Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.3.4.6 (urease)
7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydroxamic acids have been reported to be potent and specific inhibitors of urease (EC 3.5.1.5) activity of plant and bacterial origin. The present investigation was performed on the inhibitory effect of hydroxamic acid derivatives of naturally occurring amino acids on the urease activity of the Jack Bean and the alimentary tracts of rats. Methionine-hydroxamic acid was the most powerful inhibitor (I50=3.9 X 10(-6) M) among nineteen alpha-aminoacyl hydroxamic acids. Phenylalanine-, serine-, alanine-, glycine-, histidine-, threonine-, leucine-, and arginine-hydroxamic acids followed, in order of decreasing inhibitory power. The inhibition proceeded with time at a comparable rate to fatty acyl hydroxamic acid inhibition. The I50 values of alpha-aminoacyl hydroxamic acids were found to be almost equal to those of the corresponding fatty acyl hydroxamic acids. This fact shows that the alpha-amino group did not affect inhibitory power. However, aspartic-beta-, lysine-, and glutamic-gamma-hydroxamic acids, in descending order, were much less inhibitory, probably due to the presence of a carboxyl or omega-amino group. Furthermore, the pH optimum of the inhibition shifted to lower pH in the presence of a carboxyl group, and to a higher pH in e presence of an amino group. The results suggest that the dissociation of an acidic or a basic group reduces the inhibitory power of hydroxamic acid. Hydroxamic acid inhibits urease activity with strict specificity, excpet for aspartic-beta-hydroxamic acid, which inhibited asparaginase competitively. Hydroxamic acid derivatives of amino acids inhibited not only the urease activity of the Jack Bean, but also that of the caecum and ileum parts of the rat intestine.
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PMID:Inhibition of urease activity by hydroxamic acid derivatives of amino acids. 23 68

Nitrogen-free analogues of essential amino acids, when administered with those essential amino acids for which analogues are ineffective or unavailable, exert three actions that may be beneficial in protein-deficient or protein-intolerant subjects. First, they bring about an increase in the concentrations of essential amino acids in the blood at the expense of the concentrations of certain non-essential amino acids, notably alanine and glutamine. This effect is most readily demonstrated in children with congenital defects of the urea cycle enzymes, but can also be seen during daily therapy of adults with portal-systemic encephalopathy. Second, these compounds promote nitrogen balance through their suppressive effect on urea synthesis (an effect not attributable to re-utilization of ammonia derived from urease action in the gut). This action is demonstrable in obese subjects who are already conserving nitrogen maximally at the end of a prolonged fast and can also be shown in the first week of fasting when the branched-chain keto acids alone are administered. In both situations, improved nitrogen conservation persists long after the analogues are metabolized, suggesting enzyme adaptations. In chronic uremics, nitrogen balance can be maintained in some (but not all) patients on very low nitrogen intakes. Third, these mixtures may delay or reverse the progressive decline in glomerular filtration rate characteristic of chronic renal failure in some cases: thus, for example, 5 of 6 patients taken off chronic dialysis have maintained lower serum urea concentrations without evidence of protein malnutrition for periods of 2-24 months.
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PMID:Evidence for an anabolic action of essential amino acid analogues in uremia and starvation. 107 39

