Phosphatidylethanol in blood as a marker of alcohol abuse

Arthur Varga

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Biological markers offer a way of assessing ethanol intake and determining whether a health problem is alcohol related. This study investigated the use of phosphatidylethanol (PEth) in blood as a new marker of alcohol abuse. PEth is an abnormal phospholipid, formed only in the presence of ethanol via the transphosphatidylation reaction of phospholipase D (PLD). A new HPLC-evaporative light scattering detector (ELSD) method was developed for the analysis of PEth in blood. The method has high precision and analytical specificity with few interferents and a very high biological specificity. Inmoderate drinking (>50 g ethanol/day for several weeks) is required to give detectable PEth. A dose-response between alcohol intake and level of PEth seems to occur. PEth is almost completely compartmentalized in the red blood cell (RBC) fraction of human blood. Chronic alcoholics display a one-compartment elimination of PEth in blood, with a half-life of 4 days and a normalization that takes up to 14 days after end of drinking. PEth is formed in human RBC at physiologically relevant ethanol concentrations (50 mM), with an accumulation rate that is slower compared to rates in other tissues. RBC with high MCV from alcoholics seem to accumulate twice as much PEth compared to RBC with normal MCV from healthy control individuals. Increased PEth formation by phorbol ester TPA and 1-octanol in RBC indicate involvement of protein kinase C (PKC) in PLD-formation of PEth. Enzyme inhibitor studies indicate that PEth in human RBC is metabolized by phosphatidic acid phosphohydrolase. These results support the use of PEth in blood as a reliable long-time state marker of alcohol abuse.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Laboratory Medicine
Supervisors/Advisors
  • [unknown], [unknown], Supervisor, External person
Award date2001 Dec 11
Publisher
ISBN (Print)91-628-5047-4
Publication statusPublished - 2001

Bibliographical note

Defence details

Date: 2001-12-11
Time: 13:00
Place: Segerfalksalen WNC, BMC, Sölvegatan 17, Lund

External reviewer(s)

Name: Helander, Anders
Title: Associate Professor
Affiliation: Karolinska Hospital, Stockholm, Sweden

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The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Medical Neurochemistry (ceased) (LUR000012), Associative Learning (013212013)

Subject classification (UKÄ)

  • Neurology

Free keywords

  • PKC
  • MCV
  • ELSD
  • HPLC
  • red blood cell
  • phospholipase D
  • phosphatidylethanol
  • ethanol
  • alcohol abuse
  • state marker
  • Neurology
  • neuropsychology
  • neurophysiology
  • Neurologi
  • neuropsykologi
  • neurofysiologi

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