alpha-Ketoglutarate regulation of glutamine transport and deamidation in renal mitochondria

Abstract

alpha-Ketoglutarate (KG) is a potent inhibitor of renal mitochondrial glutamine transport and deamidation at physiological concentrations. The concentration-inhibition relationship observed between KG and mitochondrial glutamine transport and deamidation indicates that changes in renal KG concentration occurring during alterations in acid-base balance would have significant effects on mitochondrial ammonia production in vivo. A rapid-mixing, rapid-filtration method was developed to measure the effects of KG on initial rates of mitochondrial glutamine transport. Transport was linear for only a few seconds and approached steady-state conditions by 30 seconds. KG (0.3 mM) raised the glutamine transport Km approximately two-fold. We propose that KG may play a major regulatory role in the early adaptation of renal ammonia production to acidosis.