Abstract
Adenylosuccinate lyase (ASMP lyase, EC4.3.2.2) is the terminal enzyme j in de novo adenylate synthesis and as such acts to convert adenylosuccinate (AS) monophosphate to adenosine monophosphate. This enzyme also participates in the de novo synthesis of IMP converting 5′-phosphoribosyl-4-(N-succino carboxamide)-5-aminoimidazole (SAICAR) to 5′-phosphoribosyl-5-amino-4-imidazolecarboxamide (AICAR). Recently Jaeken, et al. described three patients with neurologic dysfunctions including infantile autism syndrome (1) who had elevated levels of AS and a compound tentatively identified as SAICA riboside in urine, blood, and cerebral spinal fluid. These patients have a markedly decreased but varying activity of ASMP lyase in various tissues studied. Deficiency of ASMP lyase has previously been described in mutagenized and nutrient-selected Chinese Hamster Ovary fibroblasts (CHO-Ade I cells) (2,3). These cells excrete excess ASMP and SAICAR into the culture medium. In the present study of purine nucleotide metabolism of CHO-Ade I cells and fibroblasts from a AS and SAICA riboside over-producing patient we examined the effect of ASMP lyase deficiency on branchpoint enzyme activities and on de novo synthesis by comparison to the control cell lines, wild type parent cells (CHO-K1) and fibroblasts from age-matched normal individuals, respectively.