Phosphatidylethanols (PEth) are a group of phospholipids formed only in the presence of ethanol via the action of phospholipase D (PLD). [1] It accumulates in blood and is removed slowly, making it a useful biomarker for alcohol consumption. [2] PEth is also thought to contribute to the symptoms of alcohol intoxication. [3]
Chemically, phosphatidylethanols are phospholipids carrying two fatty acid chains, which are variable in structure, and one phosphate ethyl ester.
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. [4] 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. [3]
The lipid accumulates in the human body and competes at agonists sites of lipid-gated ion channels contributing to alcohol intoxication. [3] The chemical similarity of PEth to phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2) suggest a likely broad perturbation to lipid signaling; the exact role of PEth as a competitive lipid ligand has not been studied extensively.
Levels of phosphatidylethanols in blood are used as markers of previous alcohol consumption. [5] [6] 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. [7] 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. [2] As a blood marker PEth is more sensitive than carbohydrate deficient transferrin (CDT), urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS). [8]
The Society of PEth Research [9] published a harmonization document (2022 Consensus of Basel) for the interpretation of phosphatidylethanol concentrations in the clinical and forensic setting. [10] This consensus represents the first internationally established harmonization document on PEth and was created by an assembly of the world's leading experts in phosphatidylethanol research. The consensus defines 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 within 15%).
Alcohol intoxication, also known in overdose as alcohol poisoning, commonly described as drunkenness or inebriation, is the behavior and physical effects caused by a recent consumption of alcohol. In addition to the toxicity of ethanol, the main psychoactive component of alcoholic beverages, other physiological symptoms may arise from the activity of acetaldehyde, a metabolite of alcohol. These effects may not arise until hours after ingestion and may contribute to the condition colloquially known as a hangover. The term intoxication is commonly used when large amount of alcohol is consumed along with physical symptoms and deleterious health effects.
Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found in eukaryotes, and was found to be a signaling molecule.
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 acids. They constitute about 0.25% of phospholipids in the bilayer.
Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes in eukaryotic cells. They are a type of lipid, of which its composition affects membrane structure and properties. Two major classes are known: those for bacteria and eukaryotes and a separate family for archaea.
Alcohol and cancer have a complex relationship. Alcohol causes cancers of the oesophagus, liver, breast, colon, oral cavity, rectum, pharynx, and larynx, and probably causes cancers of the pancreas. Cancer risk, can occur even with light to moderate drinking. The more alcohol is consumed, the higher the cancer risk, and no amount can be considered completely safe. Alcoholic beverages were classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC) in 1988. An estimated 3.6% of all cancer cases and 3.5% of cancer deaths worldwide are attributable to consumption of alcohol. 740,000 cases of cancer in 2020 or 4.1% of new cancer cases were attributed to alcohol.
Alcohol tolerance refers to the bodily responses to the functional effects of ethanol in alcoholic beverages. This includes direct tolerance, speed of recovery from insobriety and resistance to the development of alcohol use disorder.
Phospholipase D (EC 3.1.4.4, lipophosphodiesterase II, lecithinase D, choline phosphatase, PLD; systematic name phosphatidylcholine phosphatidohydrolase) is an enzyme of the phospholipase superfamily that catalyses the following reaction
Carbohydrate-deficient transferrin is a laboratory test used to help detect heavy ethanol consumption.
A hangover is the experience of various unpleasant physiological and psychological effects usually following the consumption of alcohol, such as wine, beer, and liquor. Hangovers can last for several hours or for more than 24 hours. Typical symptoms of a hangover may include headache, drowsiness, concentration problems, dry mouth, dizziness, fatigue, gastrointestinal distress, absence of hunger, light sensitivity, depression, sweating, hyper-excitability, irritability, and anxiety.
Fatty acid esters (FAEs) are a type of ester that result from the combination of a fatty acid with an alcohol. When the alcohol component is glycerol, the fatty acid esters produced can be monoglycerides, diglycerides, or triglycerides. Dietary fats are chemically triglycerides.
