Enzymatic Mechanisms of Ethanol Oxidation in the Brain
Abstract
Background: The exact enzymatic mechanisms of ethanol oxidation in the brain are still unclear. The catalase‐mediated oxidation of ethanol was demonstrated in rat brain using incubation of brain homogenates with catalase inhibitors. The role of the alcohol dehydrogenase (ADH) or cytochrome P450–dependent system in this process is possible, but has not been confirmed. The objective of the study was to determine the contribution of the different enzymatic pathways to ethanol oxidation in brain homogenates from mice and rats. Methods: Three approaches were used to investigate the enzymatic mechanisms of ethanol oxidation in the brain of rats and mice: (1) preincubation of brain homogenates with inhibitors of the ethanol‐metabolizing enzymes (catalase, CYP2E1, ADH, and ALDH); (2) utilization of mice with genetic deficiency in ethanol‐metabolizing enzymes (catalase, CYP2E1, or both enzymes); and (3) determination of ethanol oxidation in brain subcellular fractions known to have differential activity of ethanol‐metabolizing enzymes. The ethanol‐derived acetaldehyde (AC) and acetate were determined in brain samples by gas chromatography. Results: The catalase inhibitors sodium azide (5 mM) and aminotriazole (5 mM) as well as CYP2E1 inhibitors diallyl sulfide (2 mM) and β‐phenethyl isothiocyanate (0.1 mM) lowered significantly the accumulation of the ethanol‐derived AC and acetate in brain homogenates. The ADH inhibitor 4‐methyl pyrazole (5 mM) significantly decreased the acetate but not the AC accumulation. Ethanol‐derived AC accumulation in brain homogenates of acatalasemic mice was 47% of the control value, 91% in CYP2E1‐null mice, and 24% in double mutants (with deficiency of both catalase and CYP2E1). The highest levels of ethanol oxidation were found in microsomal and peroxisomal subcellular brain fractions, where CYP2E1 and catalase are located, respectively. Conclusions: Catalase is the key enzyme of ethanol oxidation in the brain of rodents: it may be responsible for about 60% of the process. CYP2E1 plays an important role in ethanol oxidation in the rodent brains. Alcohol dehydrogenase plays a minor role, if any, in this process. Aldehyde dehydrogenase plays the crucial role in the further oxidation of ethanol‐derived AC in the brain homogenates.
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?
Ethanol oxidizing enzymes are functional in the brain and include ADH, catalase, CYP2E1, and ALDH2, which make different contributions.
“Similar to the liver, ethanol oxidizing enzymes are also functional in the brain and include ADH, catalase, CYP2E1, and ALDH2, which make different contributions.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [147]
Cerebral ADH plays very little or virtually no role in ethanol metabolism in the brain compared to its hepatic isoform, whereas cerebral catalase acts as the main oxidizing enzyme, accounting for more than 60% of ethanol oxidation in the brain under normal conditions.
“Cerebral ADH plays very little or virtually no role in ethanol metabolism in the brain compared to its action by its hepatic isoform.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [147]
ALDH1B and other isoforms may be involved in acetaldehyde metabolism in rodents.
“In contrast, ALDH1B and other isoforms may be involved in acetaldehyde metabolism in rodents145,147,163.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [147]
Cites
Dawson, R. M. C. (1987) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(87)90411-7 · Cited by 2,961 · see citing works
Role of CYP2E1 in the Hepatotoxicity of Acetaminophen
Lee, S. S. T., Buters, J., Pineau, T., Fernández‐Salguero, P. M., & Gonzalez, F. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.20.12063 · Cited by 655 · see citing works
Self-citationInhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites
Brady, J. F., Ishizaki, H., Fukuto, J. M., Lin, M. C., Fadel, A., Gapac, J. M., & Yang, C. S. (1991) · Chemical Research in Toxicology · doi:10.1021/tx00024a008 · Cited by 262 · see citing works
Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system
Hansson, T., Tindberg, N., Ingelman-Sundberg, M., & Ko¨hler, C. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90154-v · Cited by 202 · see citing works
Multiple mechanisms in the regulation of ethanol‐inducible cytochrome P450IIE1
Koop, D. R., & Tierney, D. J. (1990) · BioEssays · doi:10.1002/bies.950120906 · Cited by 199 · see citing works
Ethanol metabolism in rat brain homogenates by a catalase-H2O2 system
Aragón, C. M. G., Rogan, F., & Amit, Z. (1992) · Biochemical Pharmacology · doi:10.1016/0006-2952(92)90042-h · Cited by 183 · see citing works
Enzymatic Production of Acetaldehyde from Ethanol in Rat Brain Tissue
Gill, K. J., Menez, J. F., Lucas, D., & Deitrich, R. A. (1992) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1992.tb01892.x · Cited by 163 · see citing works
