Pyruvate inhibition of pyruvate dehydrogenase kinase is a physiological variable.

Pyruvate inhibited pyruvate dehydrogenase kinase activity in mitochondria from adipose tissue, heart, brain and kidney of fed rats. Starvation for 24 h led to increased kinase activity in mitochondria from adipose tissue and heart but not from brain or kidney and to reduction of pyruvate inhibition of the enzyme from adipose tissue, heart and brain. Insulin injection into starved animals rapidly restored pyruvate inhibition without alteration of kinase activity in adipose tissue and heart mitochondria. Induction of streptozotocin diabetes resulted in loss of pyruvate inhibition of the kinase in heart mitochondria at 48 h but not at 24 h whereas a significant increase of kinase activity was seen at 24 h. It is concluded that the mechanisms which control fluctuations of pyruvate sensitivity of the kinase are different from the mechanisms which control fluctuations of the uninhibited kinase activity.