China
Africa
Explore chapters and articles related to this topic
The Sparse-Fur (Otcspf) and Abnormal Skin and Hair (Otcash) Mutations, Chromosome X
Published in John P. Sundberg, Handbook of Mouse Mutations with Skin and Hair Abnormalities, 2020
John P. Sundberg, Donald P. Doolittle
Ornithine transcarbamylase is a mitochondrial enzyme in the urea cycle that catalyzes the formation of citrulline from carbamoyl phosphate and ornithine.6 Mutant forms of this enzyme have been described in sparse-fur and in abnormal skin and hair mice.2,7 The enzymatic abnormality can be detected in the liver, duodenum, jejunum, and ileum.8 Mouse ornithine transcarbamylase is a trimer, similar to that in other species. The sparse-fur mutation does not affect the molecular weight of this enzyme. The affinity for ornithine and norvaline is decreased in mutant mice.9 Livers of hemizygous abnormal skin and hair mice synthesize two distinct ornithine transcarbamylase precursor polypeptides; one is normal in size, and the second is elongated. Both enzymes are processed by mitochondria, but only the one of normal size is assembled into the active trimer.10 The molecular lesion is a C to A transversion of the ornithine transcarbamylase gene in the sparse-fur mouse mutation that alters a histidine residue to an asparagine residue at amino acid 117.11 Correction of this enzymatic deficiency has been successful using transgenic approaches.12–16
Citrullinemia type I
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The molecular defect in citrullinemia is in the enzyme, argininosuccinic acid synthetase. This is a cytosolic enzyme in contrast to ornithine transcarbamylase and carbamylphosphate synthetase (Chapters 26 and 27). Argininosuccinic acid synthetase catalyzes the conversion of citrulline and aspartic acid to argininosuccinic acid (see Figure 28.1). The enzyme is widely distributed in tissues. The defect has usually been demonstrated in cultured fibroblasts [8, 9], and it has also been demonstrated in the liver [1, 4, 19]. Neonatal-onset cases have less than five percent of normal activity in liver, whereas late-onset cases have 10 to 25 percent of normal activity [29].
Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
In hyperammonemia, the only established biochemical defect is the elevated blood ammonia level. This even may be associated with the deficiency of ornithine transcarbamylase or carbamyl phosphate synthetase. These enzymes are located in the liver and both types of disorders have been demonstrated. Consumption of a low-protein-containing diet reduces blood ammonia.
High levels of blood glutamic acid and ornithine in children with intellectual disability
Published in International Journal of Developmental Disabilities, 2022
Muhammad Wasim, Haq Nawaz Khan, Hina Ayesha, Abdul Tawab, Fazal e Habib, Muhammad Rafique Asi, Mazhar Iqbal, Fazli Rabbi Awan
In the current screening analysis, it was found that 40 intellectually disabled patients had high levels of glutamic acid and ornithine as compared to healthy children. Ornithine and glutamic acid have a role in different disorders and also develop autistic features in children. Urea Cycle Disorders (UCD) occur universally with variable frequencies in different populations, while Ornithine Transcarbamylase (OTC) deficiency has been reported to be the most commonly occurring UCD (Bijarnia-Mahay et al.2018). Similarly, in the current study, the level of ornithine was high in 40 patient samples, which may be the cases of urea cycle defects and Pyrroline-5-carboxylate synthase deficiency (Perez-Arellano et al.2010), reflecting that might be this disorder is common in Pakistan; however, further confirmation is required by advanced analytical techniques.
Metabolomic markers predictive of hepatic adaptation to therapeutic dosing of acetaminophen
Published in Clinical Toxicology, 2022
Brandon J. Sonn, Kennon J. Heard, Susan M. Heard, Angelo D’Alessandro, Kate M. Reynolds, Richard C. Dart, Barry H. Rumack, Andrew A. Monte
Ornithine concentrations, a metabolite involved with the urea cycle, in pre APAP administration samples was predictive of subjects that would need to undergo hepatic adaptation while taking the drug. Since it has been shown that APAP will increase ornithine levels [28], it makes sense that elevated ornithine prior to APAP administration would be associated with subsequent ALT elevation. Allantoate, also involved in urea production, was identified as being significantly elevated in pre APAP administration samples for subjects who would undergo hepatic adaptation. When adjusting for time series, citrulline concentration decreases were also significant, which further highlights the urea cycle relevance to the transient ALT elevation and subsequent adaptation. Increased levels of 5-l-glutamyl-l-glutamine have been observed to be associated with hyperammonemia and urea cycle dysfunction [29]. While there have been prior investigations into the predictive nature of urea as a marker of APAP-associated hepatic injury, they have not led to significant results [30,31]. Therefore, the significant involvement of the urea cycle is likely related to mitochondrial dysfunction, hepatocyte death, and the hepatic adaptation pathway. This may represent variable expression of ornithine transcarbamylase, therefore, we will follow up with analyses that examine genetic variants in this enzyme.
Hyperammonemia in the setting of Roux-en-Y gastric bypass presenting with osmotic demyelination syndrome
Published in Journal of Community Hospital Internal Medicine Perspectives, 2021
Carly Rosenberg, Michael Rhodes
With the increasing rate of obesity in the USA, bariatric surgery continues to be offered as a weight loss treatment. However, over time, there have been multiple case reports on the correlation between RYGB and hyperammonemia in the absence of cirrhosis or liver disease [1–4]. The onset of hyperammonemic encephalopathy after RYGB has been shown to present at various intervals, ranging from months to years [1]. In this case, the patient had a RYGB approximately 20 years prior to presentation. RYGB hyperammonemia has been observed more so in women, and in some cases, women with X-linked heterozygous ornithine transcarbamylase deficiency who had previously been asymptomatic [1]. Multiple nutritional deficiencies have been associated with this syndrome as well including hypoalbuminemia, multiple amino acid deficiencies, hypoglycemia and low zinc levels, many of which were seen in this patient [2]. Nutritional deficiencies are thought to play a role in the urea cycle, interfering with the elimination of ammonia. In addition, RYGB alters the anatomy of the gastrointestinal system, which can cause intestinal overgrowth, leading to the production of ammonia from urease-producing bacteria (Figure 2) [1,2].