Argininosuccinate synthetase is an enzyme that participates in the urea cycle, which is a sequence of chemical reactions that takes place in the cells of the liver. The urea cycle processes excess nitrogen (which is generated as the body uses proteins) into a compound called urea that is excreted from the body in urine.
Argininosuccinate synthase is responsible for the third step of the urea cycle. This reaction combines two amino acids (building blocks of proteins), citrulline and aspartate, to form a molecule called argininosuccinic acid. A series of additional chemical reactions uses argininosuccinic acid to form urea.
The gene that encodes for this enzyme, ASS is located on chromosome 9q34.
Citrullinemia: At least 50 mutations that cause type I citrullinemia have been identified in the ASS gene. Most of these mutations substitute one amino acid for another amino acid in the argininosuccinate synthetase enzyme. These mutations likely affect the structure of the enzyme and its ability to bind to citrulline, aspartate, and other molecules. A few mutations lead to the production of an abnormally short enzyme that cannot effectively play its role in the urea cycle.
Defects in argininosuccinate synthase disrupt the third step of the urea cycle, preventing the liver from processing excess nitrogen into urea. As a result, nitrogen (in the form of ammonia) and other byproducts of the urea cycle (such as citrulline) build up in the bloodstream. Ammonia is toxic, particularly to the nervous system. An accumulation of ammonia during the first few days of life leads to poor feeding, vomiting, seizures, and the other signs and symptoms of type I citrullinemia.
Multilocus linkage analysis with the human argininosuccinate synthetase gene
Northrup H, Lathrop M, Lu SY, Daiger SP, Beaudet AL, O'Brien WE Genomics 1989 Oct;5(3):442-444 Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
We have identified three restriction fragment length polymorphisms (RFLPs) from within the argininosuccinate synthetase (ASS) gene which maps to human chromosome 9q34-qter. Although RFLPs at pseudogene loci are detected by the cDNA, these are the first polymorphisms reported at the ASS locus. The three RFLPs are in linkage equilibrium with each other, and haplotypes for the ASS locus are highly informative. Two-locus recombination estimates between ASS and seven other 9q markers indicated that ASS is closest to the [ABO blood group]? with a recombination fraction of 0.04 (0.005-0.11). A multilocus lod score analysis with these seven 9q markers indicated that ASS maps between ABL and MCT136 close to ABO, but it is uncertain if ASS is centromeric or telomeric to ABO.