Catabolism of 4‐hydroxynonenal in the rat liver via omega‐ and omega‐1 oxidation (959.2)

Abstract

In addition to our previous finding on the catabolism of 4‐hydroxynonenal (HNE), 3 novel catabolic pathways of HNE were identified in the perfused rat liver by using the combination of metabolomics studies and isotopic analysis. First pathway, omega oxidation of HNE forms 4,9‐dihydroxynonanoate that is further oxidized to 4‐hydroxynonanedioate. The catabolic degradation of 4‐hydroxynonanedioate started from C‐9 to 4‐hydroxyheptanedioyl‐CoA, 2‐hydroxyglutaryl‐CoA, 2‐hydroxyglutarate that enters citric acid cycle via 2‐ketoglutarate. The conversion of 2‐hydroxyglutarate to 2‐ketoglutarate is coupled by the reduction of succinic semialdehyde to 4‐hydroxybutyrate. This whole pathway was confirmed by perfused with (un)labeled 4‐ hydroxyheptanedioate and 2‐hydroxyglutarate, respectively. The second and third pathways are two parallel pathways of degradation of 4,8 ‐ dihydroxynonanoate that is omega‐1 hydroxylation product of HNE. Two parallel catabolic pathways of 4,8‐dihydroxynonanoate follow the same pathways that we reported earlier on HNE catabolism. Rat heart and brain have little activity of HNE omega‐ and omega‐1 oxidation by in vivo and in vitro experiment.