Gyrocotyle fimbriata isolated from the spiral valve of Hydrolagus colliei were washed, then held in a filtered seawater-penicillin-Tris buffer medium. Ammonia and urea release to the medium declined together and ammonia production was minimal when the urea concentration was below detectable limits. Alanine and smaller amounts of glycine were released to the medium at a more constant rate. After 12 hr the alanine-glycine excretion was more than 20 times the ammonia excretion. L-arginine, L-serine, L-histidine, and urea were most effective in stimulating ammonia production by whole worms; other L-amino acids were essentially ineffective. L-glutamate dehydrogenase, L-amino acid oxidase, uricase, and ornithine transcarbamylase were below detectable levels. L-serine dehydrase, L-arginase, L-histidase, and urease were detected in tissue homogenates and probably account for most of the endogenous ammonia production. L-arginase has a molecular weight of 28,000 by Sehpadex gel filtration. The high levels of glutamate-pyruvate transaminase and lower levels of glutamate-oxalacetate transaminase correlate with the high level of alanine excretion. It is concluded that (1) ammonia production is not strongly linked to the overall energy metabolism of Gyrocotyle and is probably a result of a series of unrelated enzymatic reactions such as the action of urease of urea from the tissue of the rat fish, and (2) alanine and glycine are the major nitrogen excretory products and their production is linked to the energy metabolism of Gyrocotyle.
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PMID:Ammonia formation and amino acid excretion by Gyrocotyle fimbriata (Cestoidea). 111 78

1. Isolated hepatocytes were used to establish the reasons for the accumulation of aspartate, previously observed when the isolated rat liver was perfused with ethanol in the presence of alanine or ammonium lactate. 2. The isolated cells did not form aspartate when incubated with alanine and ethanol, but much aspartate was formed on incubation with ammonium lactate and ethanol. 3. Urea was the main nitrogenous product on incubation with alanine, in contrast with the perfused liver, where major quantities of NH4+ are also formed. When the formation of urea was nullified by the addition of urease, alanine plus ethanol caused aspartate formation, indicating that aspartate formation depends on the presence of critical concentrations of NH4+. 4. The accumulated aspartate was present in the cytosol. Ethanol halved the content of 2-oxoglutarate in the cytosol and more than trebled that of glutamate in the mitochondria. 5. The findings support the assumption that 2-oxoglutarate formed by the mitochondrial aspartate aminotransferase is not translocated to the cytosol in the presence of ethanol and NH4+, because it is rapidly converted into glutamate, the dehydrogenation of ethanol providing the required NADH. Aspartate, however, is translocated to the cytosol and accumulates there because of the lack of stoicheiometric amounts of oxoglutarate.
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PMID:The accumulation of aspartate in the presence of ethanol in rat liver. 120 Oct 7

Cysteine 319 in the large subunit of Klebsiella aerogenes urease was identified as an essential catalytic residue based on chemical modification studies (Todd, M.J., and Hausinger, R.P. (1991) J. Biol. Chem. 266, 24327-24331). Through site-directed mutagenesis, this cysteine has been changed independently to alanine, serine, aspartate, and tyrosine. None of these mutations (C319A, C319S, C319D, and C319Y, respectively) affected the size or level of synthesis of the urease subunits as monitored by polyacrylamide gel electrophoresis. The wild type enzyme and each of the mutant proteins was purified and their properties were compared. The C319Y protein possessed no detectable activity, while activity was reduced in C319A, C319S, and C319D to 48, 4.5, and 0.03% of wild type levels under normal assay conditions. All of the active mutants had a small increase in Km when compared to the wild type value. The active mutants displayed a greatly reduced sensitivity to inactivation by iodoacetamide in comparison to the wild type enzyme, confirming our previous assignment of the essential cysteine to this residue based on active site peptide mapping. In contrast to the wild type enzyme, inactivation of the mutant proteins was not affected by the presence of the competitive inhibitor phosphate, suggesting that the remaining slow rate of iodoacetamide inactivation is due to modification away from the active site. The pH dependence of urease activity was substantially altered in the active mutants with C319S and C319D showing a pH optimum near 5.2, and C319A near 6.7, compared to the pH 7.75 optimum of wild type urease. These data are consistent with Cys-319 facilitating catalysis at neutral and basic pH values by participating as a general acid.
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PMID:Site-directed mutagenesis of the active site cysteine in Klebsiella aerogenes urease. 140 Mar 17

