Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of fluphenazine and related phenothiazine and thioxanthene derivatives on beef heart soluble mitochondrial ATPase (EC 3.6.1.3) was studied under a precise control of the Mg2+-ATP equilibrium. These drugs were shown to be reversible, noncompetitive inhibitors with respect to the substrate (the Mg . ATP complex). The inhibition was found to be dependent on the concentration of free magnesium ions, although free Mg2+ was not essential for the interaction of the inhibitors with the enzymatic protein. Bicarbonate anions, which are known to antagonize the effect of free Mg2+ on the enzyme kinetics, also antagonized the drug-induced inhibition. Concentrations giving 50% inhibition of enzyme activity were in the micromolar range. Inhibitory potencies increased when the pH of the reaction mixture was lowered from 8.2 to 6.9. Cleland [The Enzymes (P. D. Boyer, ed.), Vol. II. Academic Press, New York, 1--65 (1970)] analysis of the inhibition, by means of slope and intercept replots, indicated that the inhibition was the result of the interaction with more than one drug molecule. All drugs tested afforded complete protection against the cold-induced inactivation of soluble mitochondrial ATPase. These results point to a specific mode of inhibition that mimics, in some respects, the action of the natural inhibitor protein of mitochondrial ATPase.
 ...
PMID:Magnesium-dependent inhibition of beef heart soluble mitochondrial adenosine triphosphatase by tricyclic antipsychotics. 612 79

The binding of "oligomycin sensitivity conferring protein" (OSCP) to soluble beef-heart mitochondrial ATPase (F1) has been investigated. OSCP forms a stable complex with F1, and the F1 X OSCP complex is capable of restoring oligomycin- and DCCD-sensitive ATPase activity to F1- and OSCP-depleted submitochondrial particles. The F1 X OSCP complex retains 50% of its ATPase activity upon cold exposure while free F1 is inactivated by 90% or more. Both free F1 and the F1 X OSCP complex release upon cold exposure a part--probably 1 out of 3--of their beta subunits; whether alpha subunits are also lost is uncertain. The cold-treated F1 X OSCP complex is still capable of restoring oligomycin- and DCCD-sensitive ATPase activity to F1- and OSCP-depleted particles. OSCP also protects F1 against modification of its alpha subunit by mild trypsin treatment. This finding together with the earlier demonstration that trypsin-modified F1 cannot bind OSCP indicates that OSCP binds to the alpha subunit of F1 and that F1 contains three binding sites for OSCP. The results are discussed in relation to the possible role of OSCP in the interaction of F1 with the membrane sector of the mitochondrial ATPase system.
 ...
PMID:The oligomycin sensitivity conferring protein (OSCP) of beef heart mitochondria: studies of its binding to F1 and its function. 624 46

We have found that when the ATP hydrolysis activity of beef heart mitochondrial adenosine triphosphatase (F1) is eliminated by either cold treatment or chemical modification, the enzyme attains the ability to catalyze the Pi in equilibrium ATP exchange reaction. The ATP hydrolysis activity of isolated F1 was lost upon chemical modification by phenyglyoxal, butanedione, or 7-chloro-4-nitrobenzene-2-oxa-1,3-diazole. The F1 thus chemically modified was able to catalyze an ADP-dependent Pi in equilibrium ATP exchange reaction. In addition F1 that had been cold-treated to eliminate ATP hydrolysis activity, also catalyzed the Pi in equilibrium ATP exchange reaction. The Pi in equilibrium ATP exchange catalyzed by modified F1 was shown to be totally inhibited by the F1-specific antibiotic efrapeptin. We have previously shown that isolated beef heart mitochondrial ATPase will catalyze the formation of a transition state analog of the ATP synthesis reaction (Bossard, M. J., Vik, T. A., and Schuster, S. M. (1980) J. Biol. Chem. 255, 5342-5346). While the F1-catalyzed ATP hydrolysis activity was lost rapidly upon chemical modification or cold treatment, the ability of the enzyme to produce Pi . adenosine 5'-diphosphate (chromium(III) salt) from phosphate and monodentate adenosine 5'-diphosphate (chromium(III) salt) was unimpaired. The implications of these data with regard to the mechanism of ATP synthesis are discussed.
 ...
PMID:Catalysis of partial reactions of ATP synthesis by beef heart mitochondrial adenosine triphosphatase. 645 Jul 58

