Smith William L, Song Inseok
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing 48824, USA.
Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:115-28. doi: 10.1016/s0090-6980(02)00025-4.
We summarize the enzymological properties of prostaglandin endoperoxide H synthases (PGHs)-1 and -2, the enzymes that catalyze the committed step in prostaglandin biosynthesis. These isoenzymes are closely related structurally and mechanistically. Each catalyzes a peroxidase and a cyclooxygenase reaction at spatially separate but neighboring, electronically interrelated active sites. The peroxidase is necessary to activate the cyclooxygenase; oxidation of the heme group of the peroxidase by peroxide leads to oxidation of a cyclooxygenase active site tyrosine. The tyrosine radical abstracts hydrogen from arachidonic acid to form an arachidonate radical which reacts sequentially with two oxygen molecules forming the intermediate product PGG2. PGG2 is then reduced by the peroxidase activity to PGH2. Based on the crystal structure of PGHS-1 arachidonate complex, it is now possible to envision how arachidonate is bound and oxygenation occurs. Recently, it has become possible to distinguish kinetically between the cyclooxygenase and peroxidase suicide inactivation reactions.
我们总结了前列腺素内过氧化物H合酶（PGH）-1和-2的酶学特性，这两种酶催化前列腺素生物合成中的关键步骤。这些同工酶在结构和机制上密切相关。每种酶在空间上分开但相邻、电子相互关联的活性位点催化过氧化物酶和环氧化酶反应。过氧化物酶对于激活环氧化酶是必需的；过氧化物使过氧化物酶的血红素基团氧化，导致环氧化酶活性位点酪氨酸氧化。酪氨酸自由基从花生四烯酸中提取氢形成花生四烯酸自由基，该自由基依次与两个氧分子反应形成中间产物PGG2。然后PGG2通过过氧化物酶活性还原为PGH2。基于PGHS-1花生四烯酸复合物的晶体结构，现在可以设想花生四烯酸是如何结合以及氧合作用是如何发生的。最近，已经能够在动力学上区分环氧化酶和过氧化物酶的自杀失活反应。
