Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cimetidine has been demonstrated to impair microsomal oxidative drug metabolizing and other enzyme systems in mouse liver. The inhibition is rapid, occurring after a single administration and also found to be dose-dependent. It is more significant after daily administration for 15 days. Enzyme inhibition by ranitidine, another H2-receptor antagonist was comparatively less at all the concentrations of the drug tested. An increased activity of alkaline phosphatase, glutamate-pyruvate and glutamate-oxaloacetate transaminase was observed in liver with cimetidine administration, whereas that of lactate and succinate dehydrogenase was inhibited only after administration of 2000 mg cimetidine per kg body weight. Except alkaline phosphatase other enzymes were unaffected after ranitidine administration. Analysis of lipid classes in liver showed that phospholipid, triglycerides and free fatty acid contents were significantly decreased in drug administration while cholesterol level showed very little or no change. Microsomal and soluble protein contents were significantly increased which probably indicate that the inhibition in the enzyme activity by histamine H2-receptor antagonists may be a lipid mediated process and not resulted from the reduced availability of the enzyme protein.
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PMID:Interaction of H2-receptor antagonists, cimetidine and ranitidine with microsomal drug metabolizing and other systems in liver. 179 70

Carboxamide fungicides target succinate dehydrogenase (SDH). Recent field monitoring studies have identified Botrytis cinerea isolates resistant to one or several SDH inhibitors (SDHIs) with amino acid substitutions in the SDH B subunit. We confirmed, by site-directed mutagenesis of the sdhB gene, that each of the mutations identified in field strains conferred resistance to boscalid in B.cinerea, and in some cases cross-resistance to other SDHIs (fluopyram, carboxin). Enzyme inhibition studies showed that the studied modifications (SdhB_P225T/L/F, N230I, H272Y/R/L) affected the inhibition of SDH activity by SDHIs, directly contributing to resistance. Our results confirm the importance of H272, P225 and N230 for carboxamide binding. Modifications of P225 and N230 conferred resistance to the four carboxamides tested (boscalid, fluopyram, carboxin, bixafen). Modifications of H272 had differential effects on the susceptibility of SDH to SDHIs. SdhB(H272L) , affected susceptibility to all SDHIs, SdhB(H272R) conferred resistance to all SDHIs tested except fluopyram, and SdhB(H272Y) conferred fluopyram hypersensitivity. Affinity-binding studies with radiolabelled fluopyram revealed strong correlations among the affinity of SDHIs for SDH, SDH inhibition and in vivo growth inhibition in the wild type. The sdhB(H272Y) mutation did not affect SDH and respiration activities, whereas all the other mutations affected respiration by decreasing SDH activity.
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PMID:Site-directed mutagenesis of the P225, N230 and H272 residues of succinate dehydrogenase subunit B from Botrytis cinerea highlights different roles in enzyme activity and inhibitor binding. 2411 86