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)

In rats treated with single, sublethal doses of p,p'-DDT oxidative phosphorylation efficiency, respiratory activity and "latent" ATPase activity in liver and brain mitochondria were determined. A time- and dose-dependent decrease in oxidative phosphorylation efficiency was found. Time-dependent suppression of respiratory activity in state 3 was noticed and a stimulation of mitochondrial ATPase activity 24 h after DDT treatment in liver and brain mitochondria was found. The correlation between time-dependent changes in the brain mitochondrial fraction and distribution of DDT in brain after a single, oral dose is discussed. It is suggested that changes in mitochondria were caused by DDT and its metabolites. It is concluded that the uncoupling of oxidative phosphorylation especially in brain mitochondria could be responsible for some DDT intoxication symptoms in mammals.
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PMID:The mode of action of p,p'=DDT on mammalian mitochondria. 13 71

Gossypol occurs naturally in the pigment glands in cotton. It has a role in protecting cotton plants from insect pests such as bollworms, yet it was not toxic to the cotton leafworm larvae Spodoptera littoralis up to 2-5% concentration in artificial diet or at 125 micrograms/ larva by topical application. The compound inhibited protease and lipid peroxidase activities in larvae with in vitro I50 values of 1.5 X 10(-3)M, and 4.4 X 10(-4)M respectively. When gossypol was fed to Spodoptera larvae, it stimulated the microsomal N-demethylase in vitro. This inductive effect was time-dependent similar to that of phenobarbital. Gossypol stimulates ATPase at lower concentrations and inhibited it at higher concentrations. The I50 for mitochondrial ATPase was 1.7 X 10(-4)M, while the corresponding values for DDT and fenvalerate were 1.1 X 10(-4)M and 7.0 X 10(-4)M respectively. Gossypol at 1.5% concentration in the diet reduced the larval weight to 50% of the control within two days, and increased the duration of each larval stage. The number of eggs and their hatchability was seriously decreased in larvae treated for three consecutive generations. Such an effect can be attributed to the ability of gossypol to interfere with protein bio-synthesis.
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PMID:Gossypol as an inducer or inhibitor in Spodoptera littoralis larvae. 645 17

1,1-bis-(p-Chlorophenyl)-2,2,2-trichloroethane (DDT) inhibited the ATP hydrolytic activity of the ATP synthase from a DDT-susceptible insect (Apis mellifera) as well as a DDT-tolerant insect (Spodoptera littoralis), and from rat liver and bovine heart in a parallel way to its insecticidal properties and selectivity of action. Inhibition of the ATPase activity of these preparations by DDT was parallel to the poisoning of the source organism with DDT. Furthermore, both the inhibition and poisoning of insects were affected similarly by temperature. Inhibition of the insect enzyme activity by DDT was specific and differed from that by oligomycin or N,N-dicyclohexylcarbodi-imide (DCCD). PAGE analysis of the various preparations of the enzyme showed that the inhibition of the enzyme activity by DDT was associated with the presence of a selective protein band with an apparent molecular mass of 23 kDa. This protein band exists in the preparations from the DDT-susceptible insects but was absent from the preparations of the enzyme from the DDT-insensitive sources. Removal of this protein band from the enzyme rendered its activity insensitive to inhibition by DDT. The protein was purified directly from mitochondria and the DDT sensitivity was reconstituted upon its addition to the DDT-insensitive F1-ATPase. We conclude that this identified protein of the ATP synthase is the DDT target protein in insects.
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PMID:Resolving the DDT target protein in insects as a subunit of the ATP synthase. 1183 25

1,1-bis (p-chlorophenyl)-2, 2, 2-trichloroethane (DDT) has been used for control of malaria mosquitoes and other insect vectors of human diseases since 1945. Its use poses an environmental dilemma and efforts to replace it have been hampered by lack of information about its molecular target. This work identifies the 23 kDa band responsible for the DDT sensitivity in bees, as the OSCP and subunit "d" of the ATP synthase. The OSCP of the bee's ATP synthase contained 207 amino acids compared to 190 in bovine, which is insensitive to DDT, and the identities were only 47%. Subunit "d" of the bees had no counterpart in the bovine. Whether DDT is interacting only with OSCP, only with subunit "d", or with both subunits, remains to be assessed. Identification of the molecular target of DDT will lead the way to new target based insecticides aimed to protect plant, combat malaria and other insect transmitted diseases.
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PMID:The insecticide DDT targets the OSCP and subunit D of the Apis mellifera ATP synthase. 2184 89