The effect of phosphorylation on pyruvate dehydrogenase.
Phosphorylation of the pyruvate dehydrogenase component (E1) of the muscle pyruvate dehydrogenase complex (PDC) by E1-kinase inhibits substrate conversion both in oxidative and non-oxidative reactions. Circular dichroism spectra were used to monitor the effect of phosphorylation on the following stages of the process: holoform formation from apo-E1 and thiamine pyrophosphate (TPP), substrate binding and active site deacetylation. It has been shown that phosphorylation of E1 reduces its affinity for TPP and prevents holo-E1 interaction with pyruvate. Phosphorylated and dephosphorylated PDC convert 2-hydroxyethyl-TPP in similar ways involving half of their active sites; all active sites of E1 function in the presence of deacetylating agents. The data obtained suggest that the phosphorylation and substrate binding sites interact with each other.
Korotchkina
L G
LG
A. N. Bakh Institute of Biochemistry, Russian Academy of Sciences, Moscow.
Khailova
L S
LS
Severin
S E
SE
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002942:Circular Dichroism; D010856:Columbidae; D066298:In Vitro Techniques; D007700:Kinetics; D009132:Muscles / Q000201:enzymology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex / Q000737:chemistry* / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013379:Substrate Specificity; D013835:Thiamine Pyrophosphate / Q000378:metabolism
D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D013835:Thiamine Pyrophosphate