Phosphatidylethanol in blood as a marker of alcohol abuse

University dissertation from Dept of Medical Neurochemistry, Lund University Hospital, SE-221 85 Lund, Sweden

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.

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