Purine and Pyrimidine Metabolism in Man VIII pp 363-366 | Cite as
Adenylosuccinate Lyase Deficiency: An Update
Abstract
Adenylosuccinate lyase (adenylosuccinase, ASase) catalyzes both the conversion of succinylaminoimidazole carboxamide (SAICAR) into AICAR in the de novo pathway of purine synthesis, and that of adenylosuccinate (S-AMP) into AMP in the conversion of IMP into AMP. The deficiency of ASase, the first enzyme deficiency reported in man on the purine biosynthetic pathway, was discovered in 1984 (1). The hallmark of the defect is the accumulation in body fluids, particularly cerebrospinal fluid and urine, of two normally undetectable compounds, SAICAriboside and succinyladenosine (S-Ado). These succinyl-purines are the products of the dephosphorylation of the two substrates of ASase by cytosolic 5’-nucleotidase(s) (2).
Keywords
Adenine Nucleotide Purine Nucleotide Nucleoside Triphosphate Purine Synthesis Total IncorporationPreview
Unable to display preview. Download preview PDF.
References
- 1.Jaeken J, Van den Berghe G. An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet 2: 1058–56, 1984.PubMedGoogle Scholar
- 2.Van den Berghe G, Jaeken J. Adenylosuccinase deficiency. Adv Exp Med Biol 195A: 27–33, 1986.CrossRefGoogle Scholar
- 3.Jaeken J, Wadman SK, Duran M, van Sprang FJ, Beemer FA, Holl RA, Theunissen PM, de Cock P, van den Bergh F, Vincent MF, van den Berghe G. Adenylosuccinase deficiency: an inborn error of purine nucleotide synthesis. EurJ Pediatr 148: 126–31, 1988.CrossRefGoogle Scholar
- 4.Laikind PK, Seegmiller JE, Gruber HE. Detection of 5’-phosphoribosyl-(N-succinyl-carboxamide)-5-aminoimidazole in urine by use of the Bratton-Marshall reaction: identification of patients deficient in adenylosuccinate lyase activity. Anal Biochem 156: 81–90, 1986.PubMedCrossRefGoogle Scholar
- 5.Stone RL, Aimi J, Barshop BA, Jaeken J, Van den Berghe G, Zalkin H, Dixon JE. A mutation in adenylosuccinate lyase associated with mental retardation and autistic features. Nature Genetics 1: 59–63, 1992.PubMedCrossRefGoogle Scholar
- 6.Van den Bergh F, Vincent MF, Jaeken J, Van den Berghe G. Residual adenylosuccinase activities in fibroblasts of adenylosuccinase-deficient children: parallel deficiency with adenylosuccinate and succinyl-AICAR in profoundly retarded patients and non-parallel deficiency in a mildly retarded girl. J Inker Metab Dis 16: 415–24, 1993.CrossRefGoogle Scholar
- 7.Van den Bergh F, Vincent MF, Jaeken J, Van den Berghe G. Radiochemical assay of adenylosuccinase. Demonstration of parallel loss of activity toward both adenylosuccinate and succinylamidazole carboxamide ribotide in liver of patients with the enzyme defect. Analyt Biochem 193: 287–91, 1991.PubMedCrossRefGoogle Scholar
- 8.Van den Bergh F, Vincent MF, Jaeken J, Van den Berghe G. Functional studies in fibroblasts of adenylosuccinase-deficient children. J Inker Metab Dis 16: 425–34, 1993.CrossRefGoogle Scholar
- 9.Giles NH, Partridge CWH, Nelson JH. The genetic control of adenylosuccinase in Neurosopora Crassa. Proc Natl Acad Sci USA 43: 826–34, 1957.CrossRefGoogle Scholar
- 10.Gollub EG, Gots JS. Purine metabolism in bacteria. VI. Accumulations by mutants lacking adenylosuccinase. J Bacteriol 78: 320–25, 1959.PubMedGoogle Scholar
- 11.Patterson D. Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism. IV. Isolation of a mutant which accumulates adenylosuccinic acid and succinylaminoimidazole carboxamide ribotide. Somat Cell Genet 2: 189–203, 1976.PubMedCrossRefGoogle Scholar
- 12.Laikind PK, Gruber HE, Jansen I, Miller L, Hoffer M, Seegmiller JE, Willis RC, Jaeken J, Van den Berghe G. Purine biosynthesis in Chinese hamster cell mutants and human fibroblasts partially deficient in adenylosuccinate lyase. Adv Exp Med Biol 195B: 363–69, 1986.CrossRefGoogle Scholar