The purpose of these studies was to determine if CYP2E1-mediated alcohol metabolism is required for alcohol-induced microtubule acetylation and associated defects in microtubule-dependent protein trafficking in fully differentiated, polarized, hepatic WIF-B cells (34). CYP2E1 can also carry out the metabolism of arachidonic acid, resulting in the production of several hydroxyeicosatetraenoic acids, some of which may have physiological and pharmacological properties. This chapter focuses on the discussion of CYP2E1 in ethanol metabolism in the CNS, covering topics including how it is regulated, where it is expressed and how it influences sensitivity to ethanol in the brain. Over 90% of consumed alcohol is metabolized through the oxidative pathways that are mediated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) (Lieber, 2005).In this predominant oxidative pathway, alcohol is first oxidized to aldehyde by ADH, followed by ALDH-mediated aldehyde metabolism to acetate. 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. Each enzyme generates acetaldehyde, a toxic and mutagenic metabolite of ethanol. 1996) or via free fatty acid metabolism. In one study, the presence of the rare c2 allele was associated with higher alcohol metabolism in Japanese alcoholics but this effect was only seen at high blood alcohol concentrations. Other enzymes may also assist with the metabolism of alcohol, such as CYP2E1 and catalase, but this is beyond the scope of this article. f2-gnl-11-173: Hepatic metabolism of ethanol by enzymes ADH, CYP2E1 and catalase. Tells how alcohol is broken down and converted into acetaldehyde by liver enzymes and other enzymes in the body, as well as how acetaldehyde is converted into an acetic acid radical. ADH, present in the cytosol, converts ethanol to acetaldehyde. Abstract. CYP2E1 is inducible by ethanol and other low molecular weight substrates(5, 12). 1995a and 1995b, French et al. CYP2E1 may alter the lipid composition of the liver through free radical attack (Nordmann et al. Cytochrome P450 2E1 (CYP2E1) is one of two major enzymes that catalyze ethanol oxidation in the liver. This reaction involves an intermediate carrier of electrons, nicotinamide adenine dinucleotide (NAD+), which is reduced by two electrons to form NADH. The role of CYP2E1 in alcohol metabolism and sensitivity in the central nervous system. It metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including various anaesthetics, paracetamol, benzene, carbon tetrachloride, ethylene glycol, and nitrosamines … CYP2E1 encodes a member of the cytochrome P450 superfamily of enzymes involved in drug metabolism.CYP2E1 is induced by ethanol, the diabetic state, and starvation. Also describes factors which can affect alcohol metabolism including sex, age, genetic make-up, and drink composition. GeneCards - The Human Gene Compendium 1993), by a protein adduct neoantigen autoimmune mechanism (Albano et al. CYP2E1, a gene known for its involvement with ethanol metabolism, maps to this region. Cyp2e1 affects metabolism of toxic-level alcohol, producing ROS as a byproduct. A family‐based genome‐wide linkage analysis using sibling pairs that underwent an alcohol challenge where the level of response to alcohol was measured with the Subjective High Assessment Scale (SHAS) implicated the 10q terminal (10qter) region. Due to polymorphism in the gene whose product enzymes are responsible for alcohol metabolism, serious health consequences including liver cirrhosis and hepatocarcinoma can … Figure 22: The UB3LYP/LACVP** energy profile determined by SCRF calculations for ethanol oxidation in the active site of CYP2E1 through the R-DHA mechanism. 7-9 . Here we explore the effects of CYP2E1 on ATP generated during alcohol metabolism varies as the route of alcohol metabolism Through cytosolic ADH and mitochondrial ALDH 1 cytosolic NADH+ 1 mt NADH= 5ATP Activation of acetate to acetyl-co- enzyme A requires 2 ATP Oxidation Acetyl –co-A in TCA cycle and ETS =10 ATP However net ATP gained is 13 Through CYP2E1 of Endoplasmic reticulum 1st step oxidation from alcohol … CYP2E1 is widely accepted as the sole form of cytochrome P450 responsible for alcohol-mediated increases in acetaminophen (APAP) hepatotoxicity. The energies shown depict the gas phase (no parentheses), the weak-polar medium (parentheses), and the polar medium (brackets). Osna NA, Donohue TM. We therefore blocked de novo methylation of DNA, which we had previously documented to alter Cyp2e1 expression [ 2 ]. Subcell Biochem, 67:177-197, 01 Jan 2013 Cited by: 4 articles | PMID: 23400922. 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