Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of actin to heavy meromyosin (HMM) in the presence of ATP was studied by analytical ultracentrifuge and ATPase studies. At 0 degrees C, at very low ionic strength, the double-reciprocal plot of HMM ATPase against actin concentration is linear. If one assumes that all of the HMM is bound to actin when the ATPase activity equals V(max), then, at an actin concentration where the actin-HMM ATPase is 85% of V(max), all but 15% of the HMM should be complexed with actin. However, when the binding of HMM to actin in the presence of ATP was measured with the analytical ultracentrifuge, more than 60% of the HMM was not bound to actin. From experiments with EDTA- and Ca-ATPases it seemed unlikely that the unbound HMM was denatured. It is thus possible that during the steady-state hydrolysis of ATP, HMM spends more than 50% of its cycle of interaction with actin and ATP in a "refractory state," unable to bind to actin, i.e., while an HMM molecule goes through one cycle of interaction with actin and ATP, an actin monomer could bind and release several HMM molecules so that the turnover rate per mole of added actin would be considerably greater than that per mole of added HMM. Comparison of the rate of ATPase activity at very high actin concentration with that at very high HMM concentration shows that this is indeed so. Therefore, both kinetic and ultracentrifuge studies suggest that the HMM exists in a refractory state during a large part of its cycle of interaction with actin and ATP.
 ...
PMID:Heavy meromyosin: evidence for a refractory state unable to bind to actin in the presence of ATP. 425 67

1. The K and Na concentrations in red blood cells (R.B.C.) of 251 animals of the Simmenthal breed and thirty-two animals of other cattle breeds were measured. [Na](cells)+[K](cells) was 89.4 m-mole/l. cells. [K](cells) varied between 7 and 70 and [Na](cells) varied in the inverse sense between 15 and 87 m-mole/l. cells.2. The frequency distribution of animals according to K content of R.B.C.S, which could best be fitted by two superimposed Gaussian curves, suggests that there are two distinct types of cells (high K (HK) cells and low K (LK) cells). Animals with HK cells were considerably less frequent than animals with LK cells.3. Differences in breed, age or sex do not account for the difference in cation content of R.B.C.S.4. Cold stored or PCMBS-treated HK cells show a more vigorous cation pump activity than equally treated LK cells.5. At a Na concentration of 100 mM and a K concentration of 10 mM isolated haemoglobin-free membranes prepared from HK cells exhibit a higher activity of Na+K stimulated (ouabain inhibitable) ATPase activity per mg of protein than membranes from LK cells.
 ...
PMID:High potassium and low potassium erythrocytes in cattle. 426 73

We describe an abrupt increase (at 32 degrees ) in the energy of activation for the reaction of hepatic adenylyl cyclase in the presence of glucagon or epinephrine. This increase is not seen in the presence of fluoride, prostaglandin E(1), or 1-propanol, or in the absence of cyclase stimulators. The change in energy of activation found with hormones is abolished by 1-propanol. This change does not represent differences in hormone or substrate binding at different temperatures, but seems to reflect interactions among elements of the cyclase stimulation sequence. Similar changes in energy of activation were not observed for alkaline phosphatase, cyclic AMP-phosphodiesterase, 5'-nucleotidase, or ouabain-sensitive ATPase. Since the mole fraction of cholesterol in liver membranes is sufficiently high to preclude a phase change in bulk membrane lipids, our observation suggests either that cyclase is restricted to cholesterol-poor membrane regions or that the change in its energy of activation is largely restricted to protein components of the cyclase apparatus. The data are compatible with fundamental differences in the stimulation process(es) for the hormones (glucagon and epinephrine) as compared with those for fluoride and prostaglandin E(1).
 ...
PMID:A temperature-sensitive change in the energy of activation of hormone-stimulated hepatic adenylyl cyclase. 435 55