Treatment of isolated factor F1 by 1% dimethylsuberimidate in the presence of 50 mM (NH4)2SO4 leads to the formation of four different types of cross-linked dimers of the subunits, on average one dimer per molecule of the enzyme. This treatment results in 60-70% inactivation of factor F1. Factor F1 treated with dimethylsuberimidate does not show a change in the sedimentation coefficient and is not inactivated in the cold; it is not inactivated in the presence of Mg2+ either, nor is it activated by anions. Incubation of the cross-linked factor F1 with ADP does not lead to inactivation, although the ability to tightly bind ADP is retained. The total quantity of tightly bound ADP reaches 5 mol per mol of the cross-linked factor F1. Cross-linking of factor F1 also prevents the slow inactivation of the enzyme coupled with the hydrolysis of Mg-ATP and Mg-GTP. The dependence of the inactivation rate constant on the concentration of Mg-ATP and Mg-GTP at substrate concentrations of 0.05-2 mM is characterized by the same values of Km,app as those of the ATPase and GTPase activities of factor F1. The probability of the inactivation of factor F1 per turnover remains constant for all the concentrations of the substrates studied and is 2 . 10(-6) per turnover for the ATPase reaction and 2 . 10(-5) per turnover for the GTPase reaction. Moderate hydrostatic pressure (up to 150 atmospheres) greatly accelerates ATP-induced inactivation of factor F1. The activation volume (delta V*) of the inactivation process is equal to 5.1 . 10(-4) cm3/g, which is evidence of considerable changes in the extent of protein hydration during inactivation. Inactivation of the enzyme under pressure is accompanied by dissociation into subunits. Dimethyladipimidate, which does not cause intersubunit cross-linking in the molecule of factor F1, does not alter the properties of the native enzyme. It is suggested that the formation of one intersubunit cross-link in the molecule of factor F1 by dimethylsuberimidate affects the ability of the enzyme to undergo co-operative rearrangements of the quaternary structure under the influence of Mg2+, ADP, ATP, anions, and low temperature. The rate constants of ATP binding to the active site of factor F2 (k+1) = 2 . 10(8) M-1 . min-1), of ATP release from the active site (k-1 = 2 . 10(-2) min-1), and of ADP and Pi release from the active site (k2 = 5 . 10(3) min-1) have been determined. The results obtained confirm the correctness of Boyer's idea, according to which ATP is formed in the active site of mitochondrial ATPase without any external source of energy. Energy is used at the stage of the release of synthesized ATP from the active site of ATPase in the solution.
 ...
PMID:Structural rearrangements in soluble mitochondrial ATPase. 645 13

The isolation and properties of F1-mitochondrial ATPase from rat testis are described. The isolation medium involves a chloroform extraction, and it is suitable even with small amounts of starting material that have a relatively low specific activity as in the case of rat testis submitochondrial particles. The isolated enzyme from rat testis had a specific activity of 30-45 mumol Pi/min/mg protein, which could be increased up to 90 mumol Pi/min/mg protein only in the presence of bicarbonate and maleate. The isolated enzyme represented less than 0.6% of the initial membrane proteins. It exhibited a typical five-band pattern in sodium dodecyl sulfate gel electrophoresis. However, it showed a ratio of subunits alpha:beta higher than the heart enzyme; its significance is unknown. The purified enzyme was cold labile and inhibited by natural ATPase inhibitor protein from bovine heart mitochondria and by dicyclohexylcarbodiimide. The results presented suggest that the low ATPase activity of testis submitochondrial particles is due to a reduced content of the F1-ATPase.
 ...
PMID:Isolation and comparative studies of mitochondrial F1-ATPase from rat testis and beef heart. 911 89

