Paraoxonase 1: evolution of the enzyme and of its role in protecting against atherosclerosis.

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current opinion in lipidology Pub Date : 2024-08-01 Epub Date: 2024-06-18 DOI:10.1097/MOL.0000000000000936
Paul Durrington, Handrean Soran
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引用次数: 0

Abstract

Purpose of review: To review the discoveries which led to the concept that serum paraoxonase 1 (PON1) is inversely related to atherosclerotic cardiovascular disease (ASCVD) incidence, how this association came to be regarded as causal and how such a role might have evolved.

Recent findings: Animal models suggest a causal link between PON1 present on HDL and atherosclerosis. Serum PON1 activity predicts ASCVD with a similar reliability to HDL cholesterol, but at the extremes of high and low HDL cholesterol, there is discordance with PON1 being potentially more accurate. The paraoxonase gene family has its origins in the earliest life forms. Its greatest hydrolytic activity is towards lactones and organophosphates, both of which can be generated in the natural environment. It is active towards a wide range of substrates and thus its conservation may have resulted from improved survival of species facing a variety of evolutionary challenges.

Summary: Protection against ASCVD is likely to be the consequence of some promiscuous activity of PON1, but nonetheless has the potential for exploitation to improve risk prediction and prevention of ASCVD.

副氧合酶 1:该酶的演变及其在防止动脉粥样硬化方面的作用。
综述目的:回顾导致血清副氧合酶 1(PON1)与动脉粥样硬化性心血管疾病(ASCVD)发病率成反比关系这一概念的发现、这种关联如何被视为因果关系以及这种作用如何演变而来:动物模型表明,存在于高密度脂蛋白上的 PON1 与动脉粥样硬化之间存在因果关系。血清 PON1 活性预测 ASCVD 的可靠性与高密度脂蛋白胆固醇相似,但在高密度脂蛋白胆固醇过高和过低的极端情况下,PON1 的准确性可能更高。对氧磷酶基因家族起源于最早的生命形式。其最大的水解活性是内酯和有机磷酸酯,这两种物质都可以在自然环境中产生。它对多种底物都有活性,因此它的保存可能是面临各种进化挑战的物种更好地生存的结果。小结:防止 ASCVD 可能是 PON1 某些杂乱活性的结果,但仍有可能被利用来改善 ASCVD 的风险预测和预防。
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来源期刊
Current opinion in lipidology
Current opinion in lipidology 医学-内分泌学与代谢
CiteScore
6.70
自引率
4.50%
发文量
64
审稿时长
6-12 weeks
期刊介绍: With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.
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