Interplay between cholesterol and drug metabolism

Biochimica Et Biophysica Acta
Tadeja RezenKatalin Monostory


Cholesterol biosynthetic and metabolic pathways contain several branching points towards physiologically active molecules, such as coenzyme Q, vitamin D, glucocorticoid and steroid hormones, oxysterols, or bile acids. Sophisticated regulatory mechanisms are involved in maintenance of the homeostasis of not only cholesterol but also other cholesterogenic molecules. In addition to endogenous cues, cholesterol homeostasis needs to accommodate also to exogenous cues that are imported into the body, such as chemicals and medications. Steroid and nuclear receptors together with sterol regulatory element-binding protein (SREBP) mediate the fine tuning of biosynthetic and metabolic routes as well as transports of cholesterol and its derivatives. Similarly, drug/xenobiotic metabolism is the subject to the feedback regulation of cytochrome P450 enzymes and transporters. The regulatory mechanisms that maintain the homeostasis of cholesterogenic molecules and are involved in drug metabolism share similarities. Cholesterol and cholesterogenic compounds (bile acids, glucocorticoids, vitamin D, etc.) regulate the xenosensor signaling in drug-mediated induction of the major drug-metabolizing cytochrome P450 enzymes. The key cellular receptors,...Continue Reading


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