Cytochrome P-4502E1: its physiological and pathological role
Abstract
The role of the microsomal ethanol-oxidizing system (MEOS) in hepatic ethanol metabolism is reviewed, with focus on its constitutive, ethanol-inducible cytochrome P-4502E1 (2E1). The MEOS was purified and reconstituted using 2E1, phospholipids, and cytochrome P-450 reductase and shown to oxidize ethanol to acetaldehyde, mainly as a monooxygenase and secondarily via hydroxyl radicals, with transcriptional and posttranscriptional regulation. Polymorphism of 2E1 was recognized, and enzymology (including cofactors, role of lipids, inducers, and inhibitors) as well as cellular and tissue distribution were chartered. Physiological functions involve lipid metabolism and ketone utilization in starvation, obesity, and diabetes. The most significant role of 2E1 is its adaptive response to high blood ethanol levels with a corresponding acceleration of ethanol metabolism. The associated free radical production, however, contributes to liver injury in the alcoholic. Most importantly, 2E1 has a unique capacity to activate many xenobiotics (85 of which are listed) to hepatotoxic or carcinogenic products. Induction of 2E1 also results in enhanced production of acetaldehyde, a highly reactive and toxic metabolite. The proliferation of the endoplasmic reticulum associated with 2E1 induction is also accompanied by enhanced activity of other cytochrome P-450s, resulting in accelerated metabolism of, and tolerance to, other drugs, as well as increased degradation of retinol and its hepatic depletion. Some substrates and metabolites, however, are innocuous and may eventually be used as markers of heavy drinking. Recently discovered effective 2E1 inhibitors also have great therapeutic potential.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
RNA-seq and qPCR identified a decrease in characteristic hepatocyte-enriched genes with roles in metabolism, regeneration and MASLD/ALD, such as Cyp1a2, Cyp2e1, Ang, Gulo, Hsd3b5, Avpr1a and Chrna4, and an increase in Cyp2f2 in HSC-depleted livers.
“Using RNA sequencing (RNA-seq) and quantitative PCR (qPCR), we identified a decrease in characteristic hepatocyte-enriched genes with roles in metabolism, regeneration and the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD), such as cytochrome P450 oxidases Cyp1a2 and Cyp2e1, and Ang, Gulo, Hsd3b5, Avpr1a and Chrna426–28 as we”
From Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 (2025) · cites this paper as [26]
Cited by
Sorted by citations
Zanger, U. M., & Schwab, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.12.007 · Cited by 4,169 · see citing works
Cederbaum, A. I. (2012) · Clinics in Liver Disease · doi:10.1016/j.cld.2012.08.002 · Cited by 1,145 · see citing works
EASL Clinical Practical Guidelines: Management of Alcoholic Liver Disease
European Association for the Study of the Liver (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.04.004 · Cited by 720 · see citing works
ARAYA, J., RODRIGO, R., VIDELA, L. A., THIELEMANN, L., ORELLANA, M., PETTINELLI, P., & PONIACHIK, J. (2004) · Clinical Science · doi:10.1042/cs20030326 · Cited by 700 · see citing works
Pathogenesis of alcoholic liver disease: Role of oxidative metabolism
Ceni, E., Mello, T., & Galli, A. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i47.17756 · Cited by 521 · see citing works
Lipid accumulation in non-adipose tissue and lipotoxicity
van Herpen, N. A., & Schrauwen-Hinderling, V. B. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.11.049 · Cited by 500 · see citing works
Lieber, C. S. (2005) · Clinics in Liver Disease · doi:10.1016/j.cld.2004.10.005 · Cited by 274 · see citing works
Self-citationCYP induction-mediated drug interactions: in vitro assessment and clinical implications
