Skip navigation
Skip navigation

Functional polymorphism of human glutathione transferase A3: effects on xenobiotic metabolism and steroid biosynthesis

Tetlow, Natasha; Coggan, Marjorie; Casarotto, Marco; Board, Philip

Description

The alpha class glutathione transferase GSTA3-3 is involved in steroid biosynthesis and the metabolism of some xenobiotics. A bioinformatics approach was utilized to identify novel coding region polymorphisms in the glutathione transferase A3 gene (GSTA3). We describe an I71L polymorphism in GSTA3 that occurs at a low frequency in African populations. The activity of the leucine containing isoform was significantly reduced in a range of glutathione- conjugating reactions due to a diminished...[Show more]

dc.contributor.authorTetlow, Natasha
dc.contributor.authorCoggan, Marjorie
dc.contributor.authorCasarotto, Marco
dc.contributor.authorBoard, Philip
dc.date.accessioned2015-12-13T23:07:43Z
dc.identifier.issn1744-6872
dc.identifier.urihttp://hdl.handle.net/1885/86323
dc.description.abstractThe alpha class glutathione transferase GSTA3-3 is involved in steroid biosynthesis and the metabolism of some xenobiotics. A bioinformatics approach was utilized to identify novel coding region polymorphisms in the glutathione transferase A3 gene (GSTA3). We describe an I71L polymorphism in GSTA3 that occurs at a low frequency in African populations. The activity of the leucine containing isoform was significantly reduced in a range of glutathione- conjugating reactions due to a diminished affinity for reduced glutathione, indicating that this allele could be implicated in disease caused by oxidative stress in steroidogenic tissue. By contrast, the Δ5-androsten- 3,17-dione isomerase activity of GSTA3-3 was not affected by this substitution, indicating that there is no direct effect on steroid synthesis. However, the L71 isoform displayed diminished stability at 45°C. If this relative instability is mirrored in vivo, testosterone and progesterone synthesis may be affected in individuals carrying this allele.
dc.publisherLippincott Williams & Wilkins
dc.sourcePharmacogenetics and Genomics
dc.subjectKeywords: complementary DNA; delta 5 androsten 3,17 dione isomerase; glutathione transferase; glutathione transferase a3; leucine; testosterone; unclassified drug; allele; amino acid substitution; article; bioinformatics; calcium transport; drug effect; gene freque EST; Glutathione; Polymorphism; Transferases
dc.titleFunctional polymorphism of human glutathione transferase A3: effects on xenobiotic metabolism and steroid biosynthesis
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume14
dc.date.issued2004
local.identifier.absfor111599 - Pharmacology and Pharmaceutical Sciences not elsewhere classified
local.identifier.ariespublicationMigratedxPub15160
local.type.statusPublished Version
local.contributor.affiliationTetlow, Natasha, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationCoggan, Marjorie, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationCasarotto, Marco, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBoard, Philip, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage657
local.bibliographicCitation.lastpage663
local.identifier.doi10.1097/00008571-200410000-00003
dc.date.updated2016-02-24T09:47:27Z
local.identifier.scopusID2-s2.0-6944243913
CollectionsANU Research Publications

Download

File Description SizeFormat Image
01_Tetlow_Functional_polymorphism_of_2004.pdf123.68 kBAdobe PDF    Request a copy


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator