Interplay between cholesterol and drug metabolism

Tadeja Rezen, Damjana Rozman, Jean Marc Pascussi, K. Monostory

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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, pregnane X receptor (PXR), constitutive androstane receptor (CAR), vitamin D receptor (VDR), and glucocorticoid receptor (GR) provide a functional cross-talk between the pathways maintaining cholesterol homeostasis and controlling the expression of drug-metabolizing enzymes. These receptors serve as metabolic sensors, resulting in a coordinate regulation of cholesterogenic compounds metabolism and of the defense against xenobiotic and endobiotic toxicity. Herein we present a comprehensive review of functional interactions between cholesterol homeostasis and drug metabolism involving the main nuclear and steroid receptors.

Original languageEnglish
Pages (from-to)146-160
Number of pages15
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1814
Issue number1
DOIs
Publication statusPublished - Jan 2011

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Metabolism
Cholesterol
Homeostasis
Cytochrome P-450 Enzyme System
Pharmaceutical Preparations
Steroid Receptors
Xenobiotics
Cytoplasmic and Nuclear Receptors
Bile Acids and Salts
Vitamin D
Glucocorticoids
Molecules
Cues
Steroid hormones
Sterol Regulatory Element Binding Proteins
Calcitriol Receptors
Ubiquinone
Biosynthetic Pathways
Glucocorticoid Receptors
Metabolic Networks and Pathways

Keywords

  • Bile acid
  • Cholesterol
  • Drug metabolism
  • Glucocorticoid
  • Nuclear receptor
  • SREBP2

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology

Cite this

Interplay between cholesterol and drug metabolism. / Rezen, Tadeja; Rozman, Damjana; Pascussi, Jean Marc; Monostory, K.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1814, No. 1, 01.2011, p. 146-160.

Research output: Contribution to journalArticle

Rezen, Tadeja ; Rozman, Damjana ; Pascussi, Jean Marc ; Monostory, K. / Interplay between cholesterol and drug metabolism. In: Biochimica et Biophysica Acta - Proteins and Proteomics. 2011 ; Vol. 1814, No. 1. pp. 146-160.
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