An alpha class mouse glutathione S-transferase with exceptional catalytic efficiency in the conjugation of glutathione with 7beta, 8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene.

The Journal of Biological Chemistry
X HuS V Singh

Abstract

The kinetics of the conjugation of glutathione (GSH) with anti-7beta, 8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9, 10-tetrahydrobenzo(a)pyrene (anti-BPDE) catalyzed by GSH S-transferase (GST) isoenzymes purified from the liver and forestomach of female A/J mouse has been investigated. The GST isoenzymes studied included an alpha class isoenzyme of forestomach (GST 9.5), alpha class hepatic isoenzymes mGSTA3-3 and mGSTA4-4, pi class hepatic isoenzyme mGSTP1-1, and mu class hepatic isoenzyme mGSTM1-1. When the concentration of (+)-anti-BPDE was varied (5-120 microM) at a fixed GSH concentration (2 mM), linear Lineweaver-Burk plots were observed for each isoenzyme. The kcat values for GST 9.5, mGSTA3-3, mGSTP1-1, mGSTM1-1, and mGSTA4-4 were 2.0, 0.02, 0.40, 0. 05, and 0.01 s-1, respectively, with corresponding Km values of 16, 12, 29, 27, and 49 microM. The catalytic efficiency (kcat/Km) of GST 9.5 in the conjugation of GSH with (+)-anti-BPDE, which is believed to be the ultimate carcinogenic metabolite of benzo(a)pyrene, was about 9-625-fold higher as compared with other mouse GST isoenzymes. These results indicate that GST 9.5 of forestomach is different among mammalian alpha class GSTs because (+)-anti-BPDE has been shown to be a...Continue Reading

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Citations

Nov 5, 1999·Archives of Biochemistry and Biophysics·S K SrivastavaS V Singh
Nov 5, 2013·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Xu ChenWuning Mo
Apr 18, 2002·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Jianxia GuoShivendra V Singh
Jul 5, 2007·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·Dorian RamirezGary M Shaw
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Jun 6, 2019·Chemical Communications : Chem Comm·Aiguo SongHui Chen
Jan 17, 2020·Critical Reviews in Toxicology·Patrick E Hanna, M W Anders
Oct 27, 2017·Journal of the American Chemical Society·Ethan G StoddardAaron T Wright
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