title: Studies on the mechanism for renal elimination of N-acetylphenylalanine: its pathophysiologic significance in phenylketonuria.
abstract: To elucidate the mechanism and biologic significance of urinary occurrence of N-acetylphenylalanine in phenylketonuria, the metabolic fate of N-acetylphenylalanine was studied in rats. In vivo and in vitro analysis revealed that N-acetyl-14C(ul)-phenylalanine bound to plasma albumin with an association constant of 8.52 X 10(3) M-1 and that the number of binding sites was 0.98 per mole albumin. Intravenously administered N-acetylphenylalanine was rapidly extracted from the circulation predominantly by the kidney and excreted into urine. Plasma clearance of the injected ligand was markedly decreased by bilateral nephrectomy but not by bilateral ureter ligation. Probenecid, a potent inhibitor of the renal excretory system for organic anions, such as hippuric acid, sharply decreased the rate of disappearance from the circulation, renal accumulation, and urinary secretion of intravenously administered N-acetylphenylalanine. These results indicate that intravenously administered N-acetylphenylalanine undergoes renal peritubular transport via a probenecid-sensitive excretory system for organic anions. This renal transtubular excretory mechanism may possibly operate in elimination of N-acetylphenylalanine, a hazardous amphipathic metabolite of phenylalanine, from plasma into urine in phenylketonuric patients.
mesh_terms: D000818:Animals; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008026:Ligation; D008297:Male; D009392:Nephrectomy; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D010661:Phenylketonurias / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism; D014513:Ureter / Q000502:physiology
chemical_list: D012709:Serum Albumin; D010649:Phenylalanine; C044228:N-acetylphenylalanine; D011339:Probenecid