UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was discovered that the product of a mix containing the enzyme creatine phosphokinase (CPK) and either glutathione (GSH) or cysteine caused platelets to adhere together in vitro. This platelet adhesive factor (PAF) was formed as CPK enzyme activity declined. An alternative method for the destruction of enzyme activity--heat at 56 degrees C--also resulted in the formation of an in-vitro active PAF which was both less stable and active than its chemically produced counterpart. Assay of the platelet adhesive potency of the CPK-GSH mix, using human platelets, revealed a wide variation in the response of different individuals' platelets to standard quantities of PAF. The nature of this preparation of PAF was investigated by both biochemical and biophysical means, including ion exchange chromatography, electrophoresis, amino acid analysis and analytical ultracentrifuge studies. Evidence is presented that PAF is the product of the disruption of the dimeric structure of the CPK molecule. PAF was found to adhere to paper, under the conditions of electrophoresis imposed, and also to cause sephadex beads to bind together, characteristics which suggested that the platelet adhesion reaction was probably a biophysical process. Red and white cells were not similarly affected. The feasibility of this novel concept for the initiation of platelet adhesion, as a naturally occurring process, was supported by the results of animal experiments in which a statistically depression of platelets in the systemic circulation followed the intravascular administration of PAF. The possible relevance to man of this basic mechanism in relation to exercise and disease processes, including ideopathic and post-traumatic thrombosis, atherogenesis, and dysbaric aseptic necrosis of bone, is discussed.
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PMID:The formation of a platelet adhesive factor by disruption of the creatine phosphokinase molecule. 1 Mar 63

The trace metals nickel and platinum, which are not substrates for ferrochelatase and thus do not form heme in biological systems, were found to act similaryl to cobalt, and heme itself, in regulating heme metabolism in liver and kidney. These metals induced heme oxygenase activity in both organs with the peak of induced enzyme activity reached approximately 16 hr after single injections in rats. Both metals caused transient depression of cellular glutathione content followed by increases above normal after 12 hr in liver. Nickel and platinum were more potent inducers of heme oxygenase in kidney than in liver (10-13 times normal versus 5-6 times normal). At high concentrations, they inhibited heme oxygenase [heme, hydrogen-donor:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating), EC 1.14.99.3] in vitro. Both were active in regulating heme metabolism only when administered in the ionic form. Complexing of the metals with sulfhydryl agents completely blocked their actions on heme metabolism. Administration of cysteine orally prior to or shortly after administration of the metals had a similar blocking effect. Nickel and platinum produced depression of delta-aminolevulinate synthase [succinyl-CoA:glycine c-succinyltransferase (decarboxylating), EC 2.3.1.37] activity in liver, but neigther inhibited this rate-limiting ennzyme for heme synthesis in vitro. Furthermore, despite the substantial decreases in cellular heme and hemoprotein contents mediated by the metal, production of delta-amimolevulinate synthase did not undergo the compensatory increase that would be expected if there were a direct reciprocal feedback relationship between cellular heme level and synthesis of this enzyme. These findings indicate that it is not necessary for metal ions to be chelated in the porphyrin ring in order to regulate the enzymes of heme synthesis and heme oxidation. Accordingly, it is suggested that the iron atom of heme is the proximately active regulator of delta-aminolevulinate synthase and heme oxygenase--actions generally ascribed to the iron-tetrapyrrole complex itself--and that the tetrapyrrole moiety of the complex functions primarily as a means of transport of the metal to regulatory sites in cells.
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PMID:Regulation of heme pathway enzymes and cellular glutathione content by metals that do not chelate with tetrapyrroles: blockade of metal effects by thiols. 26 10

The effects of N-ethylmaleimide (NEM), a sulfhydryl blocking reagent, on the membrane currents, action potentials and contractile tension in bullfrog atrial muscle were studied by using the double sucrose gap technique. In concentrations of 10(-3) to 10(-4) M, NEM led to a transient enhancement of twitch contraction followed by a late inhibition, while 10(-2) M NEM merely produced an inhibitory effect. The positive inotropism was accompanied by a prolongation of action potential and the negative inotropism, by a depression of action potential. Under voltage clamp conditions, 10(-3) M NEM reduced the fast inward current and increased the steady state outward and background currents. The slow inward current and the inward Ca current in Na-free conditions were transiently increased by 10(-3) M NEM with an enhancement of contractile tension. In voltage-tension relationships, NEM-induced augmentation of tension appeared in depolarizing pulses of 60--70 mV. The results indicate that NEM increases transiently the Ca conductance of the cell membrane. Preincubation with L-cysteine blocked the production of positive inotropic effect by NEM, suggesting that the effects of NEM are due to the blockade of protein sulfhydryl group in the atrial muscle.
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PMID:The action of N-ethylmaleimide on the membrane currents and contractile tension in the bullfrog atrium. 31 65

