Oxysterols derived from cholesterol

The Oxysterol group of compounds are oxygenated derivatives of cholesterol or its sterol precursors, e.g. 7-dehydrocholesterol (7-DHC) or desmosterol. There are three mechanisms leading to the formation of oxysterols: 1) Enzymatically (first steps of sterol metabolism, being intermediates for the formation of steroid hormones, bile acids and 1,25-dihydroxyvitamin D3), 2) Non-enzymatically by encountering reactive oxygen species (ROS), providing a second pool of metabolites (this pool also includes oxidized cholesterol molecules taken in from diet), see https://www.wikipathways.org/instance/WP5064, and 3) Generation by the gut microflora and uptake through the enterohepatic circulation. Previously oxysterols where though to be inactive metabolic intermediates, however recent findings have established that these metabolites are involved in cholesterol homoeostasis, can be ligands to nuclear and G protein-coupled receptors and biomarkers of diseases (for example Niemann-Pick disease). This pathway drawing was inspired by Figure 3 of the review article by Griffiths et al. 2016, and has been extended with immune system, receptor agonists, steroidal alkaloid and biomarker information from the same paper. This pathway has been updated with Figure 1 from Griffiths et al. 2020 (green areas), Figure 2 (yellow area) and Figure 3 (blue area).

胆甾醇类化合物氧甾醇组分为胆固醇或其甾醇前体的氧化衍生物，例如7-脱氢胆固醇（7-DHC）或去甲甾醇。氧甾醇的形成机制主要包括三种：1）酶促反应（甾醇代谢的初始步骤，为甾体激素、胆汁酸和1,25-二羟基维生素D3的形成提供中间体），2）非酶促反应，通过与活性氧物种（ROS）相互作用，形成代谢物的第二库（此库还包括从饮食中摄入的氧化胆固醇分子），详见https://www.wikipathways.org/instance/WP5064，以及3）由肠道微生物群产生并通过肠肝循环摄取。过去认为氧甾醇是无活性的代谢中间体，然而最新的研究发现，这些代谢物参与胆固醇稳态的维持，可作为核受体和G蛋白偶联受体的配体，并作为疾病的生物标志物（例如尼曼-匹克病）。此通路图灵感来源于Griffiths等人在2016年发表的综述文章中的图3，并在此基础上扩展了免疫系统、受体激动剂、甾体生物碱和生物标志物信息。此通路图已根据Griffiths等人在2020年的图1（绿色区域）、图2（黄色区域）和图3（蓝色区域）进行更新。