Suppression of beta-oxidation restores pyruvate inhibition of pyruvate dehydrogenase kinase in starved rat heart.

Kinetic behaviour of rat heart pyruvate dehydrogenase kinase (PDHK alpha) was studied in the multi-enzyme complex (PDC) contained in two preparations: mitochondria (mPDC) and a high speed pellet of Triton-extracted tissue (hPDC). Two parameters were evaluated: Vav, related to Vmax, and Fractional Pyruvate Inhibition (FPI). Starvation of rats for 48 h led to a rise in Vav and a fall in FPI. Injection into starved rats of agents which reduce beta-oxidation of fatty acids restored, in succession, FPI and then Vav, of hPDC, to levels found in hPDC from fed animals. In vitro incubation at 30 degrees C of hPDC from starved animals restored FPI, but not Vav to 'fed' values; both were restored during in vitro incubation of mPDC from starved animals within the same time frame as in the in vivo experiments. A sharp increase of FPI, but not Vav, of hPDC from both fed and starved rats was observed in later experiments. This could have been due to differential selection of the two genes for isoenzymes of PDHK alpha proposed by other workers.