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Argininosuccinic acid synthetase deficiency in a hamster cell line and its complementation of argininosuccinic aciduria human fibroblasts
Author(s) -
GonzálezNoriega A.,
Verduzco J.,
Prieto E.,
Velázquez A.
Publication year - 1980
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf02312521
Subject(s) - citrulline , arginine , complementation , argininosuccinate lyase , hela , chinese hamster , cell culture , biochemistry , argininosuccinate synthase , canavanine , biology , urea cycle , microbiology and biotechnology , chemistry , cell , amino acid , genetics , gene , phenotype
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.