Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously we reported that ATPase activity was recovered when the subunit alpha + beta + gamma or alpha + beta + delta of the F1-ATPase from the thermophilic bacterium PS3 were combined under appropriate conditions. Unlike that of holoenzyme (TF1) and the alpha + beta + gamma mixture, ATPase activity of the alpha + beta + delta mixture was heat labile and insensitive to azide inhibition (Yoshida, M., Sone, N., Hirata, H., and Kagawa, Y. (1977) J. Biol. Chem. 252, 3480-3485). Here, the properties of purified subunit complexes were compared in detail with those of native TF1. The subunit stoichiometries of the complexes were determined to be alpha 3 beta 3 gamma 1 and alpha 3 beta 3 delta 1. In general, the properties of the alpha 3 beta 3 gamma complex are very similar to those of TF1, whereas those of the alpha 3 beta 3 delta complex are significantly different. ATPase activity of the alpha 3 beta 3 delta complex is cold labile. The alpha 3 beta 3 delta complex showed a less stringent specificity for substrate and divalent cation than TF1 and the alpha 3 beta 3 gamma complex. Two Km values for ATP were exhibited by the alpha 3 beta 3 delta complex with the lower one being in the range of 0.1 microM. Equilibrium dialysis experiments revealed that the alpha 3 beta 3 delta complex cannot specifically bind ADP in the absence of Mg2+, while TF1 and the alpha 3 beta 3 gamma complex bind about 1 and 3 mol of ADP/mol of enzyme, respectively. ADP-dependent inactivation of the alpha 3 beta 3 delta complex by dicyclohexylcarbodiimide was not observed. The alpha 3 beta 3 gamma complex was readily formed when the gamma subunit was added to the alpha 3 beta 3 delta complex, suggesting that the alpha 3 beta 3 delta complex is not a "dead-end" complex. The cause of thermolability of the alpha 3 beta 3 delta complex appears to be the low stability of the complex itself at high temperature and not due to an unusually low thermostability of the delta subunit.
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PMID:The reconstituted alpha 3 beta 3 delta complex of the thermostable F1-ATPase. 253 13

Many drugs differing widely in chemical structure uncouple mitochondrial oxidative phosphorylation in vitro. This observation has led to the hypothesis that in vivo uncoupling is the basis of their pharmacological activity. Serpasil, a parenteral preparation of reserpine, recently has been shown to uncouple oxidative phosphorylation in vervet monkey kidney mitochondria. Although the drug exhibits some properties of a "classical" uncoupler, our studies show that it has a dual effect on energy conservation. Reserpine released respiratory control in rat liver mitochondria only when dissolved in organic solvents (as in Serpasil) or when deprotonated. Reserpine also released the oligomycin-induced respiratory control in beef heart submitochondrial particles, and inhibited energized uptake of Ca2- by rat liver mitochondria. Reserpine had a dual effect on mitochondrial ATPase: It (a) enhanced ATP hydrolysis by intact liver mitochondria, and (b) inhibited ATP hydrolysis by submitochondrial particles of beef heart. On a molar basis, reserpine was less effective than carbonyl cyanide 3-chlorophenylhydrazone in all bioenergetic reactions examined. Homogenates and mitochondria isolated from brain and liver of rats stuporous from intraperitoneally injections of Serpasil exhibited no detectable abnormalities in respiratory states and responded to known uncouplers in the expected manner. There was no evidence of in vivo uncoupling of oxidative phosphorylation as a basis of the pharmacological activity of reserpine, although interference with energy transfer may be involved in toxic manifestations of the drug. The results indicate the need for caution in interpreting the action of drugs formulated in complex pharmaceutical preparations and based solely on in vitro experiments.
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PMID:Reserpine as an uncoupler of oxidative phosphorylation and the relevance to its psychoactive properties. 622 36

Regulation of mitochondrial functions in vivo by catecholamines was examined indirectly by depleting the catecholamines stores by reserpine treatments of the experimental animals. Reserpine treatment resulted in decreased respiratory activity in liver and brain mitochondria with the two NAD+-linked substrates: glutamate and pyruvate + malate with succinate ATP synthesis rate decreased in liver mitochondria only. With ascorbate + TMPD system, the ADP/O ratio and ADP phosphorylation rate decreased in brain mitochondria. For the heart mitochondria, state 3 respiration rates decreased for all substrates. In the liver mitochondria basal ATPase activity decreased by 51%, but in the presence of Mg2+ and/or DNP increased significantly. In the brain and heart mitochondria ATPase activities were unchanged. The energy of activation in high temperature range increased liver mitochondrial ATPase while in brain mitochondria reserpine treatment resulted in abolishment in phase transition. Total phospholipid (TPL) content of the brain mitochondria increased by 22%. For the heart mitochondria TPL content decreased by 19% and CHL content decreased by 34%. Tissue specific differential effects were observed for the mitochondrial phospholipid composition. Liver mitochondrial membranes were more fluidized in the reserpine-treated group. The epinephrine and norepinephrine contents in the adrenals decreased by 68 and 77% after reserpine treatment.
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PMID:Effect of catecholamine depletion on oxidative energy metabolism in rat liver, brain and heart mitochondria; use of reserpine. 1108 15