Lemmi 1990 Biochem Med Metab Biol
| Lemmi CA, Pelikan PC, Geesaman B, Seamon E, Koyle M, Rajfer J (1990) Kinetics of cyclosporine A-induced inhibition of succinate-coenzyme Q dehydrogenase in rat renal cortical mitochondria. Biochem Med Metab Biol 43:214-25. https://doi.org/10.1016/0885-4505(90)90027-x |
Lemmi CA, Miller RL, Rajfer J (1990) Biochem Med Metab Biol
Abstract: The kinetic mechanism of succinate-coenzyme Q dehydrogenase (Complex II) inhibition by cyclosporine A (CS) on rat renal cortical mitochondria was investigated. CS showed two modes of inhibition of Complex II of the mitochondrial electron transport system: (a) a mixed linear noncompetitive inhibition of resting succinate-limited and ADP-stimulated respirations suggesting that CS binds to Complex II at a different site than the substrate, affecting the dissociation constant for the enzyme-substrate complex and (b) a competitive inhibition of the DNP-stimulated electron transport system suggesting competition with the oxidized form of a component of Complex II. CS action to renal mitochondrial Complex II limits its function, an effect which may be related to CS nephrotoxicity.
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Selected quotes
- Since mitochondrial Complex II also participates in the oxidation of fatty acids (6), we designed a group of experiments to determine whether CS also inhibits fatty acid-supported mitochondrial respiration.
- In the oxidation of fatty acids, Complex II interacts with an electron transfer flavoprotein which transfers electrons between reduced flavin and coenzyme Q (6, [Gustafson 1986 J Biol Chem |lO]).
- Oxygen solubility in buffer of 390 ng atoms O/ml at 37°C.
- Rotenone, an inhibitor of Complex I, and acetoacetate, to divert NADH to the formation of p-hydroxybutyrate, were used to assure that only electrons from the flavoprotein-linked oxidation were coupled to the measured mitochondrial respiration. Malate was added to obtain a more physiological situation (8).
Labels:
Enzyme: Complex II;succinate dehydrogenase
