Oxidation of 15-hydroxyeicosatetraenoic acid and other hydroxy fatty acids by lung prostaglandin dehydrogenase.
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 Km for 15-HETE was 16 microM, which was 2.5 times lower than the value obtained for PGE1. In addition to 15-HETE, 5,15-diHETE and 8,15-diHETE also were substrates for the lung PGDH with Km values of 138 and 178 microM, 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 Km of 12 microM. These data indicate that omega 6-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.
Bergholte
J M
JM
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226.
Soberman
R J
RJ
Hayes
R
R
Murphy
R C
RC
Okita
R T
RT
D000818:Animals; D006880:Hydroxy Acids / Q000378:metabolism*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D011817:Rabbits; D013379:Substrate Specificity
D006880:Hydroxy Acids; D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase