-demethyltomaymycin is enzymatically converted to oxotomaymycin by an intracellular constitutive enzyme. Conversion of oxotomaymycin to 11-demethyltomaymycin by these same preparations could not be demonstrated. The enzymatic activity associated with the conversion of 11-demethyltomaymycin to oxotomaymycin is not limited to the 11-demethyltomaymycin to oxotomaymycin is not limited to the 11-demethyltomaymycin production phase, since trophophase cells and even cells from 11-demethyltomaymycin nonproducing cultures of S. achromogenes were equally active in converting 11-demethyltomaymycin to oxotomaymycin.
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PMID:Pyrrolo[1,4]benzodiazepine antibiotics. Biosynthesis of the antitumor antibiotic 11-demethyltomaymycin and its biologically inactive metabolite oxotomaymycin by Streptomyces achromogenes. 108 63

A chemically defined medium for Veillonella parvula and V. alcalescens is described. Some nutritional aspects of the two strains used were examined: the optimum concentration of reducing agents, the requirements for amino acids, diamines, vitamins and other growth factors, and the conditions needed for well balanced nutrition. No specific requirements for single amino acids were observed. A combination of L-cysteine, DL-aspartic acid, L-glutamic acid, L-serine and L-tyrosine, promoted growth. In V. alcalescens, serine could substitute both arginine and tryptophan (or histidine). No growth was obtained with ammonium salts as the sole N source. Decarboxylation of L-ornithine, L-lysine and L-arginine was not demonstrated in the Veillonella parvula strain, which required putrescine or cadaverine for growth. Spermine, spermidine, L-lysine, L-ornithine and L-arginine, could not substitute putrescine in Veillonella parvula. Veillonella alcalescens, which does not require putrescine in the medium, was able to decarboxylate L-ornithine while forming putrescine.
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PMID:Chemically defined media for growing anaerobic bacteria of the genus Veillonella. 108 58

By treating porcine and bovine pepsins with H2O2 at pH 3.2, 3.5 of the 4 methionine residues of porcine pepsin and 1.6 of the 3 residues of bovine pepsin were oxidized to methionine sulfoxide. The effect of modification on activity varied with the substrate. There were no significant changes in catalytic constants in the hydrolysis of acetyl-L-phenylalanyl-L-tyrosine by both pepsins and in the hydrolysis of benzyloxycarbonyl-L-glutamyl-L-tyrosine by porcine pepsin. Hydrolysis of benzyloxycarbonyl-L-glutamyl-L-tyrosine by bovine pepsin was too slow to measure. With benzyloxycarbonyl-L-histidyl-L-phenylalanyl-L-tryptophan ethyl ester as substrate, the modification decreased the catalytic efficiency (kcat/Km) by two-thirds for porcine pepsin and by half for bovine pepsin. With hemoglobin substrate, digestion was significantly less than with native pepsin for modified porcine pepsin, and slightly less for modified bovine pepsin. The results are interpreted as indicating the presence of a methionine residue that participates in the binding of long substrates, but is not close enough to the active site to reach short substrates. Cleavage of the modified pepsins with cyanogen bromide identified the methionine nearest the carboxyl terminus of both pepsins as a resiude that remained partially unmodified.
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PMID:Oxidation of methionine residues of porcine and bovine pepsins. 108 31

The efficiency of energy transfer between a fluorescent donor, L-tyrosine, and a fluorescent acceptor, L-tryptophan, has been determined in R'-L-Trp-L-Ala-L-Tyr-R", R-L-Trp-L-Ala-L-Ala-L-Tyr-R", and R'-L-Trp-Gly-L-Ala-L-Tyr-R" in ethanol solution. The protecting groups R' and R" were respectively tert-butyloxycarbonyl and methyl ester. A conformational theoretical analysis of molecules studied has been performed in parallel on the basis of semiempirical conformational potential energy function. In the theoretical models all the side chains have been represented by a methyl group. From the distribution of distances between chromophores obtained theoretically, transfer efficiencies have been computed assuming a random orientation of the chromophores (k-2 equals 2/3). The comparison of calculated efficiencies with the values determined experimentally for the same value of k-2 has been used as a check for the theoretical model. Both experimental and theoretical studies have been shown that the glycyl residue procudes a reduction of dimensions when it replaces in a tetrapeptide a residue with a beta-carbon atom such as the L-alanyl residue. However, only a qualitative agreement between experimental and theoretical values of the efficiencies has been obtained.
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PMID:Studies of the dimensions of oligopeptides by singlet-singlet energy, transfer and theoretical calculations. I. Influence of glycine on the dimensions of tetrapeptides. 112 85

