(S)-Preferential detoxification of 4-hydroxy-2(E)-nonenal enantiomers by hepatic glutathione S-transferase isoforms in guinea-pigs and rats

In guinea-pig liver cytosol, racemic 4-hydroxy-2(E)-nonenal (HNE), a reacti ve and highly toxic product released from biomembranes by lipid peroxidatio n, was detoxified (S)preferentially by GSH conjugation mediated by glutathi one S-transferases (GSTs) and (R)-preferentially by NAD(+)-dependent oxidat ion mediated by aldehyde dehydrogenase (ALDH), The GST-mediated detoxificat ion of the HNE enantiomers proceeded at much higher rates than that mediate d by ALDH in guinea-pig liver cytosol. All the major guinea-pig GSTs, A1-1, M1-1, M1-2 and M1-3*, isolated from guinea-pig liver cytosol also catalyse d the (S)-preferential conjugation of the HNE enantiomers. The liver and ot her major tissues of guinea-pigs had no immunologically detectable level of a putative GSTA4-4 orthologue, which exists as a minor GST protein in rat, mouse and human livers and exhibits extremely high catalytic activity towa rds HNE, All the hepatic rat GSTs, Al-1(2), Al-3, A4-4, M1-1, M1-2 and M2-2 , also catalysed the (S)-preferential conjugation of HNE enantiomers.