Different extent of inhibition of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase both containing endogenous thiamine pyrophosphate, by some anticoenzyme analogues.
Inhibitory effects of 4'-oxythiamine pyrophosphate (OTPP) and tetrahydrothiamine pyrophosphate (ThTPP) on the purified bison heart pyruvate dehydrogenase complex (PDC) semisaturated with endogenous thiamine pyrophosphate (TPP) and 2-oxoglutarate dehydrogenase complex (OGDC) saturated about 85% with endogenous TPP, were studied. It has been established that the thiamine derivatives strongly inhibit not only the PDC apoenzyme moiety, but also the PDC holoenzyme moiety. The apparent I50 values for the holoenzyme were 0.006 microM and 0.046 microM for OTPP and ThTPP, respectively. The inhibition of the PDC is reversible. After removal of the anticoenzyme analogues by gel filtration the endogenous TPP within the PDC is retained as it is evidenced by complete recovery of the enzyme activity without added TPP. In contrast with the PDC, OGDC holoenzyme form is weakly inhibited by the anticoenzyme analogues.
Strumilo
S
S
Department of Biochemistry, University of Warsaw, Branch in Bialystok, Poland.
Czygier
M
M
Markiewicz
J
J
D000818:Animals; D016164:Bison; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007655:Ketoglutarate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D007700:Kinetics; D015394:Molecular Structure; D009206:Myocardium / Q000201:enzymology; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D013835:Thiamine Pyrophosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011768:Pyruvate Dehydrogenase Complex; C037342:tetrahydrothiamine pyrophosphate; D007655:Ketoglutarate Dehydrogenase Complex; D013835:Thiamine Pyrophosphate