Self-citationRole of acetaldehyde in the actions of ethanol on the brain — A review
Hunt, W. A. (1996) · Alcohol · doi:10.1016/0741-8329(95)02026-8 · Cited by 162 · 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
Catalase Mediates Acetaldehyde Formation from Ethanol in Fetal and Neonatal Rat Brain
Hamby‐Mason, R., Chen, J. J., Schenker, S., Perez, A., & Henderson, G. I. (1997) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1997.tb04255.x · Cited by 132 · see citing works
Ethanol metabolism in the brain
Zimatkin, S. M., & Deitrich, R. A. (1997) · Addiction Biology · doi:10.1080/13556219772444 · Cited by 125 · see citing works
Self-citationDistribution and Kinetics of Ethanol Metabolism in Rat Brain
Zimatkin, S. M., Liopo, A. V., & Deitrich, R. A. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb03958.x · Cited by 111 · see citing works
Self-citationSELECTIVE INHIBITION OF CYP2B6-CATALYZED BUPROPION HYDROXYLATION IN HUMAN LIVER MICROSOMES IN VITRO
Turpeinen, M., Nieminen, R. M., Juntunen, T., Taavitsainen, P., Raunio, H., & Pelkonen, O. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.32.6.626 · Cited by 108 · see citing works
Histochemical Study of Aldehyde Dehydrogenase in the Rat CNS
Zimatkin, S. M. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb02555.x · Cited by 84 · see citing works
Self-citationIshizaki, H., Brady, J. F., Ning, S. M., & Yang, C. S. (1990) · Xenobiotica · doi:10.3109/00498259009046845 · Cited by 77 · see citing works
SMITH, B. R., Aragón, C. M. G., & Amit, Z. (1997) · Addiction Biology · doi:10.1080/13556219772570 · Cited by 75 · see citing works
Distribution of alcohol dehydrogenase mRNA in the rat central nervous system.
Martínez, S. E., Vaglenova, J., Sabrià, J., Martı́nez, M. C., Farrés, J., & Parés, X. (2001) · European Journal of Biochemistry · doi:10.1046/j.0014-2956.2001.02416.x-i2 · Cited by 67 · see citing works
The Role of Acetaldehyde in the Central Effects of Ethanol
Quertemont, É., Grant, K. A., Correa, M., Arizzi, M. N., Salamone, J. D., Tambour, S., Aragón, C. M. G., McBride, W. J., Rodd, Z. A., D, A. G. M., et al. (2005) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000156185.39073.d2 · Cited by 66 · see citing works
CYP2E1 and catalase influence ethanol sensitivity in the central nervous system
Vasiliou, V., Ziegler, T. L., Bludeau, P., Petersen, D. R., Gonzalez, F. J., & Deitrich, R. A. (2006) · Pharmacogenetics and Genomics · doi:10.1097/01.fpc.0000182777.95555.56 · Cited by 58 · see citing works
Self-citationAcetaldehyde: déjà vu du jour.
Deitrich, R. A. (2004) · Journal of Studies on Alcohol · doi:10.15288/jsa.2004.65.557 · Cited by 52 · see citing works
Self-citationFeinstein, R. N., Seaholm, J. E., Howard, J. B., & Russell, W. L. (1964) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.52.3.661 · Cited by 37 · see citing works
Is Ethanol a Pro-Drug? Acetaldehyde Contribution to Brain Ethanol Effects
Quertemont, É., Eriksson, C. J. P., Zimatkin, S. M., Pronko, P. S., Diana, M., Pisano, M., Rodd, Z. A., Bell, R. L., & Ward, R. J. (2005) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000175015.51329.45 · Cited by 30 · see citing works
Self-citationPerson, R., Chen, H., Fantel, A. G., & Juchau, M. R. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb02114.x · Cited by 27 · see citing works
Lambard, S. E., Burnett, A. K., Wolf, C. R., & Craft, J. A. (1991) · Biochemical Pharmacology · doi:10.1016/0006-2952(91)90421-z · Cited by 18 · see citing works
Azide Inhibits Human Cytochrome P‐4502E1, 1A2, and 3A4
Salmela, K. S., Ib, T., & Lieber, C. S. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2001.tb02206.x · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rungratanawanich, W., Qu, Y., Wang, X., Essa, M. M., & Song, B.-J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00561-7 · Cited by 411 · see citing works
Alcohol metabolism contributes to brain histone acetylation
Mews, P., Egervári, G., Nativio, R., Sidoli, S., Donahue, G., Lombroso, S. I., Alexander, D. C., Riesche, S. L., Heller, E. A., Nestler, E. J., et al. (2019) · Nature · doi:10.1038/s41586-019-1700-7 · Cited by 258 · see citing works
Metabolic Methanol: Molecular Pathways and Physiological Roles
Dorokhov, Y. L., Shindyapina, A. V., Sheshukova, E. V., & Komarova, T. V. (2015) · Physiological Reviews · doi:10.1152/physrev.00034.2014 · Cited by 226 · see citing works
The role of oxidative stress in fetal alcohol spectrum disorders
Brocardo, P. S., Gil‐Mohapel, J., & Christie, B. R. (2011) · Brain Research Reviews · doi:10.1016/j.brainresrev.2011.02.001 · Cited by 185 · see citing works
“Alternatively, ethanol can also be metabolized by the enzyme cytochrome P450 2E1, which is present both in the liver and in the brain (Hansson et al., 1990; Upadhya et al., 2000; Zimatkin et al., 2006) and has been found in human fetal brain cells (Khalighi et al., 1999).”
