INHIBITORY EFFECT OF THIOPENTONE ON THE PYRUVIC DEHYDROGENASE IN BRAIN: REVERSIBILITY OF ACTION BY THIAMINE PYROPHOSPHATE AND LIPOIC ACID

Abstract

A study of the effect of Thiopentone sodium on pyruvate oxidation in brain tissue revealed that the action of this drug could be attributed primarily to an inhibition of pyruvic dehydrogenase, the enzyme which degrades pyruvate to the level of acetate. Of the four cofactors needed by the enzyme, thiamine pyrophosphate (TPP) and lipoic acid (Lp) modified the inhibition when added separately. The inhibition was completely relieved when thiamine pyrophosphate and lipoic acid were added together, suggesting that Thiopentone may be competing not with either alone but with a complex of the two such as "lipothiamide pyrophosphate". Alpha-Ketoglutaric dehydrogenase, which requires the same cofactors as pyruvic dehydrogenase, was somewhat less affected by Thiopentone sodium.