China 
Africa 
Explore chapters and articles related to this topic
Inborn Errors of Metabolism
Published in Praveen S. Goday, Cassandra L. S. Walia, Pediatric Nutrition for Dietitians, 2022
Surekha Pendyal, Areeg Hassan El-Gharbawy
The purpose of the urea cycle is to convert the ammonia arising from ingested protein and endogenous protein turnover to urea in the liver. Six different enzymes and two transport proteins are required for the completion of the urea cycle (Figure 23.4). Deficiency in any of the six enzymes can result in the buildup of ammonia to toxic levels causing neurologic damage. Deficiencies in transport proteins, citrin, and ornithine translocase cause metabolic disorders that are clinically different from the classic UCD. Except for OTC deficiency, all enzyme defects in the urea cycle are inherited in an autosomal-recessive manner. OTC deficiency is inherited as an X-linked dominant trait and is usually lethal in males. Hyperammonemia is a common biochemical feature of all UCDs with the proximal enzyme defects (e.g., Carbamoylphosphate synthetase I [CPS I], argininosuccinate synthetase [ASS]) generally having a more severe presentation than distal defects (e.g., argininosuccinic acid lyase [ASL], arginase [ARG]).
Alternative Tumor-Targeting Strategies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
ADI, which is produced by a bacterium, degrades arginine which is crucial to the metabolism and growth of certain tumor cells, whereas normal human cells can synthesize it from metabolic precursors via the urea cycle. One of the steps in this pathway involves the argininosuccinate synthase (ASS)-catalyzed conversion of citrulline to argininosuccinate. Some tumor cell types, such as melanoma, mesothelioma, hepatocellular carcinoma, and pancreatic and prostate cancers, are deficient in ASS and must instead obtain arginine from the blood for survival and growth. Therefore, depleting arginine from the bloodstream and tissues can control tumor growth and potentially destroy arginine-requiring cancers without damaging healthy cells.
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
Citrullinemia was first reported in 1962 [1] in a patient with impaired mental development. Soon after, it became apparent that the classic presentation is as a typical neonatal hyperammonemia that was, until the development of modern methods of pharmacologic therapy, uniformly lethal [2–8]. The picture is indistinguishable from that of the male neonate with ornithine transcarbamylase deficiency (Chapter 26). The activity of argininosuccinate synthetase (EC 6.3.4.5) is widely expressed in tissues (Figure 28.1). Its deficiency is readily demonstrated in cultured fibroblasts [9]. The gene (CTNL1) has been cloned [10] and mapped to chromosome 9 at q34.11 [11]. About 100 mutations have been described [12–15].
Deficiency of PSRC1 accelerates atherosclerosis by increasing TMAO production via manipulating gut microbiota and flavin monooxygenase 3
Published in Gut Microbes, 2022
Tiantian Luo, Zhigang Guo, Dan Liu, Zhongzhou Guo, Qiao Wu, Qinxian Li, Rongzhan Lin, Peier Chen, Caiwen Ou, Minsheng Chen
In addition, the effect of PSRC1 deletion on other bacterial species and metabolites likewise indicated that PSRC1 is a protective factor. For example, A. muciniphila, Mucispirillum and Adlercreutzia were markedly depleted in the gut of DKO mice. A. muciniphila, as a next-generation beneficial microbe, has reduced plasma cholesterol and inflammation levels, improved insulin sensitivity and ameliorated atherosclerotic lesion areas in animal and human studies.36Adlercreutzia inhibits hyperlipidemia and obesity,37 while Mucispirillum plays a role in inhibiting inflammation.38 Conversely, the enriched genus Helicobacter may become an opportunistic pathogen, which would cause pro-inflammatory cytokine production and hyperlipidemia.39 PSRC1 deletion also activates urease and its accessory protein UreE and enriches the proton-gated inner membrane channel protein UreI, all of which favor H. pylori survival in acidic environments. ArgG, a gene encoding argininosuccinate synthase, is a crucial rate-limiting enzyme involved in arginine synthesis and the uric acid cycle.40 The sequencing data showed that PSRC1 deletion downregulated ArgG levels, which may reduce the tolerance of beneficial bacteria to acid stress and thus inhibit growth performance.
Targeted metabolomics reveals differential biological effects of nanoplastics and nanoZnO in human lung cells
Published in Nanotoxicology, 2019
Swee Ling Lim, Cheng Teng Ng, Li Zou, Yonghai Lu, Jiaqing Chen, Boon Huat Bay, Han-Ming Shen, Choon Nam Ong
Moreover, in arginine and proline metabolism pathway, arginine is synthesized from citrulline by the continuous action of cytosolic enzymes (argininosuccinate synthetase/argininosuccinate lyase). Under the action of arginases, arginine is converted into urea and ornithine. Ornithine is transported into the mitochondria through the mitochondrial inner membrane and participates in the synthesis of citrulline to complete the ornithine cycle (Tapiero et al. 2002). Increased arginine levels (Figure 5(C)) in our study was supported by nanoTiO2 study, which demonstrated similar trend in arginine accompanying with decreased urea and ornithine (Tucci et al. 2013). Lower activity of urea and ornithine cycle led to reduce polyamine synthesis, which then might signify reduced proliferation. Thus, this could partly explain the cytotoxic effect of nanoPS.
Arginine-lowering enzymes against cancer: a technocommercial analysis through patent landscape
Published in Expert Opinion on Therapeutic Patents, 2018
Rakhi Dhankhar, Pooja Gulati, Sanjay Kumar, Rajeev Kumar Kapoor
L-asparaginase, which destroys the free source of aspargine, was approved by the Food and Drug Administration for the treatment of T-cell acute lymphoblastic lymphoma [5]. This success has drawn the attention of many research groups toward arginine. Arginine is a nonessential amino acid (essential for neonates) which is involved in various cellular functions like synthesis of nitric oxide, polyamines, nucleotides, proline, glutamate, and proteins [6]. In normal cells, arginine is synthesized in the urea cycle, enzyme argininosuccinate synthetase (ASS) catalyzes the reaction forming argininosuccinate from L-citrulline, and the enzyme argininosuccinate lyase (ASL) finally converts argininosuccinate into L-arginine (Figure 1) [1]. Several tumors including hepatocellular carcinoma (HCC), malignant melanoma, malignant pleural mesothelioma (MPM), and prostate and renal cancer are arginine auxotrophic, due to variable loss or downregulation of ASS [7]. These cancerous cells rely upon exogenous arginine for survival and will die of starvation in presence of arginine-degrading enzymes.