Jin, M., Ande, A., Kumar, A., & Kumar, S. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.78 · Cited by 181 · see citing works
“peroxidation in the brain, leading to increased permeability of BBB and dysfunction of mitochondria.(10,11) Consistent with these observations, our previous study has shown that ethanol upregulates CYP2E1 in the U937 cell line and its expression is associated with increased oxidative stress.”
BackgroundResultLipids and Oxidative Stress Associated with Ethanol‐Induced Neurological Damage
Hernández-Hernández, J. A., López-Sánchez, R. C., & Rendón-Ramírez, A. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/1543809 · Cited by 161 · see citing works
Griffin, W. C., Lopez, M. F., Yanke, A. B., Middaugh, L. D., & Becker, H. C. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1324-3 · Cited by 136 · see citing works
“Furthermore, although catalase appears to be an important metabolic pathway for ethanol in brain, CYP2E1 also contributes significantly to brain ethanol metabolism (Zimatkin et al. 2006).”
BackgroundEthanol metabolism: The good, the bad, and the ugly
Wilson, D. F., & Matschinsky, F. M. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.109638 · Cited by 134 · see citing works
Brain ethanol metabolism by astrocytic ALDH2 drives the behavioural effects of ethanol intoxication
Jin, S., Cao, Q., Yang, F., Zhu, H., Xu, S., Chen, Q., Wang, Z., Lin, Y., Çınar, R., Pawlosky, R. J., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00357-z · Cited by 121 · see citing works
The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain
García-Suástegui, W. A., Ramos-Chávez, L. A., Rubio‐Osornio, M., Calvillo-Velasco, M., Atzin-Méndez, J. A., Guevara, J., & Silva‐Adaya, D. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/4680732 · Cited by 120 · see citing works
“Inhibitors of ADH decrease the acetate but not the acetaldehyde [139].”
BackgroundImpact of Alcohol Consumption on Male Fertility Potential: A Narrative Review
Finelli, R., Mottola, F., & Agarwal, A. K. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19010328 · Cited by 124 · see citing works
“In the brain, the enzymes, catalase and cytochrome P450 (CYP450), oxidize 65% and 20% of the EtOH into acetaldehyde (Figure 1), respectively [25].”
BackgroundPiecing together the puzzle of acetaldehyde as a neuroactive agent
Correa, M., Salamone, J. D., Segovia, K. N., Pardo, M., Longoni, R., Spina, L., Peana, A. T., Vinci, S., & Acquas, E. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.07.009 · Cited by 118 · see citing works
Effect of alcohol on blood pressure
Tasnim, S., Tang, C., Musini, V. M., & Wright, J. M. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012787.pub2 · Cited by 126 · see citing works
Söderpalm, B., & Ericson, M. (2011) · Current topics in behavioral neurosciences · doi:10.1007/978-3-642-28720-6_170 · Cited by 117 · see citing works
Ethanol as a Prodrug: Brain Metabolism of Ethanol Mediates its Reinforcing Effects
Karahanian, E., Quintanilla, M. E., Tampier, L., Rivera‐Meza, M., Bustamante, D., González-Lira, V., Morales, P., Herrera‐Marschitz, M., & Israel, Y. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01439.x · Cited by 113 · see citing works
“It is estimated that brain catalase accounts for 60-70% of acetaldehyde generated in this organ, while CYP2E1 accounts for 10-20% (Zimatkin et al., 2006; Zimatkin et al., 1998).”
BackgroundPutative Role of Brain Acetaldehyde in Ethanol Addiction
Deng, X.-S., & Deitrich, R. (2008) · Current Drug Abuse Reviewse · doi:10.2174/1874473710801010003 · Cited by 105 · see citing works
“By using catalase inhibitors or inducers, further studies demonstrated that AcH formation can be modified after EtOH addition [9,20-25].”
