Alcohol Metabolizing Enzymes, Microsomal Ethanol Oxidizing System, Cytochrome P450 2E1, Catalase, and Aldehyde Dehydrogenase in Alcohol-Associated Liver Disease

Abstract

Once ingested, most of the alcohol is metabolized in the liver by alcohol dehydrogenase to acetaldehyde. Two additional pathways of acetaldehyde generation are by microsomal ethanol oxidizing system (cytochrome P450 2E1) and catalase. Acetaldehyde can form adducts which can interfere with cellular function, leading to alcohol-induced liver injury. The variants of alcohol metabolizing genes encode enzymes with varied kinetic properties and result in the different rate of alcohol elimination and acetaldehyde generation. Allelic variants of these genes with higher enzymatic activity are believed to be able to modify susceptibility to alcohol-induced liver injury; however, the human studies on the association of these variants and alcohol-associated liver disease are inconclusive. In addition to acetaldehyde, the shift in the redox state during alcohol elimination may also link to other pathways resulting in activation of downstream signaling leading to liver injury.

Dipeptide YA is Responsible for the Positive Effect of Oyster Hydrolysates on Alcohol Metabolism in Single Ethanol Binge Rodent Models

“…In the liver tissue isolated from the EtOH + saline group, catalase activity was decreased compared to vehicle group, whereas OH combination (EtOH + OH group) significantly decreased EtOH-induced reduction of catalase activity (n = 10, p < 0.05, Figure 5 A). When CYP2E1 uses oxygen for alcohol metabolism, ROS are generated, causing oxidative stress and tissue damage [ 6 ]. In the liver tissue isolated from the EtOH + saline group, CYP2E1 mRNA expression level was highly increased, while OH and HDD combination groups showed lower CYP2E1 expression than the EtOH group ( Figure 5 B).…”

“…Alcohol is metabolized to acetaldehyde by alcohol dehydrogenase (ADH), catalase, and cytochrome P450E1 (CYP2E1). Acetaldehyde is then converted by aldehyde dehydrogenase (ALDH) into acetate [ 6 ]. The causes of these hangover symptoms are known to be toxicity of alcohol and alcohol metabolites, production of free radicals, changes in neurotransmitters and immune factors, and increased inflammatory mediators.…”

The Protective Effects of Water Extracts of Compound Turmeric Recipe on Acute Alcoholism: An Experimental Research Using a Mouse Model

“…The microsomal ethanol oxidation system (MEOS) in hepatocytes requires the participation of cytochrome P450 (CYP450) and nicotinamide adenine dinucleotide phosphoric acid (NADPH) to metabolize ethanol to acetaldehyde. Alcoholism increases the amount of acetaldehyde and consumes more liver P450 enzymes, resulting in insufficient supply of P450 enzymes in the body, and the liver's ability to metabolize alcohol is reduced, resulting in the damage of liver cells by alcohol [ 30 , 31 ]. Therefore, the metabolism of MEOS can be reflected indirectly by observing the activity of P450.…”

Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy

“…Alcohol is a direct hepatotoxin, and its ingestion causes the initiation of numerous metabolic responses that influence the final hepatotoxic response [ 50 , 51 ]. The initial explanation of malnutrition as the major pathogenic mechanism has now given way to the present concept that the alcohol metabolised by the hepatocyte initiates a pathogenic process that involves production of protein-aldehyde adducts, immunologic activity, peroxidation of lipid, and release of cytokines [ 52 ]. Fig.…”