Cellular responses to cold stress have not been well clarified, compared with heat shock responses, especially in mammalian cells. We investigated cold-stress responses in human hepatoblastoma cells (HepG2) exposed to a nonfatal temperature of 17 degrees C. Under the condition, RNA and protein syntheses in the cells were highly, but incompletely, depressed and cell growth was impaired. A cDNA subtraction method was used to isolate mRNAs for which the levels were increased in cold-stressed cells compared with cells cultured at 37 degrees C. A transcript isolated by the screening was identified as ATPase subunit 6+8 mRNA that encodes components of a mitochondrial ATPase complex and that is transcribed from a mitochondrial genome. The copy number of the mitochondrial genome in cells was not changed by cold stress. Thus, HepG2 cells were treated with various concentrations of actinomycin D and chloramphenicol to assess the effects of transcriptional and translational reduction on the increased level of the ATPase subunit 6+8 mRNA. The mRNA level was increased in cells treated with low concentrations of the RNA or protein synthesis inhibitors. These results indicate that the increase in ATPase subunit 6+8 mRNA stimulated by cold stress could be mediated by a partial decline of transcription and/or translation in the cells. In addition, the degradation of ATPase subunit 6+8 mRNA was suppressed in cold-stressed cells compared with that in 37 degrees C-cultured cells. This result implies that posttranscriptional regulation is also involved in the cold-stimulated increase in ATPase subunit 6+8 mRNA in HepG2 cells.
 ...
PMID:Mitochondrial genome-encoded ATPase subunit 6+8 mRNA increases in human hepatoblastoma cells in response to nonfatal cold stress. 1078 8

The membrane-associated Mg(2+)-activated and Ca(2+)-activated adenosine 5'-triphosphatase (EC 3.6.1.3; ATPase) activities of Escherichia coli were further characterized. The degree of inhibition of membrane-bound Mg(2+)-(Ca(2+))-ATPase by a series of anions (i.e., sodium salts of nitrate, iodide, chloride, and acetate) was found to correlate with the relative chaotropic, or solubilizing, effectiveness of these anions. The enzyme was solubilized from washed membrane ghosts by treatment with 0.04% sodium lauryl sulfate at pH 9.0 and 37 C. Solubilized Mg(2+)-(Ca(2+))-ATPase exhibited an initial increase in activity, followed by fairly rapid inactivation, both ATPase activities being particularly cold-labile. The combined stabilizing effects of lauryl mercaptan (1-dodecanethiol), 0.01 m tris(hydroxymethyl)amino-methane-hydrochloride buffer (pH 9.0), 0.2 mm MgCl(2), and ambient temperature facilitated partial purification of the enzyme, the molecular weight of which was estimated to be approximately 100,000 by the gel filtration technique. In general, the membrane-associated Mg(2+)-(Ca(2+))-ATPase of E. coli resembles both mitochondrial membrane ATPase and the well-characterized membrane ATPases of Bacillus megaterium and Microcococcus lysodeikticus. It is of particular interest that N,N'-dicyclohexylcarbodiimide (DCCD), a known inhibitor of mitochondrial ATPase, of mitochondrial oxidative phosphorylation, and of the membrane-bound Mg(2+)-ATPase of Streptococcus faecalis was found to inhibit both the membrane-bound and the solubilized forms of E. coli Mg(2+)-(Ca(2+))-ATPase. The sensitivity of the membrane-associated Mg(2+)-(Ca(2+))-ATPase of E. coli to both anions and cations, its allotopic behavior, and its susceptibility to inhibition by DCCD favor the idea that this enzyme plays a key, probably polyfunctional, role in such biological activities of the membrane as oxidative phosphorylation and ion transport.
 ...
PMID:Membrane Mg-(Ca)-Activated Adenosine Triphosphatase of Escherichia coli: Characterization in the Membrane-Bound and Solubilized States. 1655 94


<< Previous 1 2