Quinaldate as an inhibitor of mitochondrial oxidation at the substrate dehydrogenase level

Quinaldate (quinoline-2-carboxylate) inhibits the oxidation of substrates of rat-liver and kidney mitochondria. The concentration of quinaldate required to cause a 50-per-cent inhibition of ADP-activated oxygen uptake slightly differs with various substrates in the same type of mitochondria, and differs with the same substrate in the case of the two types of mitochondria and lies within the mM order of magnitude. In higher concentrations, quinaldate also inhibits the resting respiration (i.e. without ADP). The endogenous respiration of liver mitochondria is also inhibited. The inhibition of oxygen uptake of uncoupled or repeatedly frozen and thawed mitochondria shows the same sensitivity to quinaldate as that of untreated mitochondria in the presence of ADP. TMPD +ascorbate oxidation is not inhibited at all. NADH oxidation (in sonicated mitochondria) is only slightly inhibited even by high concentrations of quinaldate. The inhibition by quinaldate is reversible and of mixed type with respect to 3-hydroxybutyrate as substrate in liver mitochondria, with a Ki of about 0.1 mM. It can be concluded that quinaldate inhibits mitochondrial oxidation at the level of substrate dehydrogenases.