Kinetics of the transport systems common for entry of L-isoleucine, L-leucine, and L-valine in Salmonella typhimurium LT2 have been analyzed as a function of substrateconcentration in the range of 0.5 to 45 muM. The systems of transport mutants, KA203 (ilvT3) and KA204 (ilvT4), are composed of two components; apparent Km values for uptake of isoleucine, leucine, and valine by the low Km component are 2 muM, 2 to 3 muM, and 1 muM, respectively, and by the high Km component 30 muM, 20 to 40 muM, and 0.1 mM, respectively. The transport system(s) of the wild type has not been separated into components but rather displays single Km values of 9 muM for isoleucine, 10 muM for leucine, and 30 muM for valine. The transport activity of the wild type was repressed by L-leucine, alpha ketoisocaproate, glycyl-L-isoleucine, glycyl-L-leucine, and glycyl-L-methionine. That for the transport mutants was repressed by L-alanine, L-isoleucine, L-methionine, L-valine, alpha-ketoisovalerate, alpha-keto-beta-methylvalerate, glycyl-L-alanine, glycyl-L-threonine, and glycyl-L-valine, in addition to the compounds described above. Repression of the mutant transport systems resulted in disappearance of the low Km component for valine uptake, together with a decrease in Vmax of the high Km component; the kinetic analysis with isoleucine and leucine as substrates was not possible because of poor uptake. The maximum reduction of the transport activity for isoleucine was obtained after growing cells for two to three generations in a medium supplemented with repressor, and for the depression, protein synthesis was essential after removal of the repressor. The transport activity for labeled isoleucine in the transport mutant and wild-type strains was inhibited by unlabeled L-alanine, L-cysteine, L-isoleucine, L-leucine, L-methionine, L-threonine, and L-valine. D-Amino acids neither repressed nor inhibited the transport activity of cells for entry of isoleucine.
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PMID:Repression and inhibition of transport systems for branched-chain amino acids in Salmonella typhimurium. 32 Jan 86

A technique based on resistance to azaserine was used to isolate mutants lacking O-acetylserine sulfhydrylase B, one of two enzymes in Salmonella typhimurium capable of synthesizing L-cysteine from O-acetyl-L-serine and sulfide. The mutant locus responsible for this defect has been designated cysM, and genetic mapping suggests that cysM is very close to and perhaps contiguous with cysA. Strains lacking either O-acetylserine sulfhydrylase B or the second sulfhydrylase, O-acetylserine sulfhydrylase A (coded for by cysK), are cysteine prototrophs, but cysK cysM double mutants were found to require cysteine for growth. O-Acetylserine sulfhydrylase B was depressed by growth on a poor sulfur source, and depression was dependent upon both a functional cysB regulatory gene product and the internal inducer of the cysteine biosynthetic pathway, O-acetyl-L-serine. Furthermore, a cysBc strain, in which other cysteine biosynthetic enzymes cannot be fully repressed by growth on L-cystine, was found to be constitutive for O-acetylserine sulfhydrylase B as well. Thus O-acetylserine sulfhydrylase B is regulated by the same factors that control the expression of O-acetylserine sulfhydrylase A and other activities of the cysteine regulon. It is not clear why S. typhimurium has two enzymes whose physiological function appears to be to catalyze the same step of L-cysteine biosynthesis.
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PMID:Regulation of O-acetylserine sulfhydrylase B by L-cysteine in Salmonella typhimurium. 38 18

The effect of taurine, of some of its precursors and major metabolic products on spontaneous locomotor activity were studied in mice. The effect of taurine and some analogues on certain ethanol-mediated responses were observed. Administration of taurine, 50 mg/kg, IP, did not significantly alter motility in experimental animals compared to controls. Behavioral depression was evident subsequent to injection of cysteine hydrochloride or taurocholic acid (50 mg/kg). Administration of taurocholic acid, 50 mg/kg, IP, 30 min prior to a narcotic dose of ethanol, 5 g/kg, IP, reduced the time required for the onset of ethanol-narcosis. Pretreatment with cysteic acid, 50 mg/kg, IP, prolonged ethanol-produced narcosis. Treatment with cysteic acid 30 min prior to ethanol, 2.5 g/kg, IP, was found to decrease whole blood ethanol concentration as compared to the respective controls without a concomitant changes in brain ethanol levels. Administration of taurocholic acid, 100 mg/kg, IP, decreased the intake of an ethanol solution in rats preferring 5% ethanol solution over water as the drinking fluid of choice. None of the compounds tested altered endogenous specific activity of mouse liver alcohol dehydrogenase when given once daily (50 mg/kg, IP) for 10 consecutive days. The results suggest that both taurocholic acid and cysteic acid exert additive action to some ethanol-elicited responses studied.
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PMID:Taurine, analogues and ethanol elicited responses. 48 15

