Effect of oxythiamine on adrenal thiamine pyrophosphate-dependent enzyme activities.

The effect of parenterally administered low doses of oxythiamine (0.5 mumol/100 g body weight every 12 h) on rat adrenal transketolase, pyruvate dehydrogenase ( PDC ) and 2-oxoglutarate dehydrogenase complex ( OGDC ) activities was studied. It was found that the transketolase and the PDC activities decreased after 12, 16, and 20 injections. When the activities were measured in the absence of exogenous thiamine pyrophosphate (TPP), the PDC inhibition was significant after 20 oxythiamine injections. The OGDC activity was resistant to oxythiamine administration. The oxythiamine effects seem to be due to its being phosphorylated to yield diphosphate ester which, as kinetic studies on highly purified PDC from bovine adrenals have shown, is a strong competitive inhibitor (Ki = 0.07 microM) with respect to TPP (Km = 0.11 microM). The data obtained provide evidence for the possibility of a partial selective in vivo inhibition of the adrenal TPP-dependent enzymes.