Argininosuccinic aciduria
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The diagnostic metabolic characteristic is argininosuccinic aciduria. Hyperammonemia may be massive in the neonatal form. In patients with variant forms of the disease, it is usually episodic and less dramatically elevated. Plasma concentrations of glutamine and alanine are mostly elevated while plasma citrulline is slightly increased as is urinary orotic acid. Plasma arginine may be low. Argininosuccinic acid is specific and best found in the urine. This compound is so efficiently excreted that it may be missed in the blood, as it can also overlie the peak for leucine or isoleucine.. High levels are found in the cerebrospinal fluid. In the urine, argininosuccinic acid is excreted in gram quantities. Values for argininosuccinic acid and its anhydride in the urine ranged from 1163 to 6060 mmol/mol creatinine [19]. However, it may sometimes be missed on routine assays even of the urine for amino acids because the compound is unstable, the peaks occur in a place unfamiliar to the operator, or they may overlap those of other amino acids. The best way to assay for argininosuccinic acid is to boil the urine; this quantitatively converts the compound to its anhydrides, which are then readily seen on the amino acid analyzer [27].
Amino acid disorders and urea cycle disorders
Steve Hannigan in Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
This disorder is one of a group of conditions, known as the urea cycle disorders, in which the body’s ability to manage dietary protein is impaired. In argininosuccinic aciduria there is a deficiency or absence of the enzyme argininosuccinate lyase (ASL), which is an important part of the urea cycle. This leads to an accumulation of the amino acid argininosuccinic acid (hence the name), and may lead to a build-up of ammonia (and its related product glutamine) in the body, giving rise to the symptoms of the disorder.
Diseases of the Nervous System
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
The major feature of citrullinuria is the presence of large amounts of citrullin in body fluids. In this condition, the plasma level is higher than that in the cerebrospinal fluid. Argininosuccinic acid synthetase activity is defective and, consequently, great amounts of citrullin are excreted in the urine. The production and elimination of citrullin is related to dietary protein intake.
Metabolomics markers in Neurology: current knowledge and future perspectives for therapeutic targeting
Published in Expert Review of Neurotherapeutics, 2020
Roberta Bonomo, Guido Cavaletti, Debra J. Skene
Considering the growing evidence of impaired circadian rhythms in Huntington’s disease (HD) animal models, Morton and colleagues investigated alterations in melatonin and cortisol levels in pre-symptomatic transgenic HD sheep [165]. The authors found normal concentrations of serotonin and cortisol, whereas levels of plasma melatonin were significantly elevated, thus suggesting a compensatory neuroprotective response of melatonin in the first stages of the disorder. A number of studies have reported raised levels of citrulline in both pre-clinical and clinical models of HD, suggesting a dysfunction in the urea and NO cycles [166–168]. The possible dysregulation of CCAAT-enhancer-binding proteins (C/EBP) due to mutant huntingtin has been proposed as a causative mechanism of argininosuccinic acid synthetase and argininosuccinase acid lyase suppression [166].
Metabolomics reveals the effects of hydroxysafflor yellow A on neurogenesis and axon regeneration after experimental traumatic brain injury
Published in Pharmaceutical Biology, 2023
En Hu, Teng Li, Zhilin Li, Hong Su, Qiuju Yan, Lei Wang, Haigang Li, Wei Zhang, Tao Tang, Yang Wang
In the cortex, the HSYA-responsive metabolites were primarily enriched in ‘Arginine biosynthesis,’ ‘Arginine and proline metabolism,’ ‘Phenylalanine, tyrosine and tryptophan biosynthesis’ pathways. The related metabolites were proline, d-proline, l-phenylalanine, ornithine, l-(+)-citrulline and argininosuccinic acid. While in the hippocampus, the differential pathway was the ‘phenylalanine, tyrosine, and tryptophan biosynthesis’ pathway where l-phenylalanine hit (Figure 3(K), Table 2).
Inherited hyperammonemias: a Contemporary view on pathogenesis and diagnosis
Published in Expert Opinion on Orphan Drugs, 2018
Evelina Maines, Giovanni Piccoli, Antonia Pascarella, Francesca Colucci, Alberto B. Burlina
Increased level of Cit may be suggestive for ASSD, ASLD and citrin-D. In ASLD, argininosuccinic acid (ASA) will also be present. An increased Arg is suggestive for ARG1D [82], while a low Cit concentration can be detected in patients with CPS1D, NAGSD and OTCD.
Related Knowledge Centers
- Argininosuccinate Lyase
- Argininosuccinate Synthase
- Aspartic Acid
- Citrulline
- Fumaric Acid
- Urea Cycle
- Amino Acid
- Citric Acid Cycle
- Arginine
- NON-Proteinogenic Amino Acids