Restoration of nitrogen homeostasis in a man with ornithine transcarbamylase deficiency.
We evaluated the hypothesis that sodium phenylbutyrate-induced phenylacetylglutamine biosynthesis in a man with partial ornithine transcarbamylase (OTC) deficiency has a dual effect; it provides an additional vehicle for waste nitrogen excretion, and in the process it suppresses the patient's residual urea N synthesis, which then may be available for N homeostasis if the need arises. A 38-year-old man was studied over three periods. Period I was a control period during which he received a fixed caloric and N intake plus L-citrulline. Phenylbutyrate was added in period II and was maintained during period III, during which his N intake was increased. Plasma levels of ammonium and glutamine and net urea N synthesis were measured in each period; phenylacetylglutamine N synthesis was measured in periods II and III. These studies demonstrated that phenylbutyrate administration led to a 73% decrease in net de novo urea N synthesis during period II, which subsequently increased threefold in period III in response to the increased N intake. Phenylacetylglutamine N synthesis was 2.27 g/d, similar to his estimated maximum net urea N synthesis of 2.65 g/d. During periods II and III, his plasma levels of ammonium and glutamine improved as compared with period I when they were abnormally high. We conclude that sodium phenylbutyrate treatment of patients with urea cycle disorders who have significant residual enzyme activity results in both an improvement in waste N excretion and improved N homeostasis as a result of the generation of a reserve urea N synthetic capacity. This therapeutic approach may be useful in other nitrogen accumulation decreases, eg, portal-systemic encephalopathy.
Brusilow
S W
SW
Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD 21205.
Finkelstien
J
J
D000328:Adult; D001120:Arginine / Q000378:metabolism; D005973:Glutamine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008297:Male; D009584:Nitrogen / Q000502:physiology*; D009954:Ornithine Carbamoyltransferase / Q000502:physiology; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D010654:Phenylbutyrates / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000097:blood; D014508:Urea / Q000378:metabolism
D010654:Phenylbutyrates; D000644:Quaternary Ammonium Compounds; D005973:Glutamine; D014508:Urea; C003089:phenylacetylglutamine; D001120:Arginine; D009954:Ornithine Carbamoyltransferase; D009584:Nitrogen