Oxidation of 15-hydroxyeicosatetraenoic acid and other hydroxy fatty acids by lung prostaglandin dehydrogenase

Abstract

The oxidation of the 15-hydroxy group of prostaglandins of the A, E, and F series by the NAD +-dependent prostaglandin dehydrogenase (PGDH) has been well documented. In addition to prostaglandins, we have observed that the purified lung PGDH also will oxidize 15-HETE to a novel metabolite that was isolated by reverse-phase HPLC and identified by gas chromatography-mass spectrometry as the 15-keto-5,8,11- cis-13- trans-eicosatetraenoic acid (15-KETE). The K m for 15-HETE was 16 μ m, which was 2.5 times lower than the value obtained for PGE 1. In addition to 15-HETE, 5,15-diHETE and 8,15-diHETE also were substrates for the lung PGDH with K m values of 138 and 178 μ m, respectively. Other hydroxy derivatives of eicosatetraenoic acid that did not have a hydroxy group at carbon atom 15 did not support the PGDH-mediated reduction of NAD +. In addition to the 15-hydroxy derivatives of eicosatetraenoic acid, 12-HHT also was a substrate for the lung enzyme with a K m of 12 μ m. These data indicate that ω6-hydroxy fatty acids, in addition to prostaglandins, are also substrates of the lung NAD +-dependent PGDH and that the enzyme does not require the cyclopentane ring of prostaglandins.