An abnormal phospholipid in rat organs after ethanol treatment

Alling, Christer; Gustavsson, Lena; Änggård, Erik

doi:10.1016/0014-5793(83)80474-8

Cited by 138 publications

(61 citation statements)

References 8 publications

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“…The in vivo production of phosphatidylethanol in kidney, liver, and brain tissues has also been reported independently by Alling et al (6) for rats receiving toxic doses of ethanol.…”

mentioning

confidence: 74%

“…With respect to the alcoholic subjects whose phosphatidylethanol production potential overlaps the levels exhibited by the controls (i.e., intervals [4][5][6][7][8][9][10][11][12], it can be added that recent experiments have revealed that phosphatidylethanol is subject to a unique metabolism in certain cell systems. This metabolism is carried out by a steroid-inducible pathway, yields chemically reactive derivatives of phosphatidylethanol, and may be important to the regulation of phosphatidylethanol levels under conditions of endogenous stimulation.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of phosphatidylethanol--a potential marker for adult males at risk for alcoholism.

Mueller

Fleming

Lemahieu

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Phosphatidylethanol, whose synthesis is catalyzed by a phospholipase D in a transphosphatidylation reaction, is a unique metabolite of ethanol. Phorbol 12-tetradecanoate 13-acetate, a tumor-promoting phorbol ester and stimulator of protein kinase C, activates this enzyme in peripheral blood lymphocytes. This system has been developed into an assay for measuring the potential of this pathway in human subjects. A pilot study of phosphatidylethanol synthesis in lymphocytes of adult males who have both an alcohol dependency and a family history ofalcoholism has revealed that the average potential for phosphatidylethanol synthesis in this population is significantly elevated over that of control subjects.In the course of investigating the effects of the tumorpromoting phorbol ester, phorbol 12-tetradecanoate 13-acetate (TPA) on the metabolism of [3H]arachidonic acid during the mitogenic activation of lymphocytes, Wrighton et al.(1) discovered that a class of unusual lipid metabolites were rapidly formed in response to TPA. These products were subsequently characterized to be glycerolphospholipids in which the typical head group (i.e., choline, ethanolamine, inositol, or serine) had been replaced by ethanol (2) (Fig. 1) Our finding that the pathway for phosphatidylethanol synthesis could be activated by TPA in human lymphocytes from peripheral blood has opened the way to exploring whether the ability of human subjects to synthesize this unique metabolite of ethanol correlates in any way with the individual's dependency on alcohol. To explore this question, an assay was developed for measuring the induced synthesis of phosphatidylethanol in short-term cultures of human peripheral blood lymphocytes. This test has been used to assess the ability of two groups of males to synthesize phosphatidylethanol: group 1 consisted of 24 nonalcoholic males with no family history of alcoholism in any first degree relatives; and group 2 consisted of 25 males who met the DSM-III (Disease Statistical Manual, version 3, American Psychiatric Association) criteria for alcohol dependence and who also reported an alcoholic parent who met the DSM-III criteria for abuse and/or dependence (7).The results of this pilot study show that adult males with both a personal history of alcohol dependence and a family history of alcoholism (DSM-III criteria) have a significantly greater average ability to synthesize phosphatidylethanol than do their control counterparts. These preliminary findings provide the first evidence that the synthesis of phosphatidylethanol and the regulation of this phospholipase Dcatalyzed pathway may play an important role in alcohol dependency-and may contribute as well to the development of alcohol-related pathology. A molecular and genetic exploration of the components in this pathway is expected to provide new approaches to the therapy and prophylaxis of alcoholism in humans. MATERIALS AND METHODS Assay of Potential for Phosphatidylethanol Synthesis byUsing Human Lymphocytes. Approximately 20 ml of venous blood was...

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“…The in vivo production of phosphatidylethanol in kidney, liver, and brain tissues has also been reported independently by Alling et al (6) for rats receiving toxic doses of ethanol.…”

mentioning

confidence: 74%

Section: Resultsmentioning

confidence: 99%

Synthesis of phosphatidylethanol--a potential marker for adult males at risk for alcoholism.

