Catecholamines Enhance Dihydrolipoamide Dehydrogenase Inactivation by the Copper Fenton System. Enzyme Protection by Copper Chelators
作者:
CorreaJ. Gutierrez,
StoppaniA. O. M.,
期刊:
Free Radical Research
(Taylor Available online 1996)
卷期:
Volume 24,
issue 4
页码: 311-322
ISSN:1071-5762
年代: 1996
DOI:10.3109/10715769609088028
出版商: Taylor&Francis
关键词: lipoamide dehydrogenase;copper;hydrogen per oxide;hydroxyl radicals;oxidative damage;catecholamines;thiol compounds;copper chelators;Captopril
数据来源: Taylor
摘要:
Catecholamines (CAs: epinephrine, norepinephrine, dopamine, L-DOPA, 6-hydroxydopamine) ando-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), H2O2and CA concentrations. Similar inhibitions were obtained wit! 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, dihydrolipo amide, dihydrolipoic acid, DL-dithiothreitol, GSSG, try-panothione 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. Dena tured catalase protected less than the native enzyme, its action possibly depending on Cu-binding. LADH in creased and Captopril inhibited epinephrine oxidation by Cu(II)/H2O2and 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 H2O2by 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.
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