ISSN:
1573-2665
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary Adenylosuccinase (ASase) catalyses both the conversion of succinylaminoimidazole carboxamide ribotide (succinyl-AICAR) into AICAR and that of adenylosuccinate into AMP in the synthesis of purine nucleotides. Its deficiency results in the accumulation in body fluids of the nucleosides corresponding to both substrates, succinyl-AICAriboside and succinyladenosine. Two main subtypes of the defect are type I with severe mental retardation and succinyladenosine/succinyl-AICAriboside ratios around 1, and type II with slight mental delay and succinyladenosine/succinyl-AICAriboside ratios around 4. We report that in fibroblasts of type I patients, the activity of ASase with both adenylosuccinate and succinyl-AICAR is about 30% of normal. In contrast, in type II fibroblasts, the activity with adenylosuccinate is only 3% of normal, whereas that with succinyl-AICAR is also 30% of normal. If also present in other tissues, this non-parallel deficiency provides an explanation for the higher concentration of succinyladenosine in type II. In type I fibroblasts, ASase is further characterized mainly by a 3-fold to 4-fold increase inK m for succinyl-AICAR, and by retarded elution from an anion exchanger. In type II fibroblasts, ASase is characterized by a similar increase inK m for succinyl-AICAR but by a potent inhibition by KCl and nucleoside triphosphates, and by a normal elution profile. These results suggest a modification of the surface charge of ASase in type I, and the addition of one or more positively charged residues in the active site in type II.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00710291
