Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several structural analogues of GABA were shown to be inhibitors of GABAA receptor binding in membranes from cat cerebral cortex. These compounds were 3-aminopropanesulfonic acid (APS; IC50 = 0.04 microM), imidazoleacetic acid (IMA; IC50 = 0.4 microM), morpholinopropanesulfonic acid (MOPS; IC50 = 1.6 microM), 5-phenylpyrrolepropionic acid (PPP; IC50 = 15 microM), aminoethanethiosulfonic acid (AETS; IC50 = 22 microM), 3-amino-3-phenylpropionic acid (APP; IC50 = 35 microM), meta-aminobenzoic acid (MABA; IC50 = 58 microM) and urocanic acid (UCA; IC50 = 354 microM). The IC50 value for GABA was 0.03 microM. GABA, PPP, AETS, MABA and UCA were previously shown to reduce arterial pressure in the cat after intracerebroventricular infusion. In the present study MOPS (ED50 = 0.26 nmol/kg), APS (ED50 = 4.7 nmol/kg), APP (ED50 = 49 nmol/kg), and IMA (ED50 = 350 nmol/kg) were also found to be able to decrease blood pressure when infused into the fourth ventricle. All nine compounds reduced blood pressure to the same extent, but in some cases their relative potencies (ED50 values) exhibited significant differences. When the IC50 values for receptor binding were plotted against the ED50 values for the cardiovascular effects, no significant correlation emerged. This lack of a correlation does not necessarily imply that the reductions in blood pressure elicited by the drugs are not related to an activation of central GABAA receptors. Instead, it highlights the difficulties that are sometimes encountered in attempting to obtain quantitative measurements after intracerebroventricular infusion.
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PMID:Central receptor binding and cardiovascular effects of GABA analogues in the cat. 303 35

A previous study of the patterns of visual evoked responses (VERs) in rats was interpreted as providing support for the synergistic neurotoxins hypothesis of the pathogenesis of hepatic encephalopathy (HE) due to fulminant hepatic failure (FHF). In contrast, other studies of the patterns of VERs in rabbits with different encephalopathies were interpreted as providing support for the concept that increased GABA-ergic tone may contribute to the neural inhibition of HE due to FHF. To attempt to resolve the discordant findings in these studies, additional studies of VERs have been undertaken in rats. To induce increased tissue levels of ammonia, mercaptans and fatty acids which are found in HE due to FHF, carefully predetermined doses of urease, dimethyldisulphide and octanoic acid were administered. The (pre-seizure) encephalopathy induced by these three agents was associated with abnormalities of the VER waveform that were fundamentally different from the abnormalities of the VER waveform associated with HE due to thioacetamide-induced FHF. However, the VER waveform in this model of HE due to FHF resembled closely that associated with pentobarbital-induced encephalopathy. These findings are in satisfactory agreement with those in the previous analogous studies in rabbits. They do not provide support for the synergistic neurotoxins hypothesis of the pathogenesis of HE, but are entirely consistent with increased GABA-ergic tone contributing to the neural inhibition of HE due to FHF.
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PMID:Hepatic encephalopathy. Application of visual evoked responses to test hypotheses of its pathogenesis in rats. 303 57

To examine the rate-of-living theory, age-related changes in amino acid pool sizes were investigated in the adult silkmoth, Bombyx mori, reared at low and high temperature. At either temperature concentrations of free amino acids contained in silkmoths revealed a great sexual difference. Those in females were generally much higher than in males and the former changed much more dynamically than the latter. Major amino acids or ninhydrin-positive compounds inclusive of some essential amino acids such as Leu, Ile, Val, Thr, Arg, Phe, Met, Ala, Tyr, Gln, Aspn , Lan , Cysta , GABA and PEA accumulated in 4 degrees C-moths. However, the levels of these amino changed irregularly with advanced age. Inhibition of protein synthesis may occur generally at low temperature, while protein degradation may be promoted at high temperature. High concentrations of MSO and Tau in the moths reared at high temperature than in the normal moths suggested also catabolism of amino acids proceeding together with protein degradation at high temperature. Amino acid metabolism seems to be complicated under various temperature conditions. When reared at the optimal temperature of 25 degrees C, urea is not present in the body of the silkmoth except for a slight amount in the secreted meconium. In silkmoths reared at the higher temperature of 35 degrees C, however, an extraordinary accumulation of urea occurs accompanied by a reduction in lifespan by one half. Undoubtedly, urea is produced in this terrestrial insect, although the accumulation mechanism is not clear: in silkmoths reared at various temperatures, arginase is found, but urease is not detected. Arginase activity was found to be higher in male moths than in female moths regardless of the rearing temperature. High temperature rearing also did not induce activity and female activity never exceeded that in males at either 25 degrees C or 35 degrees C rearing. Protein degradation accelerated by rearing at high temperatures may result in increased amounts of free arginine, which could cause the active production of urea. This possibility would be a counter-argument to the rate of living theory relating to longevity and temperature. However, at least the above facts signify that an extrinsic factor influences the longevity of an animal by altering its intrinsic aging process.
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PMID:Age-related changes in amino acid pool sizes in the adult silkmoth, Bombyx mori, reared at low and high temperature; a biochemical examination of the rate-of-living theory and urea accumulation when reared at high temperature. 672 18

Metabolic adaptation of Mycobacterium tuberculosis (M. tuberculosis) to microbicidal intracellular environment of host macrophages is fundamental to its pathogenicity. However, an in-depth understanding of metabolic adjustments through key reaction pathways and networks is limited. To understand how such changes occur, we measured the cellular metabolome of M. tuberculosis subjected to four microbicidal stresses using liquid chromatography-mass spectrometric multiple reactions monitoring (LC-MRM/MS). Overall, 87 metabolites were identified. The metabolites best describing the separation between stresses were identified through multivariate analysis. The coupling of the metabolite measurements with existing genome-scale metabolic model, and using constraint-based simulation led to several new concepts and unreported observations in M. tuberculosis; such as (i) the high levels of released ammonia as an adaptive response to acidic stress was due to increased flux through L-asparaginase rather than urease activity; (ii) nutrient starvation-induced anaplerotic pathway for generation of TCA intermediates from phosphoenolpyruvate using phosphoenolpyruvate kinase; (iii) quenching of protons through GABA shunt pathway or sugar alcohols as possible mechanisms of early adaptation to acidic and oxidative stresses; and (iv) usage of alternate cofactors by the same enzyme as a possible mechanism of rewiring metabolic pathways to overcome stresses. Besides providing new leads and important nodes that can be used for designing intervention strategies, the study advocates the strength of applying flux balance analyses coupled with metabolomics to get a global picture of complex metabolic adjustments.
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PMID:Rewiring of Metabolic Network in Mycobacterium tuberculosis During Adaptation to Different Stresses. 3173 86