Goerig M, Habenicht A J, Schettler G
Klin Wochenschr. 1985 Apr 1;63(7):293-311. doi: 10.1007/BF01731973.
Prostaglandins, thromboxanes, and leukotrienes have been implicated to play an important role in physiology as well as in a growing list of pathophysiologic conditions. These oxidation products of 8.11.14-eicosatrienoic-, 5.8.11.14.-eicosatetraenoic-, and 5.8.11.14.17.-pentaenoic acids have been collectively designated eicosanoids. Many clinically important diseases are associated with altered eicosanoid biosynthesis. Furthermore, a series of hormones are known to induce acutely formation of eicosanoids, suggesting a crucial role in a multitude of tissue responses including phenomena such as secretion, platelet aggregation, chemotaxis, and smooth muscle contraction. The major precursor for the eicosanoids seems to be 5.8.11.14.-eicosatetraenoic acid or arachidonic acid. Virtually all of arachidonic acid however is present in esterified form in complex glycerolipids. Since cyclooxygenase and the lipoxygenases utilize arachidonic acid in its free form, a set of acylhydrolases is required to liberate arachidonic acid from membrane lipids before eicosanoid formation can occur. It became only recently apparent that a minor acidic phospholipid, phosphatidylinositol, comprising only 5%-10% of the phospholipid mass in mammalian cells, plays an important role in arachidonic acid metabolism. Phosphatidylinositol--after phosphorylation to phosphatidylinositolphosphate and phosphatidylinositolbisphosphate--appears to be hydrolyzed by specific phospholipases C generating 1-stearoyl-2-arachidonoyl-diglyceride. Diglyceride serves as substrate for diglyceride lipase to form monoglyceride and free fatty acid. Alternatively diglyceride is phosphorylated by diglyceride kinase yielding phosphatidic acid, which is believed to be reincorporated into phosphatidylinositol. In addition to phosphatidylinositol phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid may contribute to arachidonic acid release. These phospholipids are substrates for phospholipases A2 generating free arachidonic acid and the respective lysophospholipid. Understanding of the biochemistry of arachidonic acid liberation may be critical in developing strategies of pharmacological intervention in a variety of pathological conditions.
前列腺素、血栓素和白三烯被认为在生理学以及越来越多的病理生理状况中发挥重要作用。这些8,11,14-二十碳三烯酸、5,8,11,14-二十碳四烯酸和5,8,11,14,17-二十碳五烯酸的氧化产物统称为类二十烷酸。许多具有临床重要性的疾病都与类二十烷酸生物合成的改变有关。此外，已知一系列激素可急性诱导类二十烷酸的形成，这表明其在包括分泌、血小板聚集、趋化性和平滑肌收缩等多种组织反应中起关键作用。类二十烷酸的主要前体似乎是5,8,11,14-二十碳四烯酸或花生四烯酸。然而，几乎所有的花生四烯酸都以酯化形式存在于复合甘油脂质中。由于环氧化酶和脂氧化酶利用游离形式的花生四烯酸，因此在类二十烷酸形成之前，需要一组酰基水解酶从膜脂质中释放花生四烯酸。直到最近才明显看出，一种仅占哺乳动物细胞磷脂总量5%-10%的次要酸性磷脂——磷脂酰肌醇，在花生四烯酸代谢中起重要作用。磷脂酰肌醇——在磷酸化生成磷脂酰肌醇磷酸和磷脂酰肌醇二磷酸后——似乎被特定的磷脂酶C水解，生成1-硬脂酰-2-花生四烯酰甘油二酯。甘油二酯作为甘油二酯脂肪酶的底物形成甘油单酯和游离脂肪酸。或者，甘油二酯被甘油二酯激酶磷酸化生成磷脂酸，磷脂酸被认为会重新掺入磷脂酰肌醇中。除了磷脂酰肌醇外，磷脂酰胆碱、磷脂酰乙醇胺和磷脂酸也可能有助于花生四烯酸的释放。这些磷脂是磷脂酶A2的底物，可生成游离花生四烯酸和相应的溶血磷脂。了解花生四烯酸释放的生物化学对于制定针对各种病理状况的药理干预策略可能至关重要。