The middle base (U35) of the anticodon of tRNA(Gln) is a major element ensuring the accuracy of aminoacylation by Escherichia coli glutaminyl-tRNA synthetase (GlnRS). An opal suppressor of tRNA(Gln) (su+2UGA) containing C35 (anticodon UCA) was isolated by genetic selection and mutagenesis. Suppression of a UGA mutation in the E. coli fol gene followed by N-terminal sequence analysis of purified dihydrofolate reductase showed that this tRNA was an efficient suppressor that inserted predominantly tryptophan. Mutations of the 3-70 base pair (U70 and A3U70) were made. These mutants of su+2UGA are less efficient suppressors and inserted predominantly tryptophan in vivo; alanine insertion was not observed. Mutations of the discriminator nucleotide (A73, U73, C73) result in very weak opal suppressors. Aminoacylation in vitro by E. coli TrpRS of tRNA(Gln) transcripts mutated in the anticodon demonstrate that TrpRS recognizes all three nucleotides of the anticodon. The results show the interchangeability of the glutamine and tryptophan identities by base substitutions in their respective tRNAs. The amber suppressor (anticodon CUA) tRNA(Trp) was known previously to insert predominantly glutamine. We show that the opal suppressor (anticodon UCA) tRNA(Gln) inserts mainly tryptophan. Discrimination by these synthetases for tRNA includes position 35, with recognition of C35 by TrpRS and U35 by GlnRS. As the use of the UGA codon as tryptophan in mycoplasma and in yeast mitochondria is conserved, recognition of the UCA anticodon by TrpRS may also be maintained in evolution.
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PMID:Switching tRNA(Gln) identity from glutamine to tryptophan. 156 39

The nucleotide sequences of the complete set of tRNA species in Mycoplasma capricolum, a derivative of Gram-positive eubacteria, have been determined. This bacterium represents the first genetic system in which the sequences of all the tRNA species have been determined at the RNA level. There are 29 tRNA species: three for Leu, two each for Arg, Ile, Lys, Met, Ser, Thr and Trp, and one each for the other 12 amino acids as judged from aminoacylation and the anticodon nucleotide sequences. The number of tRNA species is the smallest among all known genetic systems except for mitochondria. The tRNA anticodon sequences have revealed several features characteristic of M. capricolum. (1) There is only one tRNA species each for Ala, Gly, Leu, Pro, Ser and Val family boxes (4-codon boxes), and these tRNAs all have an unmodified U residue at the first position of the anticodon. (2) There are two tRNAThr species having anticodons UGU and AGU; the first positions of these anticodons are unmodified. (3) There is only one tRNA with anticodon ICG in the Arg family box (CGN); this tRNA can translate codons CGU, CGC and CGA. No tRNA capable of translating codon CGG has been detected, suggesting that CGG is an unassigned codon in this bacterium. (4) A tRNATrp with anticodon UCA is present, and reads codon UGA as Trp. On the basis of these and other observations, novel codon recognition patterns in M. capricolum are proposed. A comparatively small total, 13, of modified nucleosides is contained in all M. capricolum tRNAs. The 5' end nucleoside of the T psi C-loop (position 54) of all tRNAs is uridine, not modified to ribothymidine. The anticodon composition, and hence codon recognition patterns, of M. capricolum tRNAs resemble those of mitochondrial tRNAs.
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PMID:Codon recognition patterns as deduced from sequences of the complete set of transfer RNA species in Mycoplasma capricolum. Resemblance to mitochondria. 247 13

