Suppr超能文献

硝酰基脂肪酸的代谢动力学:生成、生物分布、信号传递和药理学。

Nitro-Fatty Acid Logistics: Formation, Biodistribution, Signaling, and Pharmacology.

机构信息

Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

出版信息

Trends Endocrinol Metab. 2019 Aug;30(8):505-519. doi: 10.1016/j.tem.2019.04.009. Epub 2019 Jun 10.

Abstract

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.

摘要

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。

相似文献

1
Nitro-Fatty Acid Logistics: Formation, Biodistribution, Signaling, and Pharmacology.
Trends Endocrinol Metab. 2019 Aug;30(8):505-519. doi: 10.1016/j.tem.2019.04.009. Epub 2019 Jun 10.
2
Nitro Fatty Acids (NO-FAs): An Emerging Class of Bioactive Fatty Acids.
Molecules. 2021 Dec 13;26(24):7536. doi: 10.3390/molecules26247536.
3
Nitro-fatty acid formation and metabolism.
Nitric Oxide. 2018 Sep 1;79:38-44. doi: 10.1016/j.niox.2018.07.003. Epub 2018 Jul 10.
4
Nitro-fatty acids: electrophilic signaling molecules in plant physiology.
Planta. 2021 Nov 13;254(6):120. doi: 10.1007/s00425-021-03777-z.
5
6
Nitro-fatty acid metabolome: saturation, desaturation, beta-oxidation, and protein adduction.
J Biol Chem. 2009 Jan 16;284(3):1461-73. doi: 10.1074/jbc.M802298200. Epub 2008 Nov 17.
7
Nitro-fatty acids in plant signaling: New key mediators of nitric oxide metabolism.
Redox Biol. 2017 Apr;11:554-561. doi: 10.1016/j.redox.2017.01.002. Epub 2017 Jan 10.
8
Protection of nitro-fatty acid against kidney diseases.
Am J Physiol Renal Physiol. 2016 Apr 15;310(8):F697-F704. doi: 10.1152/ajprenal.00321.2015. Epub 2015 Dec 30.
9
Nitro-fatty acid pharmacokinetics in the adipose tissue compartment.
J Lipid Res. 2017 Feb;58(2):375-385. doi: 10.1194/jlr.M072058. Epub 2016 Dec 2.
10
Generation and esterification of electrophilic fatty acid nitroalkenes in triacylglycerides.
Free Radic Biol Med. 2015 Oct;87:113-24. doi: 10.1016/j.freeradbiomed.2015.05.033. Epub 2015 Jun 9.

引用本文的文献

1
Regio- and Stereoselective Synthesis of Nitro-fatty Acids as NRF2 Pathway Activators Working under Ambient or Hypoxic Conditions.
J Med Chem. 2025 Jun 12;68(11):12172-12184. doi: 10.1021/acs.jmedchem.5c00982. Epub 2025 May 26.
2
Nitrated fatty acids protect against acute kidney injury in sickle cell disease.
Blood Adv. 2025 Jun 24;9(12):2886-2890. doi: 10.1182/bloodadvances.2024015038.
3
The emerging significance of furan fatty acids in food, nutrition, and potential therapeutic use.
Food Chem. 2025 Jul 1;479:143759. doi: 10.1016/j.foodchem.2025.143759. Epub 2025 Mar 8.
4
Human glutathione transferases catalyze the reaction between glutathione and nitrooleic acid.
J Biol Chem. 2025 Apr;301(4):108362. doi: 10.1016/j.jbc.2025.108362. Epub 2025 Feb 28.
6
NADPH oxidases: redox regulation of cell homeostasis and disease.
Physiol Rev. 2025 Jul 1;105(3):1291-1428. doi: 10.1152/physrev.00034.2023. Epub 2025 Jan 15.
7
The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.
Chem Rev. 2025 Jan 8;125(1):1-90. doi: 10.1021/acs.chemrev.3c00520. Epub 2024 Dec 16.
8
Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity.
Am J Physiol Endocrinol Metab. 2025 Jan 1;328(1):E69-E91. doi: 10.1152/ajpendo.00256.2024. Epub 2024 Dec 9.
9
Development of nitroalkene-based inhibitors to target STING-dependent inflammation.
Redox Biol. 2024 Aug;74:103202. doi: 10.1016/j.redox.2024.103202. Epub 2024 May 21.
10
A metabolic perspective on nitric oxide function in melanoma.
Biochim Biophys Acta Rev Cancer. 2024 Jan;1879(1):189038. doi: 10.1016/j.bbcan.2023.189038. Epub 2023 Dec 5.

本文引用的文献

1
Nitro-fatty acids protect against steatosis and fibrosis during development of nonalcoholic fatty liver disease in mice.
EBioMedicine. 2019 Mar;41:62-72. doi: 10.1016/j.ebiom.2019.02.019. Epub 2019 Feb 13.
2
Electrophilic nitro-oleic acid reverses obesity-induced hepatic steatosis.
Redox Biol. 2019 Apr;22:101132. doi: 10.1016/j.redox.2019.101132. Epub 2019 Feb 1.
3
Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis.
Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1723-1732. doi: 10.1073/pnas.1817984116. Epub 2018 Dec 17.
4
5
Nitrite and nitrate chemical biology and signalling.
Br J Pharmacol. 2019 Jan;176(2):228-245. doi: 10.1111/bph.14484. Epub 2018 Oct 3.
6
Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling.
Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7768-E7775. doi: 10.1073/pnas.1806239115. Epub 2018 Jul 30.
7
Nitro-fatty acid formation and metabolism.
Nitric Oxide. 2018 Sep 1;79:38-44. doi: 10.1016/j.niox.2018.07.003. Epub 2018 Jul 10.
8
Nitro-fatty acids: New drug candidates for chronic inflammatory and fibrotic diseases.
Nitric Oxide. 2018 Sep 1;79:31-37. doi: 10.1016/j.niox.2018.06.006. Epub 2018 Jun 23.
10
Dynamic role of the transmembrane glycoprotein CD36 (SR-B2) in cellular fatty acid uptake and utilization.
J Lipid Res. 2018 Jul;59(7):1084-1093. doi: 10.1194/jlr.R082933. Epub 2018 Apr 7.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验