OXIDATION OF 15-HYDROXYEICOSATETRAENOIC ACID AND OTHER HYDROXY FATTY-ACIDS BY LUNG PROSTAGLANDIN DEHYDROGENASE
OXIDATION OF 15-HYDROXYEICOSATETRAENOIC ACID AND OTHER HYDROXY FATTY-ACIDS BY LUNG PROSTAGLANDIN DEHYDROGENASE
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DOI：
10.1016/0003-9861(87)90589-3
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发表时间：
1987-09-01
影响因子：
3.9
通讯作者：
OKITA, RT
中科院分区：
文献类型：
--
作者：
BERGHOLTE, JM;SOBERMAN, RJ;OKITA, RT
NAD+-依赖性前列腺素脱氢酶（PGDH）对A、E和F系列野牡丹素的15-羟基的氧化作用已得到充分证明。除了洋地黄素外，我们还观察到纯化的肺PGDH还将15-HETE氧化为新的代谢物，该代谢物通过反相HPLC分离并通过气相色谱-质谱法鉴定为15-酮基-5，8，11-顺式-13-反式-二十碳四烯酸（15-KETE）。15-HETE的Km为16 μ M，比PGE 1获得的值低2.5倍。除了15-HETE之外，5，15-diHETE和8，15-diHETE也是肺PGDH的底物，Km值分别为138和178 μ M。在碳原子15处不具有羟基的二十碳四烯酸的其他羟基衍生物不支持PGDH介导的NAD+还原。除了二十碳四烯酸的15-羟基衍生物外，12-HHT也是肺酶的底物，Km为12 μ M。这些数据表明，除了野牡丹素外，ω 6-羟基脂肪酸也是肺NAD+依赖性PGDH的底物，并且该酶不需要野牡丹素的环戊烷环。
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 .mu.M, 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 .mu.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 Km of 12 .mu.M. 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.