The enzyme phosphatidate phosphatase (PAP, EC 3.1.3.4) is a key regulatory enzyme in lipid metabolism, catalyzing the conversion of phosphatidate to diacylglycerol:
The short-term effects of alcohol consumption range from a decrease in anxiety and motor skills and euphoria at lower doses to intoxication (drunkenness), to stupor, unconsciousness, anterograde amnesia, and central nervous system depression at higher doses. Cell membranes are highly permeable to alcohol, so once it is in the bloodstream, it can diffuse into nearly every cell in the body.
N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) is an enzyme that catalyzes the release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE). This is a major part of the process that converts ordinary lipids into chemical signals like anandamide and oleoylethanolamine. In humans, the NAPE-PLD protein is encoded by the NAPEPLD gene.
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 abstinence in situations where drinking is prohibited, such as by the military, in alcohol treatment programs, in professional monitoring programs, in schools, liver transplant clinics, or in recovering alcoholic patients. In addition to its use to monitor abstinence and detect drinking, EtG also has potential for monitoring the amount of alcohol use over time because it can be detected in hair and nails, though the effectiveness of this has not yet been proven.
The long-term impact of alcohol on the brain have become a growing area of research focus. While researchers have found that moderate alcohol consumption in older adults is associated with better cognition and well-being than abstinence, excessive alcohol consumption is associated with widespread and significant brain lesions. Other data – including investigated brain-scans of 36,678 UK Biobank participants – suggest that even "light" or "moderate" consumption of alcohol by itself harms the brain, such as by reducing brain grey matter volume. This may imply that alternatives and generally aiming for lowest possible consumption could usually be the advisable approach.
Alcohol, sometimes referred to by the chemical name ethanol, is a depressant drug found in fermented beverages such as beer, wine, and distilled spirit — in particular, rectified spirit. Ethanol is colloquially referred to as "alcohol" because it is the most prevalent alcohol in alcoholic beverages, but technically all alcoholic beverages contain several types of psychoactive alcohols, that are categorized as primary, secondary, or tertiary; Primary, and secondary alcohols, are oxidized to aldehydes, and ketones, respectively, while tertiary alcohols are generally resistant to oxidation; Ethanol is a primary alcohol that has unpleasant actions in the body, many of which are mediated by its toxic metabolite acetaldehyde. Less prevalent alcohols found in alcoholic beverages, are secondary, and tertiary alcohols. For example, the tertiary alcohol 2M2B which is up to 50 times more potent than ethanol and found in trace quantities in alcoholic beverages, has been synthesized and used as a designer drug. Alcoholic beverages are sometimes laced with toxic alcohols, such as methanol and isopropyl alcohol. A mild, brief exposure to isopropyl alcohol is unlikely to cause any serious harm, but many methanol poisoning incidents have occurred through history, since methanol is lethal even in small quantities, as little as 10–15 milliliters. Ethanol is used to treat methanol and ethylene glycol toxicity.
Alcohol intolerance is due to a genetic polymorphism of the aldehyde dehydrogenase enzyme, which is responsible for the metabolism of acetaldehyde. This polymorphism is most often reported in patients of East Asian descent. Alcohol intolerance may also be an associated side effect of certain drugs such as disulfiram, metronidazole, or nilutamide. Skin flushing and nasal congestion are the most common symptoms of intolerance after alcohol ingestion. It may also be characterized as intolerance causing hangover symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or chronic fatigue syndrome. Severe pain after drinking alcohol may indicate a more serious underlying condition.
N-Acetyltaurine (NAcT) is an endogenous metabolite. Biochemically, N-acetyltaurine is formed as a result of an acetylation of taurine. The main substrate for this reaction is acetate. An increase of endogenous N-acetyltaurine concentrations was observed after the consumption of alcohol and after extended physical activity (ketoacidosis).
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 inner leaflet of the plasma membrane with properties of a classic ligand. Other classes of lipid-gated channels include the mechanosensitive ion channels that respond to lipid tension, thickness, and hydrophobic mismatch. A lipid ligand differs from a lipid cofactor in that a ligand derives its function by dissociating from the channel while a cofactor typically derives its function by remaining bound.
Ro 19-4603 is an inverse agonist of the benzodiazepine binding site. It has effects antagonistic to those of benzodiazepines.
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