1. Spleen slices pre-incubated for different periods at 4 degrees C in Krebs solution containing varying concentrations of calcium, up to 96 mM, lost their endogenous noradrenaline stores when reincubated in normal Krebs solution at 37 degrees C for 2 hr. Rate of loss of noradrenaline was roughly related to the calcium concentration of the pre-incubation medium and the pre-exposure time.2. Pre-treatment with isotonic barium or strontium (96 mM) Krebs solution also induced release of noradrenaline from spleen slices when re-exposed to normal Krebs solution. Barium was more effective than either calcium or strontium.3. The enhanced release induced by calcium pre-treatment occurred in the absence of calcium, with or without EGTA.4. Tissue calcium concentration of spleen slices was 0.68 m-mole/kg. Pre-treatment of slices with normal or 96 mM calcium-Krebs solution for 4 hr at 4 degrees C increased the calcium concentration to 2.57 and 9.9 m-mole/kg, respectively.5. Ouabain, which caused a dose-dependent release of noradrenaline, did not modify the release induced by calcium pre-treatment.6. Spleen slices prepared from cats anaesthetized with sodium pentobarbitone instead of ether were resistant to noradrenaline depletion by calcium pre-treatment.7. Evoked release of [(3)H]noradrenaline by high potassium from calcium-pre-treated slices did not occur in the absence of external calcium, even though the calcium pre-treatment enhanced the tissue concentration of this ion by nearly tenfold.8. Net uptake of noradrenaline in normal and in treated slices whose noradrenaline content was severely reduced by barium pre-treatment or sodium withdrawal was comparable.9. Specific activity of released and endogenous [(3)H]noradrenaline increased as the tissue stores of noradrenaline were reduced.10. It is suggested that the spontaneous loss of tissue noradrenaline after pre-treatment with high-calcium solution was due to inhibition of sodium-potassium-activated ATPase by intracellular accumulation of calcium ions. Evidence is presented to suggest that vesicles depleted of their endogenous transmitter by pre-treatment with calcium, strontium or barium, or by sodium withdrawal, are re-used for the storage and release of exogenous noradrenaline.
 ...
PMID:Release of noradrenaline from slices of cat spleen by pre-treatment with calcium, strontium and barium. 477 3

The anti-tumour drug cisplatin is a potent nephrotoxic agent. Renal Na+/K+-activated and Mg2+-activated ATPases are shown to be equally sensitive to cisplatin inhibition in vitro. An aged solution of cisplatin, containing hydrolysis products, is a thousand times more inhibitory to ATPase (ID50 8.0 X 10(-7) M) than freshly made cisplatin solutions (ID50 6.5 X 10(-4) M). Chloride ion concentrations of 0-150 mM in the assay mixtures do not affect either the extent of inhibition of ATPase by cisplatin or the time required for inhibition to develop. We conclude that cisplatin reacts directly with ATPase rather than that a hydrolysis product is responsible for the inhibition. Various amino acid complexes with cisplatin were tested for their ability to inhibit ATPase. Cysteine/cisplatin in a mole ratio of 1 : 1 is completely ineffective. Mono-substituted methionine/cisplatin is more inhibitory than cisplatin alone but di-substituted methionine/cisplatin is less effective. The reason for these observations and their significance to nephrotoxicity are discussed.
 ...
PMID:The inhibition of renal ATPase by cisplatin and some biotransformation products. 612 88

The synthesis and characterisation of N-cyclohexyl-N'-(4-dimethylamino-alpha-naphthyl)carbodiimide (NCD-4) is described. Only the N-acetylurea and urea corresponding to NCD-4 are appreciably fluorescent: the O-phenylisourea and S-ethylisothiourea derivatives have negligible fluorescence. NCD-4 inhibits the (Ca2+ + Mg2+)-ATPase of sarcoplasmic reticulum irreversibly: Ca2+ protects against inhibition. Covalent incorporation of NCD-4 occurs into the Ca2+-protected sites, with a stoichiometry of approximately 1 mole/mole of ATPase. The modified enzyme has fluorescence emission properties similar to those of NCD-4 N-acetylurea in a relatively hydrophobic environment: it is concluded that NCD-4 has modified a carboxylate group (s) located in or near the Ca2+-binding sites of the ATPase.
 ...
PMID:Inactivation of sarcoplasmic reticulum (Ca2+ + Mg2+)-ATPase by N-cyclohexyl-N'-(4-dimethylamino-alpha-naphthyl)carbodiimide. 613 53

