Short-term effects of sodium arsenite (AsIII) and sodium arsenate (AsV) on carbohydrate metabolism in the perfused rat liver

The actions of arsenite and arsenate on carbohydrate metabolism in the once-through perfused rat liver were investigated. The compound inhibited lactate gluconeogenesis with an IC50 of 25 mu M. It also increased glycolysis and fructolysis at concentrations between 10 and 100 mu M. This effect was paralleled by strong inhibition of pyruvate carboxylation (IC50 = 4.25 mu M) and by a relatively moderate diminution in the ATP levels. The inhibitory action of arsenate on pyruvate carboxylation and lactate gluconeogenesis was 103 times less effective than that of arsenite. For realistic doses and concentrations (<< 1 mM), impairment of metabolism by arsenate can be expected to occur solely after its reduction to arsenite. Arsenite, on the other hand, can be regarded as a strong short-term modifier of lactate gluconeogenesis and other pathways. The main cause of the former is inhibition of pyruvate carboxylation, a hitherto unknown effect of arsenic compounds.