Lin, J. H. (2006) · Pharmaceutical Research · doi:10.1007/s11095-006-0277-7 · Cited by 264 · see citing works
Alcoholic liver disease: New insights in pathogenesis lead to new treatments
Lieber, C. S. (2000) · Journal of Hepatology · doi:10.1016/s0168-8278(00)80420-1 · Cited by 260 · see citing works
Self-citationCYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis, and apoptosis
Abdelmegeed, M. A., Banerjee, A., Jang, S., Yoo, S.-H., Yun, J.-W., Gonzalez, F. J., Keshavarzian, A., & Song, B.-J. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.09.009 · Cited by 191 · see citing works
Pathogenesis of alcohol‐induced liver disease: Classical concepts and recent advances
Seth, D., Haber, P. S., Syn, W., Diehl, A. M., & Day, C. P. (2011) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2011.06756.x · Cited by 166 · see citing works
Upadhya, S. C., Tirumalai, P. S., Boyd, M. R., Mori, T., & Ravindranath, V. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1477 · Cited by 132 · see citing works
Hepatic stellate cells control liver zonation, size and functions via R-spondin 3
Sugimoto, A., Saito, Y., Wang, G., Sun, Q., Yin, C., Lee, K. H., Geng, Y., Rajbhandari, P., Hernandez, C., Steffani, M., et al. (2025) · Nature · doi:10.1038/s41586-025-08677-w · Cited by 110 · see citing works
Kim, B., Hood, B. L., Aragon, R. A., Hardwick, J. P., Conrads, T. P., Veenstra, T. D., & Song, B. J. (2006) · PROTEOMICS · doi:10.1002/pmic.200500447 · Cited by 83 · see citing works
Abdelmegeed, M. A., Moon, K.-H., Chen, C., Gonzalez, F. J., & Song, B.-J. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.07.016 · Cited by 81 · see citing works
Suh, S., Hood, B. L., Kim, B., Conrads, T. P., Veenstra, T. D., & Song, B. J. (2004) · PROTEOMICS · doi:10.1002/pmic.200400971 · Cited by 76 · see citing works
Intestinal CYP2E1: A mediator of alcohol-induced gut leakiness
Forsyth, C. B., Voigt, R. M., & Keshavarzian, A. (2014) · Redox Biology · doi:10.1016/j.redox.2014.10.002 · Cited by 76 · see citing works
Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function
Lieber, C. S., Leo, M. A., Wang, X., & DeCarli, L. M. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.06.006 · Cited by 71 · see citing works
Self-citationExpression of constitutive and inducible cytochrome P450 2E1 in rat brain
Yadav, S., Dhawan, A., Singh, R. L., Seth, P. K., & Parmar, D. (2006) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-9109-z · Cited by 45 · see citing works
Wang, X., Wu, D., Yang, L., & Cederbaum, A. I. (2011) · Hepatology · doi:10.1002/hep.24540 · Cited by 19 · see citing works
- Authors
- Lieber, C. S.
- Affiliations
- Veterans Health Administration (US)
- Corresponding author
- Lieber, C. S.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 1997-04-01
- Volume
- 77
- Issue
- 2
- Pages
- 517-544
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2124345456
- Cited by
- 889
- References
- 0
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 9 · 2023: 10 · 2022: 16 · 2021: 23 · 2020: 18 · 2019: 22 · 2018: 29 · 2017: 16 · 2016: 27 · 2015: 28 · 2014: 44 · 2013: 39 · 2012: 55
- FWCI
- 29.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01aa005934-14, 5p50aa003508-18)
- National Institute on Alcohol Abuse and Alcoholism (T32AA007275, AA-03508, AA 05934, AA 07275)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- microsomal ethanol oxidizing system, acetaldehyde, enzyme polymorphism, xenobiotic activation, hepatotoxicity, free radicals, endoplasmic reticulum, drug metabolism, alcohol biomarkers, diabetes mellitus, starvation
- MeSH terms
- Ethanol, Animals, Humans, Microsomes, Oxidation-Reduction, Tissue Distribution, Cytochrome P-450 CYP2E1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