1. Slices of rat cerebral cortex incubated aerobically at 37 degrees C in Krebs-Ringer-bicarbonate solution accumulated 3,4-L-dihydroxyphenylalanine (L-DOPA) against its concentration gradient. With 1 mM L-DOPA in the medium, tissue-water/medium concentration ratios of about 6 : 1 are reached, which are modified by the presence of other amino acids in the medium. 2. Kinetic analysis suggested that L-DOPA influx into brain cells occurred by at least two saturable processes, which show apparent Km values in the range of 10(-3) M and 10(-5) M, respectively. 3. Prior incubation of the slices in Na+-free (choline-containing) medium at 37 degrees C depressed their subsequent uptake of L-DOPA in normal Na+-containing medium; this inhibition did not appear when the preincubation was carried out at 0-4 degrees C. Besides this effect of preincubation, most of L-DOPA influx into brain slices was independent of the actual concentration of Na+ in the medium; the two saturable processes described in this article behaved similarly in this respect. 4. Most of L-DOPA uptake by the high-Km process is mediated by an agency that resembles the Na+-independent L system described in Ehrlich cells (Oxender, D. L. and Christensen, H. N. (1963) J. Biol. Chem. 238, 2686-2699), both in its specificity and in its participation in exchange phenomena. A lesser component of uptake by a type A mediation is also suggested as contributing to the high-Km process . 5. The kinetic and specificity properties of the low-Km process of L-DOPA uptake suggest a similarity between its mediation and that of the high-affinity systems for L-tyrosine and L-tryptophan found in brain tissue preparations (Belin, M. F. and Pujol, J. F. (1973) Experientia 29, 411-413; Bauman, A., Bourgoin, S., Benda, P., Glowinski, J. and Hamon, M. (1971 Brain Res. 66, 253-263).
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PMID:Characterization of transport systems for the transfer of 3,4-L-dihydroxyphenylalanine into slices of rat cerebral cortex. 118 75

1. Kynurenine-2-oxoglutarate aminotransferase (isoenzyme 1) was purified to homogeneity from the liver, brain and small intestine of rats by the same procedure. The three enzyme preparations had nearly identical pH optima, substrate specificities and molecular weights. Isoenzyme 1 was active with 2-oxoglutarate but not with pyruvate as amino acceptor, and utilized a wide range of amino acids as amino donors. Amino acids were effective in the following order to activity: L-aspartate greater than L-tyrosine greater than L-phenylalanine greater than L-tryptophan greater than 5-hydroxy-L-tryptophan greater than L-kynurenine. The molecular weight was approximately 88 000 as determined by sucrose-density-gradient centrifugation. The pH optimum was between 8.0 and 8.5. On the basis of substrate specificity, substrate inhibition, subcellular distribution and polyacrylamide-disc-gel electrophoresis, it is suggested that liver, brain and small intestinal kynurenine-2-oxoglutarate aminotransferase (isoenzyme 1) is identical with mitochondrial tyrosine-2-oxoglutarate aminotransferase and also with mitochondrial aspartate-2-oxoglutarate aminotransferase. 2. An additional kynurenine-2-oxoglutarate aminotransferase (isoenzyme 2) was purified from the liver. This enzyme was specific for 2-oxoglutarate and L-kynurenine. Sucrose-density-gradient centrifugation gave a molecular weight of approximately 100 000. The pH optimum was between 6.0 and 6.5. This enzyme was not detected in the brain or small intestine.
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PMID:Purification and characterization of kynurenine--2-oxoglutarate aminotransferase from the liver, brain and small intestine of rats. 121 85

D,L-tryptophan[benzene ring-14C (U)] and D,L-tryptophan (methylene-14C) are incorporated significantly into melanin of Harding-Passey mouse melanoma. D,L-5-hydroxytryptophan (methylene-14C) and 5-hydroxytryptamine-3-14C (serotonin) gave an incorporation of radioactivity into melanin significantly lower than tryptophan. D,L-tyrosine-2-14C was incorporated into melanin as well as tryptophan. Therefore tryptophan must be considered an important precursor in the biogenesis of melanins too.
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PMID:Studies on melanogenesis of tryptophan in Harding-Passey mouse melanoma. 124 96


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