Reina Sofia University Hospital, Córdoba, Spain.
Curr Drug Metab. 2009 Oct;10(8):932-45. doi: 10.2174/138920009790274595.
Drug metabolizing enzymes (DME) play a central role in the intestinal absorption/permeability, metabolism, elimination and detoxification of endogenous and exogenous compounds. DME include phase I and II metabolizing enzymes. The hydroxylation activity of phase I DME increases the hydrophilicity of the molecules. The electrophilicity of phase I DME-derived products is reduced via conjugation with endogenous ligands, such as glutathione and glucuronic acid, and facilitates their inactivation and excretion in the bile and/or the urine. The transport system is involved in the cellular input/output of molecules and drugs. Numerous endogenous and exogenous compounds, being the substrates of DME, regulate the expression of DME genes through the activation of a number of nuclear receptors. These nuclear receptors directly or indirectly target different regulatory sequences present in the promoter region of the DME genes. The review describes the activation process of nuclear receptors, as well as their interactions to elucidate the extended cross-talk between them in the regulation of DME.
药物代谢酶（DME）在肠道吸收/通透性、代谢、消除和解毒内源性和外源性化合物中起着核心作用。DME 包括 I 相和 II 相代谢酶。I 相 DME 的羟化活性增加了分子的亲水性。通过与内源性配体（如谷胱甘肽和葡萄糖醛酸）结合，降低了 I 相 DME 衍生产物的亲电性，从而促进其失活并通过胆汁和/或尿液排出。转运系统参与分子和药物的细胞输入/输出。许多内源性和外源性化合物作为 DME 的底物，通过激活许多核受体来调节 DME 基因的表达。这些核受体直接或间接地针对 DME 基因启动子区域中存在的不同调节序列。本文综述了核受体的激活过程及其相互作用，以阐明它们在调节 DME 中的扩展串扰。