In addition to an assimilatory sulfite reductase, studies of cultures of Clostridium pasteurianum supplemented with methionine, cysteine, and 35SO42- provides evidence for another reductase which is induced by SO32-. This inducible reductase appears to be dissimaltory because of the copious sulfide production arising when the cells are grown on SO32-. Cysteine can repress the assimilatory sulfite reductase but does not affect the inducible reductase. During late logarithmic growth on 1 mM SO42- + 10mM cysteine, depression of the inducible reductase occurred along with increased sulfide production. The presence of 1 mM cysteine and (or) 1 mM cysteine and (or) 1 mM methionine does not affect the inverse sulfur isotope effect for evolved H2S. However, 5 and 10 mM cysteine reduce the maximum delta34S value for released H2S from +40 to 10%. A small conversion of cysteine to H2S by C. pasteurianum occurs, but only in the stationary phase.
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PMID:Stable isotope fractionation by Clostridium pasteurianum. 2. Regulation of sulfite reductases by sulfur amino acids and their influence on sulfur isotope fractionation during SO32- and SO42- reduction. 66 38

Similar depressions in growth were observed when rats consumed a 10% casein basal diet containing equal quantities of either methionine or S-methyl-L-cysteine. Supplemental glycine or serine partially alleviated the growth depression caused by the high levels of methionine but were ineffective in alleviating the growth depression caused by high levels of S-methylcysteine. Histological examination of five organs of rats fed the basal, high methionine or high S-methylcysteine diet for 6, 13 or 20 days revealed that only the spleens were affected in that there was erythrocyte engorgement and an accumulation of hemosiderin. The intensity of iron staining in spleens decreased from the second to the third week. The similarity in the depression of growth and splenic damage observed in rats consuming high levels of methionine or S-methylcysteine is consistent with an earlier suggestion that metabolism of the methionine or S-methylcysteine is consistent with an earlier suggestion that metabolism of the methyl group is in some way involved in the toxicity of methionine.
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PMID:Growth depression and tissue reaction to the consumption of excess dietary methionine and S-methyl-L-cysteine. 99 52

Experiments were performed on the isolated rabbit hearts and also on the hearts with complete atrioventricular block; a study was made of the effect of an excess or deficiency of the sulfhydryl groups on the automatism of the cardiac pace makers. Unithiol and cysteine in concentrations of 1-10(-6)-1-10(-4) g/ml were used as donors of sulfhydryl groups; deficiency of these groups was induced by the alloxan administration in concentrations of 1-10(-5)-5-10(-5) g/ml. Changes in the sulfhydryl group content produced no marked effect on the automatism of the synoatrial node. An excess of sulfhydryl groups promoted poststimulation depression of the automatism of the potential pace makers of the cardiac ventricles and could lead to the origination of Luciani's periods. On the contrary, in case of a deficiency of the sulfhydryl groups there was a sharp elevation of the automatism of the ventricular pace makers, the atrioventricular conduction became disturbed, and the poststimulation depression of the automatism became considerably diminished. Disturbances of the cardiac activity caused by the sulfhydryl group deficiency were completely eliminated by unithiol or cysteine.
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PMID:[Effect of sulfhydryl compounds on the automatism of the pacemakers]. 102 91

This study was undertaken to examine the effects of oxygen free radicals on mitochondrial creatine kinase activity in rat heart. Xanthine plus xanthine oxidase (superoxide anion radical generating system) reduced mitochondrial creatine kinase activity both in a dose- and a time-dependent manner. Superoxide dismutase showed a protective effect on depression in creatine kinase activity due to xanthine plus xanthine oxidase. Hydrogen peroxide inhibited creatine kinase activity in a dose-dependent manner, this inhibition was protected by the addition of catalase. In order to understand the detailed mechanisms by which oxygen free radicals inhibit mitochondrial creatine kinase activity, the effects of oxygen free radicals on mitochondrial sulfhydryl groups were examined. Mitochondrial sulfhydryl groups contents were decreased by xanthine plus xanthine oxidase or hydrogen peroxide; this depression in sulfhydryl groups contents was prevented by the addition of superoxide dismutase or catalase. N-Ethylmaleimide (sulfhydryl group reagent) expressed inhibitory effects on the creatine kinase activity both in a dose- and a time-dependent manner; dithiothreitol or cysteine (sulfhydryl group reductant) showed protective effects on the creatine kinase activity depression induced by N-ethylmaleimide. Dithiothreitol or cysteine also blocked the depression of mitochondrial creatine kinase activity caused by xanthine plus xanthine oxidase or hydrogen peroxide. These results lead us to conclude that oxygen free radicals may inhibit mitochondrial creatine kinase activity by modifying sulfhydryl groups in the enzyme protein.
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PMID:Decrease in heart mitochondrial creatine kinase activity due to oxygen free radicals. 132 80

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