Inactivation of lipoamide dehydrogenase by cobalt(II) and iron(II) Fenton systems: effect of metal chelators, thiol compounds and adenine nucleotides.
Fe(II)- and Co(II)-Fenton systems (FS) inactivated the lipoamide reductase activity but not the diaphorase activity of pig-heart lipoamide dehydrogenase (LADH). The Co(II) system was the more effective as LADH inhibitor. Phosphate ions enhanced the Fe(II)-FS activity. EDTA, DETAPAC, DL-histidine, DL-cysteine, glutathione, DL-dithiothreitol, DL-lipoamide, DL-thioctic acid, bathophenthroline, trypanothione and ATP, but not ADP or AMP, prevented LADH inactivation. Reduced disulfide compounds were more effective protectors than the parent compounds. Mg ions counteracted ATP protective action. Glutathione and DL-dithiothreitol partially restored the lipoamide dehydrogenase activity of the Fe(II)-FS-inhibited LADH. DL-histidine exerted a similar action on the Co(II)-FS-inhibited enzyme. Ethanol, mannitol and benzoate did not prevent LADH inactivation by the assayed Fenton systems and, accordingly, it is postulated that site-specific generated HO. radicals were responsible for LADH inactivation. With the Co(II)-FS, oxygen reactive species other than HO., might contribute to LADH inactivation.
Gutierrez Correa
J
J
Bioenergetics Research Centre, School of Medicine, University of Buenos Aires, Argentina.
Stoppani
A O
AO
D000227:Adenine Nucleotides / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D003035:Cobalt / Q000378:metabolism / Q000494:pharmacology*; D008058:Dihydrolipoamide Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism / Q000494:pharmacology; D007501:Iron / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000494:pharmacology; D013552:Swine
D000227:Adenine Nucleotides; D002614:Chelating Agents; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D017665:Hydroxyl Radical; D003035:Cobalt; D007501:Iron; D008058:Dihydrolipoamide Dehydrogenase