Inhibition of pyruvate dehydrogenase complex by moniliformin.
The mechanism for the inhibition of pyruvate dehydrogenase complex from bovine heart by moniliformin was investigated. Thiamin pyrophosphate proved to be necessary for the inhibitory action of moniliformin. The inhibition reaction was shown to be time-dependent and to follow first-order and saturation kinetics. Pyruvate protected the pyruvate dehydrogenase complex against moniliformin inactivation. Extensive dialysis of the moniliformin-inactivated complex only partially reversed inactivation. Moniliformin seems to act by inhibition of the pyruvate dehydrogenase component of the enzyme complex and not by acting on the dihydrolipoamide transacetylase or dehydrogenase components, as shown by monitoring the effect of moniliformin on each component individually. On the basis of these results, a suicide inactivator mechanism for moniliformin on pyruvate dehydrogenase is proposed.
P S
PS
Gathercole
P G
PG
Thiel
J H
JH
Hofmeyr
D003503:Cyclobutanes / Q000494:pharmacology*; D003956:Dialysis; D007700:Kinetics; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013835:Thiamine Pyrophosphate / Q000494:pharmacology
D003503:Cyclobutanes; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; C008539:moniliformin; D019289:Pyruvic Acid; D013835:Thiamine Pyrophosphate