How does alcohol affect the cytochrome P450?
Ethanol is known to induce certain cytochrome P450 (CYP) enzymes, particularly the 2E1 isoform, which has been shown to metabolise arachidonic acid (AA) to the 19-hydroxy metabolite (19-HETE), which could have pro-hypertensive activity; CYP4A, by comparison, is the principal AA omega-hydroxylase in the liver.
Is alcohol dehydrogenase a cytochrome P450?
The enzymes alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1), and catalase all contribute to oxidative metabolism of alcohol. ADH, present in the fluid of the cell (i.e., cytosol), converts alcohol (i.e., ethanol) to acetaldehyde.
Where is CYP2E1 found?
the liver
CYP2E1 is mainly found in the liver but significant amounts are also found in most organs, including the brain (60). CYP2E1 is expressed mainly in the hepatocytes of the liver, however, significant amounts are also found in the Kupffer cells (61), and hepatocyte and Kupffer cell CYP2E1 are inducible e.g. by ethanol.
How does alcohol affect pharmacokinetics?
Alcohol can affect the pharmacokinetics of drugs by altering gastric emptying or liver metabolism (by inducing cytochrome P450 2E1). Drugs may affect the pharmacokinetics of alcohol by altering gastric emptying and inhibiting gastric alcohol dehydrogenase.
Does ethanol inhibit P450?
The role of P450 2E1 in cancer is complex in that P450 2E1 is also induced by ethanol, P450 2E1 is involved in the bioactivation and detoxication of a number of chemical carcinogens, and ethanol is an inhibitor of P450 2E1.
Is alcohol an inducer or inhibitor?
Alcohol is a substrate of CYP2E1, and depending on the frequency of alcohol intake, it can also be either an inducer or inhibitor of CYP2E1.
What is the mechanism of alcohol dehydrogenase?
The alcohol dehydrogenase enzyme is a zinc based enzyme, and the reaction has two steps: Hydrogen is removed from the oxygen on the alcohol. A carbon-oxygen double bond is formed, making the aldehyde, and hydrogen from the carbon is added to NAD to form NADH.
What does alcohol dehydrogenase produce?
Alcohol dehydrogenases are a class of zinc enzymes which catalyse the oxidation of primary and secondary alcohols to the corresponding aldehyde or ketone by the transfer of a hydride anion to NAD+ with release of a proton.
What drugs are metabolized by CYP2E1?
CYP2E1 is an enzyme that particularly participates in the metabolism of endogenous substrates, including acetone and fatty acids (abundant in the brain) [26] and exogenous compounds such as anesthetics, ethanol, nicotine, acetaminophen, acetone, aspartame, chloroform, chlorzoxazone, tetrachloride, and some …
Is CYP2E1 an alcohol dehydrogenase?
The liver metabolizes alcohol using alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1). Both enzymes metabolize ethanol into acetaldehyde, but CYP2E1 activity also results in the production of reactive oxygen species (ROS) that promote oxidative stress.