Mueller

Fleming

Lemahieu

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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“…Phosphatidylethanol (PEth) is another indicator of high alcohol consumption identified some time ago (10,11 ) that so far has received limited clinical interest. PEth is an ethanol-derived phospholipid formed from phosphatidylcholine (PC) in cell membranes by a transphosphatidylation reaction catalyzed by phospholipase D (12 ).…”

mentioning

confidence: 99%

Molecular Species of the Alcohol Biomarker Phosphatidylethanol in Human Blood Measured by LC-MS

2009

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BACKGROUND:The alcohol biomarker phosphatidylethanol (PEth) comprises a group of ethanolderived phospholipids formed from phosphatidylcholine by phospholipase D. The PEth molecular species have a common phosphoethanol head group onto which 2 fatty acid moieties are attached. We developed an electrospray ionization (ESI) LC-MS method for qualitative and quantitative measurement of different PEth species in human blood.

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“…Phosphatidylethanol (PEth) is a direct biomarker of alcohol metabolism that has generated interest in the field of alcoholism research in recent years, as it has been shown to be a highly sensitive and specific indicator of alcohol use and misuse. PEth is a unique phospholipid formed only in the presence of ethanol from phosphatidylcholine, present within membranes of red blood cells, through a metabolic process catalyzed by phospholipase D (Alling, Gustavsson, & Anggard, 1983;Gustavsson & Alling, 1987;Mueller, Fleming, LeMahieu, Lybrand, & Barry, 1988). Human red blood cells do not have the enzymatic machinery to efficiently degrade PEth, causing the accumulation of PEth in the cellular membranes following exposure to ethanol (Aradottir, Moller, & Alling, 2004).…”

mentioning

confidence: 99%

Retrospective assessment of prenatal alcohol exposure by detection of phosphatidylethanol in stored dried blood spot cards: An objective method for determining prevalence rates of alcohol consumption during pregnancy

Baldwin

Jones

et al. 2015

IJADR

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Aims: To analyze the efficacy of screening banked newborn dried blood spots (DBS) for detection of phosphatidylethanol (PEth), a direct alcohol biomarker, with the purpose of performing a retrospective assessment of statewide prevalence rates of alcohol consumption in late pregnancy that results in risky prenatal alcohol exposure.Design: Residual DBS samples collected for newborn screening and stored by a state department of public health were examined for concentrations of PEth. The prevalence of prenatal alcohol exposure, as determined by this direct alcohol biomarker, was compared to prevalence rates of alcohol consumption during pregnancy that have been derived from multiple state-based and national studies using maternal self-report surveys.Setting: DBS cards representative of the general newborn population were collected from multiple hospitals across a single midwestern state. Participants:Two hundred fifty anonymous newborn DBS collected for routine metabolic screening in a midwestern state were requested through the Virtual Repository of Dried Blood Spots. Measures:Concentrations of PEth, a highly specific biomarker of alcohol consumption, were analyzed using a liquid chromatography-tandem mass spectrometry method validated by our laboratory. Findings:Of 250 DBS examined, 4% were positive for PEth (PEth ≥ 8 ng/ml) which is indicative of exposure to maternal alcohol consumption during the last month of pregnancy.Conclusions: Detection of PEth from newborn DBS cards can identify prenatal alcohol exposure and also be used for retrospective surveillance of alcohol consumption during the last three to four weeks of pregnancy, using specimens that are collected for routine metabolic screening and stored by many state health departments.

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An abnormal phospholipid in rat organs after ethanol treatment

Cited by 138 publications

References 8 publications

Synthesis of phosphatidylethanol--a potential marker for adult males at risk for alcoholism.

Synthesis of phosphatidylethanol--a potential marker for adult males at risk for alcoholism.

Molecular Species of the Alcohol Biomarker Phosphatidylethanol in Human Blood Measured by LC-MS

Retrospective assessment of prenatal alcohol exposure by detection of phosphatidylethanol in stored dried blood spot cards: An objective method for determining prevalence rates of alcohol consumption during pregnancy

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