We have studied the binding of dansyl propranolol to lipid bilayers and to the (Ca2+ + Mg2+)-ATPase of sarcoplasmic reticulum. The fluorescence emission spectra for dansyl propranolol bound to the ATPase system can be fitted to the sum of three peaks, characteristic of probe bound to lipid and to protein and free in solution, respectively. Titrations show that binding to the lipid component of the ATPase system is comparable to binding to simple lipid bilayers. Binding constants obtained using fluorescence spectroscopy for binding to lipid bilayers agree with constants obtained from microelectrophoresis measurements. Binding to sites on the ATPase can be described either in terms of the aqueous concentration of dansyl propranolol or in terms of the mole fraction of dansyl propranolol in the lipid phase of the membrane. Both descriptions suggest extensive binding to annular sites at the lipid/protein interface of the ATPase. Binding at other sites on the ATPase might also be present. Binding of dansyl propranolol to the ATPase results in a marked inhibition of activity. At high Ca2+ concentrations, inhibition fits to a non-competitive model of inhibition, described by a Ki of 5 microM. We attribute this effect to binding at annular sites. At lower Ca2+ concentration, a decrease is observed in the apparent affinity of the ATPase for Ca2+ which can be attributed to a build-up of positive charge on the membrane as a result of binding.
 ...
PMID:Binding of dansyl propranolol to the (Ca2+ + Mg2+)-ATPase. 613 46

Several Ca channel blockers--verapamil, nifedipine, nimodipine (Bay e 9736), and nitrendipine (Bay e 5009)--had different effects on Ca transport by sarcoplasmic reticulum vesicles from either skeletal or cardiac muscle. Both nimodipine and nitrendipine (1 X 10(-4) M) stimulated Ca sequestration in the absence of a Ca-precipitating anion by either cardiac or skeletal sarcoplasmic reticulum (SR), with nitrendipine being the more potent stimulator. Nifedipine (1 X 10(-4)M) had no significant effect, whereas at higher concentrations (3 X 10(-3) M) verapamil inhibited the Ca sequestration reaction. Nitrendipine stimulated Ca ATPase and Ca sequestration to a similar extent. Stimulation of Ca sequestration by nitrendipine was dependent on drug/membrane phospholipid mole ratios of between 1:4 and 3:1, as well as absolute drug concentration thus suggesting an interaction of the drug with membrane phospholipids. Nifedipine, nitrendipine, nimodipine, and verapamil (1 X 10(-4)M) had no effect on phosphate-supported Ca uptake by skeletal SR, whereas higher concentrations of verapamil (3 X 10(-3)M) inhibited this reaction by either cardiac or skeletal SR. The results of this study suggest that (a) Ca channel blockers have complex and variable effects on SR membranes, (b) these effects are similar in cardiac and skeletal SR, and (c) the effects are in part mediated through an interaction with membrane phospholipids or hydrophobic portions of the Ca ATPase.
 ...
PMID:Effects of Ca channel blockers on Ca transport and Ca ATPase in skeletal and cardiac sarcoplasmic reticulum vesicles. 618 85

The binding parameters of the oligomycin-sensitivity conferring protein (OSCP) in inside-out particles from beef heart mitochondria have been tested by means of two assays, the oligomycin-sensitive ATP-Pi exchange, and the oligomycin-sensitive ATP hydrolysis. The total number of OSCP binding sites in A particles was equal to 220 pmol/mg particle protein. Each mole of ATPase active site was able to bind 1.1 +/- 0.5 mol OSCP with Kd 1.7 nM.
 ...
PMID:Titration of the binding sites for the oligomycin-sensitivity conferring protein in beef heart submitochondrial particles. 618 44

Using mixed anhydride of AMP and mesitylene carboxylic acid carrying a fluorescent or radioactive label, it was found that the previously established irreversible inhibition of myosin ATPase is a result of protein covalent binding to the nucleotide residue of the inhibitor. The stoichiometry of the affinity labelling of heavy meromyosin is 1 mole of nucleotide residue of mixed anhydride per 1 mole of protein, that of subfragment 1-0.5 mole per 1 mole of protein. The lack of irreversible inhibition of the ATPase activity of subfragment 1 is suggestive of an existence of a regulatory substrate-binding site in the myosin molecule.
 ...
PMID:[Affinity modification of heavy meromyosin and subfragment 1 by mixed anhydrides of [14C] AMP, epsilon AMP and mesitylene carboxylic acid]. 621 86


<< Previous 1 2 3 4 5 6 7 8 9 10