Regulation of pyruvate dehydrogenase in mitochondria of rat liver.

Abstract

Active (dephospho) and inactive (phospho) forms of pyruvate dehydrogenase are extracted from freshly prepared rat liver mitochondria in the same proportion as from freeze‐clamped samples of whole rat liver. The active form increases within a few minutes on incubation of mitochondria with pyruvate (state 4) in a concentration‐dependent manner, the maximal effect (80% active form) being obtained at 2 mM pyruvate. Half‐maximal activation occurs between 0.3 and 0.4 mM pyruvate. ADP, in the absence of exogenous substrate, also stimulates the formation of active pyruvate dehydrogenase. Palmitoyl‐l(–)‐carnitine counteracts the effects of pyruvate or ADP on pyruvate dehydrogenase interconversion. The lowest values of the active form of the enzyme were observed during state 4 respiration with palmitoyl‐l(–)‐carnitine, succinate, 2‐oxoglutarate, and 3‐hydroxybutyrate. These studies lend support to the view that, in liver, the state of the pyruvate dehydrogenase system is under metabolic control and that ADP may thereby play an essential role.