Different Extent of Inhibition of Pyruvate Dehydrogenase and 2-Oxoglutarate Dehydrogenase Both Containing Endogenous Thiamine Pyrophosphate, by Some Anticoenzyme Analogues

Abstract

Inhibitory effects of 4′-oxythiamine pyrophosphate (OTPP) and tetrahydrothiaminc 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 lj., values for the holoenzyme were 0.006 μM and 0.046 μM 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.

Key Words: :

• Pyruvate dehydrogenase
• 2-oxoglutarate dehydrogenase
• inhibition
• thiamine pyrophosphate analogues