Alcohol consumption causes liver diseases, designated as Alcoholic Liver Disease (ALD). Because
alcohol is detoxified by alcohol dehydrogenase (ADH), a major ethanol metabolism system, the development of
ALD was initially believed to be due to malnutrition caused by alcohol metabolism in liver. The discovery of the
microsomal ethanol oxidizing system (MEOS) changed this dogma. Cytochrome P450 enzymes (CYP) constitute
the major components of MEOS. Cytochrome P450 2E1 (CYP2E1) in MEOS is one of the major ROS generators
in liver and is considered to be contributive to ALD. Our labs have been studying the relationship between
CYP2E1 and ALD for many years. Recently, we found that human CYP2A6 and its mouse analog CYP2A5 are
also induced by alcohol. In mice, the alcohol induction of CYP2A5 is CYP2E1-dependent. Unlike CYP2E1,
CYP2A5 protects against the development of ALD. The relationship of CYP2E1, CYP2A5, and ALD is a major
focus of this review.
Keywords: Alcohol induction, antioxidants, CYP2A5, CYP2A6, CYP2E1, Nrf2, reactive oxygen species, interactions, pyrazole, alcoholic
liver disease, liver fibrosis, nicotine, PPARα, FGF21, LPS, TNFα, MAPK, HIF-1α, autophagy, coumarin 7-hydroxylase.
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