Inhibition of bovine liver lysine-ketoglutarate reductase by urea cycle metabolites and saccharopine.
Lysine-ketoglutarate reductase was purified 675-fold from bovine liver mitochondria. Product inhibition studies gave results similar to those reported for this enzyme extracted from other sources. Inhibition studies with L-citrulline exhibited mixed inhibition patterns. No inhibition of the partially-purified enzyme by ammonium salts was detected; in contrast, marked inhibition of the enzyme by ammonium was apparently observed in crude liver homogenates. This was probably due to depletion of NADPH and/or 2-oxoglutarate in the assay mixture as a result of conversion of ammonium to glutamate by glutamate dehydrogenase. A similar explanation could account for the high levels of lysine observed in humans with urea cycle disorders.
D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002956:Citrulline / Q000494:pharmacology*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000201:enzymology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D051381:Rats; D012443:Saccharopine Dehydrogenases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D013045:Species Specificity
D002956:Citrulline; D000641:Ammonia; D000587:Oxidoreductases Acting on CH-NH Group Donors; D012443:Saccharopine Dehydrogenases; D008239:Lysine; C100169:saccharopine