Antunes F, Salvador A, Pinto R E
Grupo de Bioquímica e Biologia Teóricas, Instituto de Investigação Científica Bento da Rocha Cabral, Lisboa, Portugal.
Free Radic Biol Med. 1995 Nov;19(5):669-77. doi: 10.1016/0891-5849(95)00040-5.
The comparative importance of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and of "classic" glutathione peroxidase (GPx) in the reduction of phospholipid hydroperoxides is unclear. Although GPx activity is 500-fold higher than that of PHGPx in rat liver, the reduction of phospholipid hydroperoxides by glutathione (GSH) through GPx may be strongly limited by a low PLA2 activity. We address this issue using a moderately detailed kinetic model of mitochondrial lipid peroxidation in rat liver. The model was based on published data and was subjected to validation as reported in the references. It is analysed by computer simulation and sensitivity analysis. Results suggest that in rat liver mitochondria PHGPx is responsible for almost all phospholipid hydroperoxide reduction. Under physiological conditions, the estimated flux of phospholipid hydroperoxides reduction through PHGPx is about four orders of magnitude higher than the estimated hydrolysis flux through PLA2. On the other hand, virtually all hydrogen peroxide is reduced through GPx. Therefore, a functional complementarity between PHGPx and GPx is suggested. Because the results are qualitatively robust to changes of several orders of magnitude in PLA2 and PHGPx levels, the conclusions may not be limited to mitochondria.
磷脂氢过氧化物谷胱甘肽过氧化物酶（PHGPx）和“经典”谷胱甘肽过氧化物酶（GPx）在还原磷脂氢过氧化物方面的相对重要性尚不清楚。尽管在大鼠肝脏中GPx活性比PHGPx高500倍，但谷胱甘肽（GSH）通过GPx还原磷脂氢过氧化物的过程可能会受到低磷脂酶A2（PLA2）活性的强烈限制。我们使用大鼠肝脏线粒体脂质过氧化的适度详细动力学模型来解决这个问题。该模型基于已发表的数据，并按照参考文献中的报告进行了验证。通过计算机模拟和敏感性分析对其进行分析。结果表明，在大鼠肝脏线粒体中，PHGPx几乎负责所有磷脂氢过氧化物的还原。在生理条件下，通过PHGPx还原磷脂氢过氧化物的估计通量比通过PLA2的估计水解通量高约四个数量级。另一方面，几乎所有过氧化氢都是通过GPx还原的。因此，提示PHGPx和GPx之间存在功能互补性。由于结果在定性上对PLA2和PHGPx水平几个数量级的变化具有稳健性，这些结论可能不限于线粒体。
