Tetraphenylphosphonium inhibits oxidation of physiological substrates in heart mitochondria.
We show that tetraphenylphosphonium inhibits oxidation of palmitoylcarnitine, pyruvate, malate, 2-oxoglutarate and glutamate in heart mitochondria in the range of concentration (1-5 microM) commonly used for the determination of mitochondrial membrane potential. The inhibition of 2-oxoglutarate (but not other substrate) oxidation by tetraphenylphosphonium is dependent on the concentration of 2-oxoglutarate and on extramitochondrial free calcium, and the kinetic plots are consistent with a mixed type of inhibition. Our results indicate that tetraphenylphosphonium interacts with enzymes, specifically involved in the oxidation of 2-oxoglutarate, most possibly, 2-oxoglutarate dehydrogenase.
Mildaziene
V
V
Institute for Biomedical Research, Kaunas Medical Academy, Lithuania.
Baniene
R
R
Marcinkeviciute
A
A
Nauciene
Z
Z
Kalvenas
A
A
Zimkus
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004579:Electron Transport; D008564:Membrane Potentials / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats
D009861:Onium Compounds; D009943:Organophosphorus Compounds; D002118:Calcium; C013289:tetraphenylphosphonium