title: Lap4, a vacuolar aminopeptidase I, is involved in cadmium-glutathione metabolism.
abstract: In Saccharomyces cerevisiae, accumulation of cadmium-glutathione complex in cytoplasm inhibits cadmium absorption, glutathione transferase 2 is required for the formation of the complex and the vacuolar gamma-glutamyl transferase participates of the first step of glutathione degradation. Here, we proposed that Lap4, a vacuolar amino peptidase, is involved in glutathione catabolism under cadmium stress. Saccharomyces cerevisiae cells deficient in Lap4 absorbed almost 3-fold as much cadmium as the wild-type strain (wt), probably due to the lower rate of cadmium-glutathione complex synthesis in the cytoplasm. In wt, but not in lap4 strain, the oxidized/reduced GSH ratio and the Gtt activity increased in response to cadmium, confirming that the mutant is deficient in the synthesis of the complex probably because the degradation of vacuolar glutathione is impaired. Thus, under cadmium stress, Lap4 and gamma-glutamyl transferase seem to work together to assure an efficient glutathione turnover stored in the vacuole.
authors: Departmento de Bioquímica, IQ, UFRJ, 21941-909, Rio de Janeiro, RJ, Brazil.
authors: Paula D B
authors: PD
authors: Adamis
authors: Sergio C
authors: SC
authors: Mannarino
authors: Cristiano J
authors: CJ
authors: Riger
authors: Giselle
authors: G
authors: Duarte
authors: Ana
authors: A
authors: Cruz
authors: Marcos D
authors: MD
authors: Pereira
authors: Elis C A
authors: EC
authors: Eleutherio
mesh_terms: D000626:Aminopeptidases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D002104:Cadmium / Q000378:metabolism* / Q000633:toxicity; D003593:Cytoplasm / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation; D008954:Models, Biological; D016296:Mutagenesis; D009154:Mutation; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology*; D014617:Vacuoles / Q000201:enzymology*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D002104:Cadmium; D005723:gamma-Glutamyltransferase; D000626:Aminopeptidases; C019689:APE1 protein, S cerevisiae; D005978:Glutathione; D010100:Oxygen