Volume 104, Issue 3 p. 515-524
Article

Protein Abundance of Clinically Relevant Drug-Metabolizing Enzymes in the Human Liver and Intestine: A Comparative Analysis in Paired Tissue Specimens

Marek Drozdzik

Corresponding Author

Marek Drozdzik

Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland

Correspondence: Marek Drozdzik ([email protected])Search for more papers by this author
Diana Busch

Diana Busch

Department of Clinical Pharmacology, University Medicine of Greifswald, Greifswald, Germany

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Joanna Lapczuk

Joanna Lapczuk

Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland

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Janett Müller

Janett Müller

Department of Clinical Pharmacology, University Medicine of Greifswald, Greifswald, Germany

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Marek Ostrowski

Marek Ostrowski

Department of General and Transplantation Surgery, Pomeranian Medical University, Szczecin, Poland

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Mateusz Kurzawski

Mateusz Kurzawski

Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland

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Stefan Oswald

Stefan Oswald

Department of Clinical Pharmacology, University Medicine of Greifswald, Greifswald, Germany

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First published: 05 December 2017
Citations: 99

Abstract

This work revises and complements existing findings on the distribution of drug-metabolizing enzymes in the first-pass effect organs. We explored gene expression (quantitative polymerase chain reaction) and protein abundance (liquid chromatography/ tandem mass spectrometry) of CYP1A2, CYP2B6, CYP2C8/9/19, CYP2D6, CYP2E1, CYP3A4/5, UGT1A1/3, UGT2B7/15 in the liver, duodenum, jejunum, ileum, and colon in paired tissues from nine organ donors. All proteins were detected in the liver, but in the intestine CYP2C9/19, CYP2D6, CYP3A4/5, UGT1A1/3, and UGT2B7 were found. CYP3A4 showed comparable abundance in the liver and jejunum, whereas other enzymes were markedly higher in the hepatic tissue. Nearly all detected enzymes showed their highest abundance in the jejunum. Significant correlations between mRNA and protein levels in liver or intestine were found for most enzymes. CYP3A4 and CYP3A5 protein abundance, but not other enzymes, were significantly correlated in the liver and the small intestine. Our data may contribute to an improved understanding of hepatic and intestinal drug metabolism.

CONFLICT OF INTEREST

The authors report no conflicts of interest.