The ASL gene provides instructions for making the enzyme argininosuccinate lyase. This enzyme primarily participates in the urea cycle, a series of reactions that occur in liver cells. The urea cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys. Excreting the excess nitrogen prevents it from accumulating in the form of ammonia.
The specific role of the argininosuccinate lyase enzyme is to start the reaction in which the amino acid arginine, a building block of proteins, is produced from argininosuccinate, the molecule that carries the waste nitrogen collected earlier in the urea cycle. The arginine is later broken down into urea, which is excreted, and ornithine, which restarts the urea cycle.
In cells throughout the body, the argininosuccinate lyase enzyme is also involved in moving (transporting) arginine into cells to make a compound called nitric oxide. Nitric oxide is important for regulating blood flow and blood pressure.
Health Conditions Related to Genetic Changes
More than 130 mutations in the ASL gene have been found to cause argininosuccinic aciduria. In some cases, a short sequence of DNA is deleted from the gene. Other mutations replace one protein building block (amino acid) with another amino acid in the argininosuccinate lyase enzyme. In people of Arab ancestry, two common mutations replace the amino acid glutamine with a premature stop signal at position 116 (written as Gln116Ter or Q116*) or position 354 (written as Gln354Ter or Q354*) in the argininosuccinate lyase enzyme. Mutations in the ASL gene may result in an argininosuccinate lyase enzyme that is unstable, misshapen, or quickly broken down.
If the argininosuccinate lyase enzyme is misshapen or missing, it cannot fulfill its role in the urea cycle. Arginine is not produced, excess nitrogen is not converted to urea for excretion, and ammonia accumulates in the body. This buildup of ammonia damages the brain and other tissues and causes neurological problems and other signs and symptoms of argininosuccinic aciduria. It is unclear how a lack of arginine contributes to the features of this condition.More About This Health Condition
Other Names for This Gene
- arginosuccinate lyase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Al-Sayed M, Alahmed S, Alsmadi O, Khalil H, Rashed MS, Imtiaz F, Meyer BF. Identification of a common novel mutation in Saudi patients with argininosuccinic aciduria. J Inherit Metab Dis. 2005;28(6):877-83. doi: 10.1007/s10545-005-0081-2. Citation on PubMed
- Biochemistry (fifth edition, 2002): Ammonium Ion is Converted into Urea in Most Terrestrial Vertebrates.
- Christodoulou J, Craig HJ, Walker DC, Weaving LS, Pearson CE, McInnes RR. Deletion hotspot in the argininosuccinate lyase gene: association with topoisomerase II and DNA polymerase alpha sites. Hum Mutat. 2006 Nov;27(11):1065-71. doi: 10.1002/humu.20352. Citation on PubMed
- Erez A, Nagamani SC, Shchelochkov OA, Premkumar MH, Campeau PM, Chen Y, Garg HK, Li L, Mian A, Bertin TK, Black JO, Zeng H, Tang Y, Reddy AK, Summar M, O'Brien WE, Harrison DG, Mitch WE, Marini JC, Aschner JL, Bryan NS, Lee B. Requirement of argininosuccinate lyase for systemic nitric oxide production. Nat Med. 2011 Nov 13;17(12):1619-26. doi: 10.1038/nm.2544. Citation on PubMed or Free article on PubMed Central
- Linnebank M, Tschiedel E, Haberle J, Linnebank A, Willenbring H, Kleijer WJ, Koch HG. Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene. Hum Genet. 2002 Oct;111(4-5):350-9. doi: 10.1007/s00439-002-0793-4. Epub 2002 Aug 14. Citation on PubMed
- Nagamani SCS, Erez A, Lee B. Argininosuccinate Lyase Deficiency. 2011 Feb 3 [updated 2019 Mar 28]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK51784/ Citation on PubMed
- Reid Sutton V, Pan Y, Davis EC, Craigen WJ. A mouse model of argininosuccinic aciduria: biochemical characterization. Mol Genet Metab. 2003 Jan;78(1):11-6. doi: 10.1016/s1096-7192(02)00206-8. Citation on PubMed
- Tanaka T, Nagao M, Mori T, Tsutsumi H. A novel stop codon mutation (X465Y) in the argininosuccinate lyase gene in a patient with argininosuccinic aciduria. Tohoku J Exp Med. 2002 Oct;198(2):119-24. doi: 10.1620/tjem.198.119. Citation on PubMed
- Turner MA, Simpson A, McInnes RR, Howell PL. Human argininosuccinate lyase: a structural basis for intragenic complementation. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9063-8. doi: 10.1073/pnas.94.17.9063. Citation on PubMed or Free article on PubMed Central
- Yu B, Howell PL. Intragenic complementation and the structure and function of argininosuccinate lyase. Cell Mol Life Sci. 2000 Oct;57(11):1637-51. doi: 10.1007/pl00000646. Citation on PubMed
- Yu B, Thompson GD, Yip P, Howell PL, Davidson AR. Mechanisms for intragenic complementation at the human argininosuccinate lyase locus. Biochemistry. 2001 Dec 25;40(51):15581-90. doi: 10.1021/bi011526e. Citation on PubMed
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