RT Journal Article
SR Electronic
T1 Stereoselectivity and regioselectivity of purified human glutathione transferases pi, alpha-epsilon, and mu with alkene and polycyclic arene oxide substrates.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 420
OP 424
VO 16
IS 3
A1 Dostal, L A
A1 Guthenberg, C
A1 Mannervik, B
A1 Bend, J R
YR 1988
UL http://dmd.aspetjournals.org/content/16/3/420.abstract
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)