Detection of kinetically abnormal argininosuccinate synthase in neonatal citrullinemia by conversion of citrulline to arginine in intact fibroblasts.
The apparent Km values of argininosuccinate synthase toward citrulline and aspartate were significantly increased in cultured skin fibroblasts from one patient with neonatal citrullinemia, whereas, those determined in cells from three other patients were within the normal range. The abnormal apparent Km of the mutant enzyme toward aspartate was determined by a ureagenesis assay system (0.14 mmol/l as compared with 0.010-0.018 mmol/l for the normal enzyme), and the abnormal values toward citrulline were measured by both arginine synthesis (6.1 mmol/l as compared with 0.21-0.26 mmol/l for the normal enzyme) and ureagenesis (0.63 as compared with 0.043-0.067) assay systems.
Ben-Yoseph
Y
Y
Department of Pediatrics, C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201.
Mitchell
D A
DA
D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology*; D001120:Arginine / Q000096:biosynthesis*; D001124:Argininosuccinate Synthase / Q000378:metabolism*; D002478:Cells, Cultured; D002675:Child, Preschool; D002956:Citrulline / Q000097:blood / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007700:Kinetics; D008025:Ligases / Q000378:metabolism*; D009154:Mutation; D012867:Skin / Q000166:cytology
D002956:Citrulline; D001120:Arginine; D008025:Ligases; D001124:Argininosuccinate Synthase