Chronic alcohol binging injures the liver and other organs by reducing NAD(+) levels required for sirtuin's deacetylase activity

Experimental and Molecular Pathology
Samuel W French

Abstract

NAD(+) levels are markedly reduced when blood alcohol levels are high during binge drinking. This causes liver injury to occur because the enzymes that require NAD(+) as a cofactor such as the sirtuin de-acetylases cannot de-acetylate acetylated proteins such as acetylated histones. This prevents the epigenetic changes that regulate metabolic processes and which prevent organ injury such as fatty liver in response to alcohol abuse. Hyper acetylation of numerous regulatory proteins develops. Systemic multi-organ injury occurs when NAD(+) is reduced. For instance the Circadian clock is altered if NAD(+) is not available. Cell cycle arrest occurs due to up regulation of cell cycle inhibitors leading to DNA damage, mutations, apoptosis and tumorigenesis. NAD(+) is linked to aging in the regulation of telomere stability. NAD(+) is required for mitochondrial renewal. Alcohol dehydrogenase is present in every visceral organ in the body so that there is a systemic reduction of NAD(+) levels in all of these organs during binge drinking.

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Citations

Nov 2, 2019·Nature Reviews. Gastroenterology & Hepatology·Letizia SatrianoJesper B Andersen
Oct 12, 2018·Cellular and Molecular Life Sciences : CMLS·Giuliana Di RoccoGabriele Toietta
Jan 3, 2021·Cell Calcium·Béatrice MorioJennifer Rieusset
Dec 1, 2019·Liver Research·Ryan J Schulze, Wen-Xing Ding
Mar 23, 2021·Gastroenterology Report·Daniel G TenenJustin L Tan
Feb 28, 2018·Trends in Pharmacological Sciences·Eduardo N ChiniWim van Schooten

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