ammonia is a toxic material for mammalians. it is detoxificated and converted to urea in the urea cycle in liver. each defect in the urea cycle cause increase in blood ammonia level. ornithine transcarbamylase enzyme (otc) is the second enzyme in the urea cycle that exists in mitochondria. otc deficiency is the most common hereditary disorder in the urea cycle. in this study, 45 hyper ammonia p...

The conversion of ammonia into urea by the human liver requires the coordinated function of the 6 enzymes and 2 transporters of the urea cycle. The initial and rate-limiting enzyme of the urea cycle, carbamylphosphate synthetase 1 (CPS1), requires an allosteric activator, N-acetylglutamate (NAG). The formation of this unique cofactor from glutamate and acetyl Coenzyme-A is catalyzed by N-acetyl...

N-Carbamylglutamate Accelerates Ureagenesis in Patients with Hyperammonemia N Ah Mew, E Daikhin, R McCarter, I Payan, I Nissim, M Yudkoff, M Tuchman Children's Research Institute, Children's National Medical Center, Washington, DC, Children's Hospital of Philadelphia, Philadelphia, PA The urea cycle is responsible for nitrogen regulation and balance in humans. Disruption of normal urea cycle fu...

INTRODUCTION Ornithine transcarbamylase deficiency is the most common inherited disorder of the urea cycle, has a variable phenotype, and is caused by mutations in the OTC gene. We report three cases of ornithine transcarbamylase deficiency to illustrate the late-onset presentation of this disorder and provide strategies for diagnosis and treatment. The patients were maternal first cousins, pre...

Hyperammonemic encephalopathy (he) is a rare complication of malignancy and chemotherapy. Although the cause of he is unclear, a functional arginine deficiency secondary to increased catabolism has been suggested as a possible mechanism. Either that deficiency or an undetermined metabolite could lead to inhibition of N-acetylglutamate synthase (nags), a urea cycle enzyme, resulting in hyperammo...

Arginase deficiency is caused by deficiency of arginase 1 (ARG1), a urea cycle enzyme that converts arginine to ornithine. Clinical features of arginase deficiency include elevated plasma arginine levels, spastic diplegia, intellectual disability, seizures and growth deficiency. Unlike other urea cycle disorders, recurrent hyperammonemia is typically less severe in this disorder. Normalization ...

Ornithine transcarbamoylase deficiency is the most common inherited urea cycle disorder. In adults, its phenotypes are diverse. In asymptomatic patients with late presentations, symptom onset is often associated with a precipitating factor. We present a case of a woman with urea cycle disorder diagnosed after an acute peptic ulcer bleed and fasting.

The urea cycle is the main pathway for the disposal of excess nitrogen. Carbamoylphosphate synthetase 1 (CPS1), the first and rate-limiting enzyme of urea cycle, is activated by N-acetylglutamate (NAG), and thus N-acetylglutamate synthase (NAGS) is an essential part of the urea cycle. Although NAGS deficiency is the rarest urea cycle disorder, it is the only one that can be specifically and eff...

Huntington's disease (HD) is a neurodegenerative disorder caused by the huntingtin (HTT) gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT) exists in the liver and causes urea cycle deficiency. A low protein diet (17%) restores urea cycle activity and ameliorates symp...