Costa Lucio G, Vitalone Annabella, Cole Toby B, Furlong Clement E
Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105, USA.
Biochem Pharmacol. 2005 Feb 15;69(4):541-50. doi: 10.1016/j.bcp.2004.08.027.
Paraoxonase 1 (PON1) is a serum enzyme closely associated with high density lipoprotein (HDL). PON1 hydrolyzes several organophosphorus compounds used as insecticides, as well as nerve agents; it metabolizes toxic oxidized lipids associated with both low density lipoprotein (LDL) and HDL; and it can hydrolyze a number of lactone-containing pharmaceutical compounds, inactivating some, while activating others. Serum PON1 activity in a given population can vary by 40-fold. Though most of this variation can be explained by polymorphisms in the coding region (Q192R) and the 5' regulatory region (T-108C), modulation of PON1 by a variety of other factors should be taken into account, including other polymorphisms recently discovered but not yet characterized. This paper examines the major factors (environmental chemicals, drugs, smoking, alcohol, diet, age, disease conditions) that have been shown to modulate PON1 activity in either direction. As PON1 plays a protective role in organophosphate toxicity, and, because of its antioxidant capacity, in cardiovascular disease, a better understanding of how PON1 can be modulated by environmental factors has potential toxicological and clinical consequences.
对氧磷酶1（PON1）是一种与高密度脂蛋白（HDL）密切相关的血清酶。PON1可水解多种用作杀虫剂的有机磷化合物以及神经毒剂；它能代谢与低密度脂蛋白（LDL）和HDL相关的有毒氧化脂质；并且它可以水解一些含内酯的药物化合物，使一些药物失活，同时激活另一些药物。特定人群中的血清PON1活性可能相差40倍。尽管这种差异大部分可以由编码区（Q192R）和5'调控区（T - 108C）的多态性来解释，但还应考虑多种其他因素对PON1的调节作用，包括最近发现但尚未明确特征的其他多态性。本文研究了已被证明可双向调节PON1活性的主要因素（环境化学物质、药物、吸烟、饮酒、饮食、年龄、疾病状况）。由于PON1在有机磷中毒中起保护作用，并且因其抗氧化能力在心血管疾病中也起保护作用，所以更好地了解环境因素如何调节PON1具有潜在的毒理学和临床意义。
