Enzyme inactivation by metal-catalyzed oxidation of coenzyme Q1.
Ubiquinol-1 in aerated aqueous solution inactivates several enzymes--alanine aminotransferase, alkaline phosphatase, Na+/K(+)-ATPase, creatine kinase and glutamine synthetase--but not isocitrate dehydrogenase and malate dehydrogenase. Ubiquinone-1 and/or H2O2 do not affect the activity of alkaline phosphatase and glutamine synthetase chosen as model enzymes. Dioxygen and transition metal ions, even if in trace amounts, are essential for the enzyme inactivation, which indeed does not occur under argon atmosphere or in the presence of metal chelators. Supplementation with redox-active metal ions (Fe3+ or Cu2+), moreover, potentiates alkaline phosphatase inactivation. Since catalase and peroxidase protect while superoxide dismutase does not, hydrogen peroxide rather than superoxide anion seems to be involved in the inactivation mechanism through which oxygen active species (hydroxyl radical or any other equivalent species) are produced via a modified Haber-Weiss cycle, triggered by metal-catalyzed oxidation of ubiquinol-1. The lack of efficiency of radical scavengers and the almost complete protection afforded by enzyme substrates and metal cofactors indicate a 'site-specific' radical attack as responsible for the oxidative damage.
Istituto di Chimica Biologica, Università Cattolica del S. Cuore, Facoltà di Medicina e Chirurgia, Agostino Gemelli, Roma, Italy.
A
A
Mordente
G E
GE
Martorana
E
E
Meucci
S A
SA
Santini
G P
GP
Littarru
D000410:Alanine Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002384:Catalysis; D002412:Cations; D002417:Cattle; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008670:Metals / Q000494:pharmacology*; D010084:Oxidation-Reduction; D004369:Pentetic Acid / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013379:Substrate Specificity; D013552:Swine; D014451:Ubiquinone / Q000378:metabolism*
D002412:Cations; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D008670:Metals; D014451:Ubiquinone; D004369:Pentetic Acid; D000410:Alanine Transaminase; D003402:Creatine Kinase; D000469:Alkaline Phosphatase; D005974:Glutamate-Ammonia Ligase; D000254:Sodium-Potassium-Exchanging ATPase; C025203:Ubiquinone Q1