溶解素D5和D1通过尿素5'-二酸-葡萄糖基转移酶进行二期代谢
Marina S Nogueira1, Stephanie C Sanchez2, Carol E Milne3
1Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37232-6602, USA.
像RvD5和RvD1这样的专门的亲溶解媒介 (SPM) 通过人肝显微体被代谢成葡萄糖合物. 非类固醇抗炎药物 (NSAIDs) 可以抑制这种新陈代谢,从而影响体内SPM量化.
科学领域:
- 脂质媒介代谢的代谢过程
- 炎症的分辨率 炎症分辨率
- 药理学 药理学是指药理学的学科.
背景情况:
- 专门的亲解决媒介 (SPMs) 能够解决炎症,但它们的新陈代谢尚不清楚.
- 支持炎症的脂质介质被快速代谢.
- SPM可以作为食补充剂,需要了解它们的代谢命运.
研究的目的:
- 为了研究精确研究的SPMs的代谢,特别是resolvin D5 (RvD5) 和resolvin D1 (RvD1).
- 为了确定负责SPM代谢的酶.
- 为了确定非类固醇抗炎药物 (NSAIDs) 对SPM代谢的影响.
主要方法:
- 用人类肝脏显微体 (HLM) 化RvD5和RvD1.
- 使用分析技术识别代谢物.
- 使用特定的尿素5'-二酸-葡萄糖转移酶 (UGT) 异型的酶动力学研究.
- 评估HLM对RvD5和RvD1代谢NSAID的影响.
主要成果:
- RvD5和RvD1很容易被HLM代谢,形成葡萄糖合代谢产物.
- 特定的UGT异型催化RvD5和RvD1.1的葡萄糖化.
- 无 NSAID 抑制RvD5 和RvD1 的代谢由HLM通过循环氧基因酶独立的机制,作为UGT 抑制剂.
结论:
- SPM 在人体肝脏中发生显著的新陈代谢,主要是通过葡萄糖化.
- UGT酶是SPM代谢失活的关键参与者.
- NSAIDs可以通过抑制其新陈代谢来调节体内SPM水平,强调需要考虑药物-酶-介质相互作用以准确地进行体内SPM量化.
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