Amino acid disorders and urea cycle disorders
Steve Hannigan in Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
The urea cycle disorders (UCDs) are a group of genetic disorders that are caused by a deficiency of one of six enzymes in the urea cycle, which is responsible for the removal of ammonia. These six enzymes are: arginaseargininosuccinate lyaseargininosuccinate synthetasecarbamyl phosphate synthetaseN-acetylglutamate synthetaseornithine transcarbamylase.
Inborn Errors of Metabolism
Praveen S. Goday, Cassandra L. S. Walia in Pediatric Nutrition for Dietitians, 2022
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
David E. Thurston, Ilona Pysz in 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.
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.
Intestinal luminal putrescine is produced by collective biosynthetic pathways of the commensal microbiome
Published in Gut Microbes, 2019
Atsuo Nakamura, Takushi Ooga, Mitsuharu Matsumoto
Notably, arginine (M + 9 and + 7), citrulline (M + 7), ornithine (M + 5, + 6, and + 7), and putrescine (M + 5) were detected in rats, even though these metabolites are not produced by the forward linear pathways of arginine deiminase, ornithine decarboxylase, or arginine decarboxylase. This result suggests that arginine (M + 9 and + 7) was produced from citrulline (M + 9 and + 7) via the reverse pathway; for example, by argininosuccinate synthetase and argininosuccinate lyase. The data also indicate that citrulline (M + 7) was produced from ornithine (M + 7) by ornithine carbamoyltransferase, a bidirectional enzyme, suggesting that reverse metabolic pathways are also driven by exchange of metabolites between species. In contrast, putrescine (M + 5) may be produced from ornithine (M + 5 or + 6), which may, in turn, be produced by replacement of labelled amino groups with non-labelled amino groups via enzymes such as ornithine aminotransferase. This phenomenon provides insight into the level of complexity in collective biosynthetic pathways at the community level.
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.
Related Knowledge Centers
- Argininosuccinic Acid
- Aspartic Acid
- Chromosome 9
- Citrulline
- Enzyme
- Intron
- Urea Cycle
- Liver
- Kidney
- Adenosine Triphosphate