CYP8B1
孕烷X受体
胆盐出口泵
小异二聚体伴侣
核受体
生物化学
胆固醇7α羟化酶
胆汁酸
药物代谢
细胞色素P450
CYP27A1
法尼甾体X受体
雄激素受体
生物
有机阴离子转运多肽
化学
新陈代谢
运输机
转录因子
基因
作者
Jyrki J. Eloranta,Gerd A. Kullak‐Ublick
标识
DOI:10.1016/j.abb.2004.09.019
摘要
Drugs and bile acids are taken up into hepatocytes by specialized transport proteins localized at the basolateral membrane, e.g., organic anion transporting polypeptides . Following intracellular metabolism by cytochrome P450 (CYP) enzymes, drug metabolites are excreted into bile or urine via ATP-dependent multidrug resistance proteins (MDR1 and MRPs). Bile acids are excreted mainly via the bile salt export pump (BSEP, ABCB11). The genes coding for drug and bile acid transporters and CYP enzymes are regulated by a complex network of transcriptional cascades, notably by the ligand-activated nuclear receptors FXR, PXR, and CAR and by the ligand-independent nuclear receptor HNF-4alpha. The bile acid synthesizing enzymes CYP7A1, CYP8B1, and CYP27A1 are subject to negative feedback regulation by bile acids, which is partly mediated through the transcriptional repressor SHP. The role of transcriptional cofactors, such as SRC-1 and PGC-1, in mediating the gene-specific effects of individual nuclear receptors is becoming increasingly evident.
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