PXD060653

PXD060653 is an original dataset announced via ProteomeXchange.

Title	Effects of Chronic Alcohol Intake on the Composition of the Ensemble of Drug-Metabolizing Enzymes and Transporters in the Human Liver
Description	In this study, to better understand the mechanisms of the profound impact of alcohol consumption on drug pharmacokinetics, efficacy, and toxicity, we characterized the alcohol-induced changes in the ensemble of drug-metabolizing enzymes and transporters (DMETs) in the human liver by performing global proteomic analysis of human liver microsomes from 94 donors. DMET protein levels were analyzed concerning alcohol consumption, smoking history, and sex using non-parametric tests, which were further strengthened by correlational analysis. To this end, we used a provisional index of alcohol exposure formulated based on the relative abundances of four marker proteins best correlating with the level of alcohol consumption. Alcohol-induced changes in the cytochrome P450 pool include significant increases in CYP2E1, CYP2B6, CYP2J2, and NADPH-cytochrome P450 reductase levels and the lowering of CYP1A2, CYP2C8, CYP2C9, CYP4A11, and cytochrome b5. Changes in UDP-glucuronosyltransferase (UGT) abundances comprise elevated UGT1A6, UGT1A9, and UGT2A1, and reduced UGT1A3, UGT1A4, UGT2B7, UGT2B10, and UGT2B15 levels. Tobacco smokers showed elevated CYP1A2, UGT1A6, and UGT2B4 and reduced FMO3, FMO4, and FMO5 levels, while in females, CYP1A2, UGT2B17, and UGT2B15 levels were lower, and UGT2A3 and STS were higher compared to males. The alcohol-induced changes in the DMET ensemble at the protein level reported herein provide deep insights into how alcohol impacts drug and xenobiotic metabolism.
HostingRepository	PRIDE
AnnounceDate	2025-02-11
AnnouncementXML	Submission_2025-02-10_16:38:05.359.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bhagwat Prasad
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-10 14:52:31	ID requested
⏵ 1	2025-02-10 16:38:05	announced

10.3390/JOX15010020;

submitter keyword: drug metabolism

human liver microsomes

cytochromes P450

alcohol consumption

tobacco smoking

proteomics

alcohol–drug interactions

Bhagwat Prasad
contact affiliation	Professor, Department of Pharmaceutical Sceicnes Washington State University Spokane, WA
contact email	bhagwat.prasad@wsu.edu
lab head
Bhagwat Prasad
contact affiliation	Washington State University
contact email	bhagwat.prasad@wsu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060653
     1. Label: PRIDE project
     2. Name: Effects of Chronic Alcohol Intake on the Composition of the Ensemble of Drug-Metabolizing Enzymes and Transporters in the Human Liver