7-oxo-C and 7-beta-HC pathways

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); see https://www.wikipathways.org/instance/WP4545, 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); described in this pathway, 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 describes Figure 4 and 5 from Griffiths et al. 2020 and was extended with disease information.

胆甾醇及其甾醇前体（如7-脱氢胆固醇（7-DHC）或去氢胆甾醇）的氧化衍生物构成了类氧固醇化合物群体。类氧固醇的形成机制有三：1）酶促途径（甾醇代谢的初始步骤，作为形成甾体激素、胆汁酸和1,25-二羟基维生素D3的中间体）；详见https://www.wikipathways.org/instance/WP4545，2）非酶促途径，通过与活性氧物种（ROS）相互作用，提供了第二类代谢物（该类代谢物还包括从饮食中摄入的氧化胆固醇分子）；详见本途径描述，以及3）由肠道微生物群生成并通过肠肝循环吸收。既往认为类氧固醇为非活性代谢中间体，然而，近期研究已确立这些代谢物在胆固醇稳态中发挥作用，可作为核受体和G蛋白偶联受体的配体，并作为疾病生物标志物（例如尼曼-匹克病）。本途径描述了Griffiths等人在2020年的图4和5，并扩展了疾病信息。