Interaction between fatty acid oxidation and ethanol metabolism in liver

• Published in: American Journal of Physiology-Gastrointestinal and Liver Physiology Vol. 326; no. 5; pp. G483 - G494
• Main Authors: Lu, Yongke, George, Joseph
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.05.2024
• Subjects: Alcohol; Alcohol dehydrogenase; Catalase; Cytochrome P-450 CYP2E1; Cytochrome P450; Dehydrogenation; Ethanol; Fatty Acids; Fatty Liver; Humans; Hydrogen Peroxide; Liver; Liver diseases; Liver Diseases, Alcoholic; Metabolism; NAD; NADH; Oxidation; Reactive oxygen species; Review; Steatosis; NAD; peroxisomes; CYP2E1; catalase; hydrogen peroxide
• ISSN: 0193-1857; 1522-1547; 1522-1547
• DOI: 10.1152/ajpgi.00281.2023

Fatty acid oxidation (FAO) releases the energy stored in fat to maintain basic biological processes. Dehydrogenation is a major way to oxidize fatty acids, which needs NAD + to accept the released H + from fatty acids and form NADH, which increases the ratio of NADH/NAD + and consequently inhibits FAO leading to the deposition of fat in the liver, which is termed fatty liver or steatosis. Consumption of alcohol (ethanol) initiates simple steatosis that progresses to alcoholic steatohepatitis, which constitutes a spectrum of liver disorders called alcohol-associated liver disease (ALD). ALD is linked to ethanol metabolism. Ethanol is metabolized by alcohol dehydrogenase (ADH), microsomal ethanol oxidation system (MEOS), mainly cytochrome P450 2E1 (CYP2E1), and catalase. ADH also requires NAD + to accept the released H + from ethanol. Thus, ethanol metabolism by ADH leads to increased ratio of NADH/NAD + , which inhibits FAO and induces steatosis. CYP2E1 directly consumes reducing equivalent NADPH to oxidize ethanol, which generates reactive oxygen species (ROS) that lead to cellular injury. Catalase is mainly present in peroxisomes, where very long-chain fatty acids and branched-chain fatty acids are oxidized, and the resultant short-chain fatty acids will be further oxidized in mitochondria. Peroxisomal FAO generates hydrogen peroxide (H 2 O 2 ), which is locally decomposed by catalase. When ethanol is present, catalase uses H 2 O 2 to oxidize ethanol. In this review, we introduce FAO (including α-, β-, and ω-oxidation) and ethanol metabolism (by ADH, CYP2E1, and catalase) followed by the interaction between FAO and ethanol metabolism in the liver and its pathophysiological significance.