Argininosuccinic acid synthetase deficiency in a hamster cell line and its complementation of argininosuccinic aciduria human fibroblasts.
Unlike normal human cells, cultured fibroblasts from patients with argininosuccinic aciduria cannot synthesize arginine from citrulline because they have a deficiency of argininosuccinic acid lyase (ASL). We have found that V79, a Chinese hamster cell line, cannot grow on citrulline. Although these cells show a normal uptake of citrulline and have levels of ASL comparable to a human cell line (HeLa) which can grow in citrulline-containing medium, V79 cells have less than 5% of the argininosuccinic acid synthetase (ASS) activity of HeLa and cannot convert citrulline to argininosuccinate and thence to arginine. When heterokaryocytes are formed between V79 and a human cell line derived from a patient with ASL deficiency, complementation takes place and citrulline is incorporated into cell protein, presumably after having been converted to arginine. This is the first time that a genetic defect of the urea cycle has been corrected in human cells.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives*; D001123:Argininosuccinate Lyase / Q000235:genetics / Q000378:metabolism*; D001124:Argininosuccinate Synthase / Q000172:deficiency* / Q000235:genetics; D001125:Argininosuccinic Acid / Q000652:urine*; D002460:Cell Line; D002956:Citrulline / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005808:Genes, Recessive; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells; D008025:Ligases / Q000172:deficiency*; D008099:Liver / Q000201:enzymology; D008190:Lyases / Q000378:metabolism*; D008297:Male; D000608:Renal Aminoacidurias / Q000378:metabolism*
D001125:Argininosuccinic Acid; D002956:Citrulline; D001120:Arginine; D008190:Lyases; D001123:Argininosuccinate Lyase; D008025:Ligases; D001124:Argininosuccinate Synthase