Argininosuccinic acid synthetase deficiency in a hamster cell line and its complementation of argininosuccinic aciduria human fibroblasts.

Abstract

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.

• Authors: A González-Noriega, J Verduzco, E Prieto, A Velázquez
• Journal: Journal of inherited metabolic disease (J Inherit Metab Dis) Vol. 3 Issue 2 Pg. 45-8 ( 1980) ISSN: 0141-8955 [Print] United States
• PMID: 6777600 (Publication Type: Journal Article)

Chemical References

• Argininosuccinic Acid
• Citrulline
• Arginine
• Lyases
• Argininosuccinate Lyase
• Ligases
• Argininosuccinate Synthase

Topics

• Animals
• Arginine (analogs & derivatives)
• Argininosuccinate Lyase (genetics, metabolism)
• Argininosuccinate Synthase (deficiency, genetics)
• Argininosuccinic Acid (urine)
• Cell Line
• Citrulline (metabolism)
• Cricetinae
• Female
• Fibroblasts (enzymology)
• Genes, Recessive
• Genetic Complementation Test
• HeLa Cells
• Humans
• Hybrid Cells
• Ligases (deficiency)
• Liver (enzymology)
• Lyases (metabolism)
• Male
• Renal Aminoacidurias (metabolism)