Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Trends Endocrinol Metab. 2019 Aug;30(8):505-519. doi: 10.1016/j.tem.2019.04.009. Epub 2019 Jun 10.
In addition to supporting cellular energetic demands and providing building blocks for lipid synthesis, fatty acids (FAs) are precursors of potent signaling molecules. In particular, the presence of conjugated double bonds on the fatty-acyl chain provides a preferential target for nitration generating nitro-FAs (NO-FAs). The formation of NO-FAs is a nonenzymatic process that requires reactive nitrogen species and occurs locally at the site of inflammation or during gastric acidification. NO-FAs are electrophilic and display pleiotropic signaling actions through reversible protein alkylation. This review focuses on the endogenously formed NO-FAs' mechanism of absorption, systemic distribution, signaling, and preclinical models. Understanding the dynamics of these processes will facilitate targeted dietary interventions and further the current pharmacological development aimed at low-grade inflammatory diseases.
除了支持细胞的能量需求和为脂质合成提供构建块外,脂肪酸(FAs)还是强效信号分子的前体。特别是,脂肪酸酰链上共轭双键的存在为硝化生成硝基脂肪酸(NO-FAs)提供了一个优先的靶标。NO-FAs 的形成是一种非酶促过程,需要活性氮物种,并在炎症部位或在胃酸形成过程中局部发生。NO-FAs 具有亲电性,并通过可逆的蛋白质烷化作用显示出多种信号作用。本综述重点介绍内源性形成的 NO-FAs 的吸收、系统分布、信号传递和临床前模型的机制。了解这些过程的动态将有助于有针对性的饮食干预,并进一步推动目前针对低度炎症性疾病的药理学发展。