Increased brain and plasma glutamine after ammonia inhalation had an effect on the concentrations of selected amino acids in rats. Rats inhaled ammonia vapour of 25 and 300 p.p.m. for 5 days 6 hr daily. Brain glutamine increased from the control level, 10.9 +/- 2.6 (S.D.) mumol/g to 15.5 +/- 5.2 (S.D.) mumol/g (P less than 0.05) in 25 p.p.m. NH3 and to 15.3 +/- 1.1 (S.D.) mumol/g (P less than 0.01) in 300 p.p.m. NH3. The blood glutamine was also increased so that the brain/plasma ratio was not changed. A slight elevation in the brain threonine was found, from 0.6 +/- 0.1 (S.D.) mumol/g (controls) to 0.8 +/- 0.2 (S.D.) mumol/g in 25 p.p.m. and to 0.8 +/- 0.1 (S.D.) mumol/g in 300 p.p.m. NH3. The brain/plasma ratio of threonine was increased at the 300 p.p.m. level. The increasing brain threonine linearly correlated to the increased plasma glutamine the general correlation co-efficient being 0.59 according to a linear regression analysis. The effects on other amino acids, e.g., glycine, alanine, serine, aspartate, glutamate, were less clear. It seems that the elevated blood glutamine impaired the threonine export or augmented its uptake from the blood stream. Exposure to NH3 vapour by inhalation proved to be an alternative model to portocaval shunting or urease injections in the study of hyperammonemia in the brain.
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PMID:Effect of short-term ammonia inhalation on selected amino acids in rat brain. 272 87

Succinivibrio dextrinosolvens C18 was found to possess glutamine synthetase (GS), urease, glutamate dehydrogenase, and several other nitrogen assimilation enzymes. When grown in continuous culture under ammonia limitation, both GS and urease activities were high and glutamate dehydrogenase activity was low, but the opposite activity pattern was observed for growth in the presence of ample ammonia. The addition of high-level (15 mM) ammonium chloride to ammonia-limited cultures resulted in a rapid loss of GS activity as measured by either the gamma-glutamyl transferase or forward assay method with cells or extracts. No similar activity losses occurred for urease, glutamate dehydrogenase, or pyruvate kinase. The GS activity loss was not prevented by the addition of chloramphenicol and rifampin. The GS activity could be recovered by washing or incubating cells in buffer or by the addition of snake venom phosphodiesterase to cell extracts. Manganese inhibited the GS activity (forward assay) of untreated cells but stimulated the GS activity in ammonia-treated cells. Alanine, glycine, and possibly serine were inhibitory to GS activity. Optimal pH values for GS activity were 7.3 and 7.4 for the forward and gamma-glutamyl transferase assays, respectively. The glutamate dehydrogenase activity was NADPH linked and optimal in the presence of KCl. The data are consistent with an adenylylation-deadenylylation control mechanism for GS activity in S. dextrinosolvens, and the GS pathway is a major route for ammonia assimilation under low environmental ammonia levels. The rapid regulation of the ATP-requiring GS activity may be of ecological importance to this strictly anaerobic ruminal bacterium.
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PMID:Glutamine synthetase activity in the ruminal bacterium Succinivibrio dextrinosolvens. 286 38

Several commercially available enzymes were tested for their ability to hydrolyze amino acid carbamates. No activity was found with pig liver esterase, the hydantoinase from Pseudomonas fluorescens DSM 84, or the urease from jack beans. A stereoselective cleavage of the carbamyl group yielding L-amino acids was observed by acylase and acetylcholinesterases from bovine and human erythrocytes. Racemic mixtures of N-(methoxycarbonyl)-DL-alanine, N-(ethoxycarbonyl)-DL-alanine, and the corresponding valine carbamates are hydrolyzed to L-alanine and L-valine, respectively, by acylases leaving the D-amino acid carbamates unchanged. The lysine carbamates were not hydrolyzed by acylases. In contrast only the methoxycarbonyl amino acids were split by acetylcholinesterases, which, however, also cleave alpha, epsilon-(N-methoxycarbonyl)-DL-lysine stereoselectively at the alpha position, yielding epsilon-N-methoxycarbonyl-L-lysine. The optimum pH for enzymatic activity of hog kidney acylase was 7.5 and a Km value of 8.2 mM for N-(methoxycarbonyl)-DL-alanine was determined. For the acetylcholinesterases the reaction rate reaches an optimum between pH 7.5 and 8. The Km value was 68 mM for N-(methoxycarbonyl)-DL-alanine.
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PMID:Studies on the enzymatic hydrolysis of amino acid carbamates. 311 96


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