James Richard W, Deakin Sara P
Clinical Diabetes Unit, Division of Endocrinology, Diabetes, and Nutrition, Faculty of Medicine, University Hospital, 24 Rue Micheli-du-Crest, 1211 Geneva 14, Switzerland.
Free Radic Biol Med. 2004 Dec 15;37(12):1986-94. doi: 10.1016/j.freeradbiomed.2004.08.012.
The association of paraoxonase-1 (PON1) with high-density lipoproteins (HDL) is a prerequisite for maintaining normal serum activity of the enzyme. The lipoprotein furnishes an amphipathic environment to shield the hydrophobic, N-terminal region of the enzyme, and such an environment may also be necessary for interaction of PON1 with its substrates. HDL provides the optimal physiological acceptor complex, in terms of both stimulating PON1 secretion and stabilizing the secreted peptide. Lipid and peptide components of HDL contribute to these effects, such that modulating HDL composition influences PON1 activity and function. In this context, understanding how PON1 associates with HDL, what governs the association, and the mechanism by which the PON1-HDL complex exerts its antioxidant function is of particular physiological relevance. Moreover, HDL is subject to substantial compositional variations under both normal and pathological metabolic conditions. It has implications for the influence of the enzyme on cardiovascular risk, as normal enzyme activity may not correlate with optimal functional (antioxidant) efficiency. We review evidence that HDL lipid and protein components interact to promote PON1 secretion and maintain serum enzyme activity. Emerging data on how the enzyme associates with HDL are discussed, and the consequences for PON1 function of modifications to HDL are outlined. Finally, we highlight questions concerning the HDL-PON1 association that remain unanswered but are of particular importance in defining PON1 efficiency.
对氧磷酶-1（PON1）与高密度脂蛋白（HDL）的结合是维持该酶正常血清活性的前提条件。这种脂蛋白提供了一个两亲性环境，以保护该酶的疏水N端区域，而且这样的环境对于PON1与其底物的相互作用可能也是必需的。就刺激PON1分泌和稳定分泌的肽而言，HDL提供了最佳的生理受体复合物。HDL的脂质和肽成分促成了这些效应，因此调节HDL的组成会影响PON1的活性和功能。在这种情况下，了解PON1如何与HDL结合、是什么控制这种结合以及PON1-HDL复合物发挥其抗氧化功能的机制具有特殊的生理意义。此外，在正常和病理代谢条件下，HDL的组成都会发生很大变化。这对该酶对心血管风险的影响具有重要意义，因为正常的酶活性可能与最佳的功能（抗氧化）效率不相关。我们综述了HDL的脂质和蛋白质成分相互作用以促进PON1分泌并维持血清酶活性的证据。讨论了关于该酶如何与HDL结合的新数据，并概述了HDL修饰对PON1功能的影响。最后，我们强调了关于HDL-PON1结合的一些尚未得到解答但在定义PON1效率方面特别重要的问题。
