Evidence from heterologous expression of glutathione S-transferases A and A1 of the plaice (Pleuronectes platessa) that their endogenous role is in detoxification of lipid peroxidation products.
cDNA clones for glutathione S-transferases A (GST-A) and A1 (GST-A1) from plaice (Pleuronectes platessa) were expressed as N-terminally 6XHis tagged proteins in Escherichia coli and purified to homogeneity from Ni-NTA silica. GST-A was an efficient catalyst for conjugation of unsaturated alkenals derived from peroxidation of polyunsaturated fatty acids with the highest activity observed with trans-non-2-enal (8 micromol min(-1) mg(-1)). GST-A1 was a very efficient Se-independent glutathione peroxidase with an activity towards cumene hydroperoxide of 25 micromol min(-1) mg(-1). Although the enzymes exhibited moderately high activities towards the model substrate 1-chloro-2,4-dinitrobenzene (CDNB) they exhibited little or no activity towards other common prototypical xenobiotic substrates. Together with data for ontogeny, tissue distribution and inducibility of these enzymes, we contend that a primary function of these enzymes is protection from the harmful effects of lipid peroxidation products generated naturally or exacerbated by xenobiotic exposure.
Martinez-Lara
Esther
E
University of Caen, Spain.
Leaver
Michael
M
George
Stephen
S
D000818:Animals; D001711:Biotransformation; D018076:DNA, Complementary / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005432:Flounder / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000235:genetics* / Q000494:pharmacology*; D015227:Lipid Peroxidation; D014018:Tissue Distribution; D015262:Xenobiotics / Q000009:adverse effects* / Q000378:metabolism*
D018076:DNA, Complementary; D005231:Fatty Acids, Unsaturated; D015262:Xenobiotics; D005982:Glutathione Transferase