Yan Pan, Eng Ong Chin, Yu Chieng Jin
Department of Biomedical Science, University of Nottingham Malaysia Campus, Jalan Broga, Semenyih 43500, Selangor, Malaysia.
School of Pharmacy, International Medical University, Bukit Jalil 57000, Wilayah Persekutuan Kuala Lumpur, Malaysia.
Curr Drug Metab. 2018;19(11):917-929. doi: 10.2174/1389200219666180528090237.
Cytochrome P450 2S1 (CYP2S1) is one of the 'orphan' CYPs, which is expressed primarily among extra-hepatic tissues and it is inducible by dioxin. Although the contribution of extra-hepatic CYPs in drug metabolism is considered less significant, they play more important roles in leading to in situ toxicity in organs with higher expression.
A non-systemic search was performed to review articles relevant to CYP2S1 in literature. This review will update the findings related to the expression and regulation of CYP2S1 gene and protein, substrate profiles and metabolism mechanisms, genetic polymorphisms, and their association with diseases.
The expression of CYP2S1 was mainly in the epithelium of portal of entry organs such as respiratory and gastrointestinal tract. Aryl Hydrocarbon Receptor (AHR) is believed to be partly involved in the induction of CYP2S1. CYP2S1 was found to activate and deactivate pro-drugs which resulted in toxicity and detoxification of carcinogens. The current knowledge of the endogenous functions of CYP2S1 is largely related to cell proliferation and lipid metabolisms. Several polymorphic alleles of CYP2S1 have been reported and documented to date.
Molecular-based investigations should be performed to better understand the regulation mechanism of CYP2S1 in various cells and tissues. It is pivotal to establish optimum expression and incubation systems in vitro to elucidate the substrate specificity of CYP2S1 and characterise the genetic consequences of variant CYP2S1 in vitro.
细胞色素P450 2S1（CYP2S1）是“孤儿”细胞色素P450之一，主要在肝外组织中表达，且可被二噁英诱导。尽管肝外细胞色素P450在药物代谢中的作用被认为不太显著，但它们在高表达器官的原位毒性形成中发挥着更重要的作用。
进行了非系统性检索以回顾文献中与CYP2S1相关的文章。本综述将更新与CYP2S1基因和蛋白的表达与调控、底物谱和代谢机制、基因多态性及其与疾病的关联相关的研究结果。
CYP2S1的表达主要在呼吸和胃肠道等进入门户器官的上皮中。芳基烃受体（AHR）被认为部分参与了CYP2S1的诱导。发现CYP2S1可激活和失活前体药物，从而导致致癌物的毒性和解毒作用。目前关于CYP2S1内源性功能的认识很大程度上与细胞增殖和脂质代谢有关。迄今为止，已报道并记录了CYP2S1的几个多态性等位基因。
应开展基于分子的研究，以更好地了解CYP2S1在各种细胞和组织中的调控机制。在体外建立最佳表达和孵育系统以阐明CYP2S1的底物特异性并在体外表征CYP2S1变体的遗传后果至关重要。
