Disease relevance of ARGININOSUCCINIC ACID

• An infant is described who died at 6 days of age with hyperammonemia and argininosuccinic acid in the urine [1].
• We monitored a pregnancy in a family at risk for citrullinemia due to argininosuccinic acid (ASA) synthetase deficiency [2].
• Patients with argininosuccinic aciduria due to a deficiency of argininosuccinic acid lyase are uniquely prone to chronic hepatitis, potentially leading to cirrhosis [3].
• The growth rate of several polyamine-deficient mutants of Escherichia coli was very low in minimal medium and increased markedly upon the addition of putrescine, spermidine, arginine, citrulline, or argininosuccinic acid [4].

High impact information on ARGININOSUCCINIC ACID

• These data provide evidence that, if precise control is maintained over tissue culture variables, citrullinemia can be diagnosed successfully in utero by microassay of ASA synthetase activity in cultured amniotic fluid cells [2].
• The pregnancy was terminated, and the in utero diagnosis was confirmed by assay of ASA synthetase activity in cultured fetal skin fibroblasts (4.4% of control activity) [2].
• ASA was not detected in amniotic fluid from the second fetus at risk, and ASA lyase activity in cultured cells was 80% of control activity [5].
• Enzymatic analysis of erythrocyte lysate confirmed the diagnosis of an unaffected child (ASA lyase = 46% of control) and indicated heterozygosity [5].
• In addition, eight fetal tissues were analyzed for ASA, and all had significant accumulation [5].

Chemical compound and disease context of ARGININOSUCCINIC ACID

• Metabolic studies of these mice demonstrated that they have the same biochemical phenotype as humans, with hyperammonemia, elevated plasma argininosuccinic acid and low plasma arginine [6].
• Hyperammonemia, elevation of glutamic acid and argininosuccinic acid and its anhydrides confirmed the diagnosis of ALD [7].

Anatomical context of ARGININOSUCCINIC ACID

• ASA was easily measured in amniotic fluid from the first fetus at risk, whereas none was detectable in control fluids [5].
• Amniotic fluid cells cultured from this fetus had only 5.5% of control ASA lyase activity [5].
• All patients showed elevated concentrations of argininosuccinic acid and its anhydrides in all body fluids, most pronounced in cerebrospinal fluid (CSF) [8].

Associations of ARGININOSUCCINIC ACID with other chemical compounds

• The enzyme-catalyzed formation of argininosuccinic acid from citrulline and aspartate by recombinant human and rat liver argininosuccinate synthetase was inhibited by fumonisin B1 [9].
• Nevertheless, the brain showed extensive microscopic changes and a marked accumulation of argininosuccinic acid, varying between regions from 1.8 to 4.4 mmol/l. Brain contents of glutamine, glutamic acid, and alpha-amino-n-butyric acid were also greatly elevated, with a lesser elevation of citrulline, and a normal arginine content [10].
• Argininosuccinic aciduria (ASA-uria) is a rare inborn error of the urea cycle, in which there is massive excretion of argininosuccinic acid (ASA) in the urine together with elevated concentrations of ASA in the plasma and the CSF [11].

Analytical, diagnostic and therapeutic context of ARGININOSUCCINIC ACID

• Expression, purification, crystallization and preliminary X-ray analysis of human argininosuccinic acid lyase [12].
• Rapid, specific HPLC method for the determination of argininosuccinic acid following pre-column derivatization with o-phthaladehyde [13].

References