title: Human liver microsomal glutathione transferase. Substrate specificity and important protein sites.
abstract: Human liver microsomal glutathione transferase displays the following glutathione peroxidase/transferase activities: dilinoleoylphosphatidylcholine hydroperoxide (0.03 and 0.17 mumol/min.mg, unactivated and N-ethylmaleimide-activated enzyme, respectively), linoleic acid hydroperoxide (0.09 and 0.15 mumol/min.mg), cumene hydroperoxide (0.04 and 3 mumol/min.mg), methyl linoleate ozonide (0.02 and 1.2 mumol/min.mg) and 1-chloro-2,4-dinitrobenzene (1.9 and 24 mumol/min.mg). The activation of glutathione peroxidase activities are much higher than previously observed. The activity towards a phospholipid hydroperoxide is noteworthy since protection against lipid peroxidation has been implied. Methyl linoleate ozonide has not previously been characterised as substrate for any microsomal glutathione transferase. Human liver microsomal glutathione transferase displays an isoelectric point of 9.4 and a structure in agreement with that deduced from the cDNA sequence. Gel electrophoretic analysis shows that proteolytic activation of the human enzyme corresponds to cleavage at Lys-41, thus defining the critical activation site.
authors.affiliation: Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Mosialou
authors.forename: C
authors.initials: C
authors.lastname: Andersson
authors.forename: G
authors.initials: G
authors.lastname: Lundqvist
authors.forename: G
authors.initials: G
authors.lastname: Andersson
authors.forename: T
authors.initials: T
authors.lastname: Bergman
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
authors.forename: R
authors.initials: R
authors.lastname: Morgenstern
mesh_terms: D000596:Amino Acids / Q000032:analysis; D004789:Enzyme Activation; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology*; D008970:Molecular Weight; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D008054:Lipid Peroxides; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase