alpha-Ketoglutarate regulation of glutamine transport and deamidation in renal mitochondria.
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.
D000136:Acid-Base Equilibrium; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D007656:Ketoglutaric Acids; D005973:Glutamine; D005972:Glutaminase