Regulation of pea mitochondrial pyruvate dehydrogenase complex activity: inhibition of ATP-dependent inactivation.
In contrast to the pyruvate dehydrogenase complex (PDC) from animal mitochondria, our in situ and in vitro studies indicate that the ATP:ADP ratio has little or no effect in regulating the mitochondrial pyruvate dehydrogenase complex from green pea seedlings. Pyruvate was a competitive inhibitor of ATP-dependent inactivation (Ki = 59 microM), while the PDC had a Km for pyruvate of microM. Thiamine pyrophosphate, the coenzyme for the pyruvate dehydrogenase (PDH) component of the complex, did not inhibit ATP-dependent inactivation when used alone but it enhanced inhibition by pyruvate. As such, thiamine pyrophosphate was a competitive inhibitor (Ki = 130 nM) of ATP-dependent inactivation. A model is proposed for the pyruvate plus thiamine pyrophosphate inhibition of ATP-dependent inactivation of the pyruvate dehydrogenase complex in which pyruvate exerts its inhibition of inactivation by altering or protecting the protein substrate from phosphorylation and not by directly inhibiting PDH kinase.
Budde
R J
RJ
Department of Biochemistry, University of Missouri, Columbia 65211.
Randall
D D
DD
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D007887:Fabaceae; D006706:Homeostasis; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D010944:Plants / Q000201:enzymology*; D010946:Plants, Medicinal; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*
D011768:Pyruvate Dehydrogenase Complex; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate