Abstract
Residual adenylosuccinate lyase activity was studied in cultured lymphoblasts from a pair of siblings who have mental retardation and autism, and who have been previously shown to exhibit a deficiency of the enzyme. Utilization of formate by intact cells showed de novo synthesis in the mutant lymphoblasts to be similar to normal, consistent with a partial deficiency of this enzyme as previously reported. The steady-state kinetics and thermal stability of adenylosuccinate lyase were examined in the lymphoblast lysates. The pH-activity curves were nearly identical for the mutant and normal cells, with an optimum in the region of pH 7.8. While the substrate affinity was not distinguishable from normal, there was a significant difference (p < 0.05) In the Vmax of the mutant cells. The lyase from normal cells exhibited an apparent Km of 3.3 ± 0.8 μM and a Vmax of 13.8 ± 0.9 nmol·mg−1·min−1. In the mutant cells, the lyase had an apparent Km of 2.6 ± 0.5 μM and Vmax of 6.7 ± 1.1 nmol mg−1·min−1. There was a significant difference between the normal and mutant cell lyases with regard to thermal stability. At 37°C, the half-time for inactivation was 22.2 hours for the normal cells and 15.7 hours for the mutant cell lysates, and at 60°C the half-times were 5.0 and 0.49 minutes for normal and mutant cell lysates, respectively. There was no evidence of inhibitory activity in the lysates of the mutant cells. The results are consistent with a structural mutation in the adenylosuccinate lyase gene of the affected individuals.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Barshop, B., Alberts, A. & Gruber, H. 9 STUDIES OF MUTANT HUMAN ADENYLOSUCCINATE LYASE. Pediatr Res 24, 112 (1988). https://doi.org/10.1203/00006450-198807000-00033
Issue Date:
DOI: https://doi.org/10.1203/00006450-198807000-00033