Regional Renal Adenosine Triphosphate Metabolism in Thiamine Deficiency

Abstract

This study assesses the effect of progressive thiamine deficiency and its subsequent repletion on renal adenosine triphosphate (ATP) metabolism and the activity of pyruvate decarboxylase and transketolase. Since renal cortex is primarily dependent on fatty acid metabolism whereas renal medulla utilizes glucose, these areas were studied separately. The data show a substantial fall in both pyruvate decarboxylase and transketolase activity during thiamine deficiency, with cortex and medulla equally affected. The medullary ATP concentration fell progressively and significantly with increasing thiamine deficiency, while cortical ATP remained normal. With thiamine administration there was a rapid return to normal of medullary ATP which correlated much better with a rise in pyruvate decarboxylase than transketolase activity. Thiamine pyrophosphate in vitro also fully reversed the depressed pyruvate decarboxylase of thiamine-deficient kidney but had no effect on transketolase activity. Data were obtained which suggest that regional renal metabolic rate is not increased in thiamine deficiency. This study therefore documents a rapidly reversible fall in medullary ATP concentration with thiamine deficiency and suggests that this effect is related to depressed pyruvate decarboxylation and presumably decreased ATP synthesis via the TCA cycle. Consistent with this concept the renal cortex which subserves primarily on nonglucose substrates shows no decrease in ATP.