Specificity of the glutathione S-transferases in the conversion of leukotriene A4 to leukotriene C4.
We have synthesized the 5,6-LTA4, 8,9-LTA4, and 14,15-LTA4 as methyl esters by an improved biomimetic method with yields as high as 70-80%. We have investigated the catalytic efficiency of the purified cytosolic glutathione S-transferase (GST) isozymes from rat liver in the conversion of these leukotriene epoxides to their corresponding LTC4 methyl esters. Among various rat liver GST isozymes, the anionic isozyme, a homodimer of Yb subunit, exhibited the highest specific activity. In general, the isozymes containing the Yb subunit showed better activity than the isozymes containing the Ya and/or Yc subunits. Interestingly, all three different LTA4 methyl esters gave comparable specific activities with a given GST isozyme indicating that regiospecificity of GSTs was not the factor in determining their ability to catalyze this reaction. Surprisingly, purified GSTs from sheep lung and seminal vesicles showed little activity toward these leukotriene epoxides, indicating a lack of the counterpart of rat liver anionic GST isozyme in these tissues.
Chang
M
M
Department of Veterinary Science, Pennsylvania State University, University Park 16802.
Rao
M K
MK
Reddanna
P
P
Li
C H
CH
Tu
C P
CP
Corey
E J
EJ
Reddy
C C
CC
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D017572:Leukotriene A4; D008099:Liver / Q000201:enzymology; D051381:Rats; D013189:SRS-A / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013379:Substrate Specificity
D001095:Arachidonic Acids; D007527:Isoenzymes; D017572:Leukotriene A4; D013189:SRS-A; D005982:Glutathione Transferase