Phosphatidylethanols (PEth) are a group of

phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

s formed only in the presence of ethanol via the action of

phospholipase D Phospholipase D (PLD) (EC 3.1.4.4; also known as lipophosphodiesterase II, lecithinase D, choline phosphatase; systematic name: phosphatidylcholine phosphatidohydrolase) is an anesthetic-sensitive and mechanosensitive enzyme of the phospholipa ...

(PLD). It accumulates in blood and is removed slowly, making it a useful biomarker for alcohol consumption. PEth is also thought to contribute to the symptoms of

alcohol intoxication Alcohol intoxication, commonly described in higher doses as drunkenness or inebriation, and known in overdose as alcohol poisoning, is the behavior and physical effects caused by recent consumption of Alcohol (drug), alcohol. The technical ter ...

Structure

Chemically, phosphatidylethanols are phospholipids carrying two

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

chains A chain is a serial assembly of connected pieces, called links, typically made of metal, with an overall character similar to that of a rope in that it is flexible and curved in compression but linear, rigid, and load-bearing in tension. A ...

, which are variable in structure, and one

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

ethyl

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

Biosynthesis

When ethanol is present, PLD substitutes ethanol for water and covalently attaches the alcohol as the head group of the phospholipid; hence the name phosphatidylethanol. Normally PLD incorporates water to generate phosphatidic acid (PA); the process is termed transphosphatidylation. PLD continues to generate PA in the presence of ethanol and while PEth is generated and the effects of ethanol transphosphatidlyation are through the generation of the unnatural lipid not depletion of PA.

Biological effects

The lipid accumulates in the human body and competes at agonists sites of

lipid-gated ion channels Lipid-gated ion channels are a class of ion channels whose conductance of ions through the membrane depends directly on lipids. Classically the lipids are membrane resident anionic signaling lipids that bind to the transmembrane domain on the inn ...

contributing to alcohol intoxication. The chemical similarity of PEth to

phosphatidic acid Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty a ...

(PA) and

phosphatidylinositol 4,5-bisphosphate Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...

(PIP2) suggest a likely broad perturbation to

lipid signaling Lipid signaling, broadly defined, refers to any biological cell signaling event involving a lipid messenger that binds a protein target, such as a receptor (biochemistry), receptor, kinase or phosphatase, which in turn mediate the effects of these ...

; the exact role of PEth as a competitive lipid ligand has not been studied extensively.

Marker in blood

Levels of phosphatidylethanols in blood are used as markers of previous alcohol consumption. An increase of alcohol intake by ~20 g ethanol/day will raise the PEth 16:0/18:1 concentration by ~0.10 μmol/L, and vice versa if the alcohol consumption has decreased. However, it has been demonstrated that there can be significant inter-personal variation, leading to potential misclassification between moderate and heavy drinkers. After cessation of alcohol intake, the half-life of PEth is between 4.5 and 10 days in the first week and between 5 and 12 days in the second week. As a blood marker PEth is more sensitive than

carbohydrate deficient transferrin Carbohydrate-deficient transferrin (CDT, also known as desialotransferrin or asialotransferrin) is a laboratory test used to help detect heavy ethanol consumption. Physiology Test for alcohol consumption Carbohydrate-deficient transferrin is el ...

(CDT), urinary

ethyl glucuronide Ethyl glucuronide (EtG) is a metabolite of ethanol which is formed in the body by glucuronidation following exposure to ethanol, usually from drinking alcoholic beverages. It is used as a biomarker to test for ethanol use and to monitor alcohol ...

(EtG) and

ethyl sulfate Ethyl sulfate (IUPAC name: ethyl hydrogen sulfate), also known as sulfovinic acid, is an organic chemical compound used as an intermediate in the production of ethanol from ethylene. It is the ethyl ester of sulfuric acid. History This substanc ...

(EtS).

Interpretation

The Society of PEth Research published a harmonization document (2022 Consensus of Basel) for the interpretation of phosphatidylethanol concentrations in the clinical and forensic setting. This consensus represents the first internationally established harmonization document on PEth. The consensus defined the target measurand (PEth 16:0/18:1 in whole blood), cutoff concentrations (20 ng/mL and 200 ng/mL), and minimal requirements for the applied analytical method (

accuracy and precision Accuracy and precision are two measures of ''observational error''. ''Accuracy'' is how close a given set of measurements (observations or readings) are to their ''true value''. ''Precision'' is how close the measurements are to each other. The ...

within 15%).

References

Phospholipids Ethyl esters {{biochemistry-stub