title: Catecholamines enhance dihydrolipoamide dehydrogenase inactivation by the copper Fenton system. Enzyme protection by copper chelators.
abstract: Catecholamines (CAs: epinephrine, norepinephrine, dopamine, L-DOPA, 6-hydroxydopamine) and o-diphenols (DOPAC and catechol) enhanced dihydrolipoamide dehydrogenase (LADH) inactivation by Cu(II)/H2O2 (Cu-Fenton system). The inhibition of LADH activity correlated with Cu(II), H2O2 and CA concentrations. Similar inhibitions were obtained with the assayed CAs and o-diphenols. CAs enhanced HO. radical production by Cu(II)/H2O2, as demonstrated by benzoate hydroxylation and deoxyribose oxidation; LADH counteracted the pro-oxidant effect of CAs by scavenging hydroxyl radicals. Captopril, dihydrolipoamide, dihydrolipoic acid, DL-dithiothreitol, GSSG, trypanothione and histidine effectively preserved LADH from oxidative damage, whereas N-acetylcysteine, N-(2-mercaptopropionylglycine) and lipoamide were less effective protectors. Catalase (though neither bovine serum albumin nor superoxide dismutase) protected LADH against the Cu(II)/H2O2/CAs systems. Denatured catalase protected less than the native enzyme, its action possibly depending on Cu-binding. LADH increased and Captopril inhibited epinephrine oxidation by Cu(II)/H2O2 and Cu(II). The summarized evidence supports the following steps for LADH inactivation: (1) reduction of LADH linked-Cu(II) to Cu(I) by CAs; (2) production of HO. from H2O2 by LADH-linked Cu(I) (Haber-Weiss reaction) and (3) oxidation of aminoacid residues at the enzyme active site by site-specifically generated HO. radicals. Hydrogen peroxide formation from CAs autoxidation may contribute to LADH inactivation.
authors.affiliation: Bioenergetics Research Centre, School of Medicine (University of Buenos Aires), Paraguay, Argentina.
authors.forename: J G
authors.initials: JG
authors.lastname: Correa
authors.forename: A O
authors.initials: AO
authors.lastname: Stoppani
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002216:Captopril / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology; D008058:Dihydrolipoamide Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017665:Hydroxyl Radical; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D008322:Mammals; D009638:Norepinephrine / Q000494:pharmacology; D010084:Oxidation-Reduction; D016627:Oxidopamine / Q000494:pharmacology; D010396:Penicillamine / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D002396:Catechols; D002614:Chelating Agents; C045076:Fenton's reagent; D015102:3,4-Dihydroxyphenylacetic Acid; D017665:Hydroxyl Radical; D003300:Copper; D016627:Oxidopamine; D002216:Captopril; D006861:Hydrogen Peroxide; D007501:Iron; D008058:Dihydrolipoamide Dehydrogenase; D010396:Penicillamine; D003545:Cysteine; C034221:catechol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine