PT  - JOURNAL ARTICLE
AU  - Dostal, L A
AU  - Guthenberg, C
AU  - Mannervik, B
AU  - Bend, J R
TI  - Stereoselectivity and regioselectivity of purified human glutathione transferases pi, alpha-epsilon, and mu with alkene and polycyclic arene oxide substrates.
DP  - 1988 May 01
TA  - Drug Metabolism and Disposition
PG  - 420--424
VI  - 16
IP  - 3
4099  - http://dmd.aspetjournals.org/content/16/3/420.short
4100  - http://dmd.aspetjournals.org/content/16/3/420.full
SO  - Drug Metab Dispos1988 May 01; 16
AB  - The stereoselectivities of three biochemically distinct human glutathione transferases, the acidic isoenzyme (pi) purified from placenta and the basic (alpha-epsilon) and the near-neutral (mu) isoenzymes purified from liver, were determined with (+/-)-benzo(a)pyrene-4,5-oxide, pyrene-4,5-oxide, and (+/-)-styrene-7,8-oxide as substrates. Transferase mu was highly selective (greater than 95%) for reaction of glutathione with R-configured oxirane carbon atoms of (+/-)-benzo(a)pyrene-4,5-oxide and pyrene-4,5-oxide, whereas transferase pi was highly stereoselective (greater than 95%) for S-configured epoxide carbon atoms of (+/-)-benzo(a)pyrene-4,5-oxide and pyrene-4,5-oxide. The basic transferases (alpha-epsilon) showed relatively low stereoselectivity with these polycyclic arene oxide substrates; glutathione reaction at R-configured oxirane carbons was preferred, but only by about 2-fold. With (+/-)-benzo(a)pyrene-4,5-oxide as substrate, transferases mu and alpha-epsilon were enantioselective for (4R,5S)-benzo(a)pyrene-4,5-oxide (about 6-fold), whereas transferase pi showed little enantioselectivity. With (+/-)-styrene-7,8-oxide as substrate, transferases mu and pi were selective for (7S)-styrene-7,8-oxide, but this enantioselectivity was not great (1.3- to 1.8-fold); enantioselectivity could not be accurately determined with alpha-epsilon due to the low enzymatic turnover. Transferase pi selectively catalyzed the reaction of glutathione with the benzylic oxirane carbon (C-7) of (+/-)-styrene-7,8-oxide whereas alpha-epsilon preferentially catalyzed reaction with the terminal epoxide carbon (C-8) atom.(ABSTRACT TRUNCATED AT 250 WORDS)