BackgroundMethodResultInfluentialSelf-citationCytochrome P450 expression and regulation in the brain
Kuban, W., & Daniel, W. A. (2020) · Drug Metabolism Reviews · doi:10.1080/03602532.2020.1858856 · Cited by 104 · see citing works
“CYP2E1 plays an important role in ethanol oxidation in the brain of rodents (Zimatkin et al. 2006).”
BackgroundGonzález, A., Pariente, J. A., & Salido, G. M. (2007) · Brain Research · doi:10.1016/j.brainres.2007.08.040 · Cited by 100 · see citing works
Rao, P., Midde, N. M., Miller, D. D., Chauhan, S. C., Kumar, A., & Kumar, S. (2015) · Current Drug Metabolism · doi:10.2174/1389200216666150812123554 · Cited by 97 · see citing works
“In this study, ethanol pretreated rat or brain homogenates when exposed to 2 mM DAS significantly diminishes alcohol-derived acetaldehyde and acetate formation [107].”
MethodThe Role of CYP2E1 in Alcohol Metabolism and Sensitivity in the Central Nervous System
Heit, C., Dong, H., Chen, Y., Thompson, D. C., Deitrich, R. A., & Vasiliou, V. (2013) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-007-5881-0_8 · Cited by 93 · see citing works
Self-citationAlcohol dehydrogenase and aldehyde dehydrogenase in malignant neoplasms
Orywal, K., & Szmitkowski, M. (2016) · Clinical and Experimental Medicine · doi:10.1007/s10238-016-0408-3 · Cited by 91 · see citing works
“It is found that alcohol metabolism in brain depends mostly on catalase and cytochrome P450 2E1 and only in 20 % on oxidation with alcohol dehydrogenase [67].”
BackgroundRole of acetaldehyde in mediating the pharmacological and behavioral effects of alcohol.
Quertemont, É., & Didone, V. (2006) · PubMed Central · Cited by 87 · see citing works
Fernandes, L. M. P., Bezerra, F. R., Monteiro, M. C., Silva, M. L., de Oliveira, F. R., Lima, R. R., Fontes-Júnior, E. A., & Maia, C. D. S. F. (2017) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2016.267 · Cited by 84 · see citing works
Shaik, N. M., Giri, N., Pan, G., & Elmquist, W. F. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.017723 · Cited by 84 · see citing works
Liang, G., Chen, M., Pan, X., Zheng, J., & Wang, H. (2010) · Experimental and Toxicologic Pathology · doi:10.1016/j.etp.2010.04.015 · Cited by 82 · see citing works
“Moreover, the incidence of prenatal ethanol exposure is on an upward trend throughout recent years (Zimatkin et al., 2006).”
BackgroundEthanol Pharmacokinetics in Neonates and Infants
Marek, E., & Kraft, W. K. (2014) · Current Therapeutic Research · doi:10.1016/j.curtheres.2014.09.002 · Cited by 79 · see citing works
“In rodents, catalase has been proposed to account for 60% of ethanol oxidation in the brain, whereas CYP2E1 may account for 20% of ethanol oxidation in the brain.(43) Animal studies have shown that acetaldehyde adducts are expressed in neonatal brains exposed to ethanol in utero.”
BackgroundZhong, Y., Dong, G., Luo, H., Cao, J., Wang, C., Wu, J., Feng, Y.-Q., & Yue, J. (2012) · Toxicology · doi:10.1016/j.tox.2012.08.009 · Cited by 77 · see citing works
A Comprehensive View of the Neurotoxicity Mechanisms of Cocaine and Ethanol
Pereira, R. B., Andrade, P. B., & Valentão, P. (2015) · Neurotoxicity Research · doi:10.1007/s12640-015-9536-x · Cited by 73 · see citing works
“However, ACH can be formed directly in the brain, to a lesser extent, by the action of catalase and CYP 2E1 (Zimatkin et al. 2006).”
BackgroundGenetics and genomics of alcohol sensitivity
Morozova, T. V., Mackay, T. F. C., & Anholt, R. R. H. (2014) · Molecular Genetics and Genomics · doi:10.1007/s00438-013-0808-y · Cited by 64 · see citing works
“Studies on rat brain homogenates suggest that ethanol metabolism proceeds here via catalase and cytochrome P450 (CYP2e1), which inactivate about 60– 70 % and about 20 % of ethanol, respectively, via oxidation (Zimatkin et al. 2006).”
BackgroundHoward, E. C., Schier, C. J., Wetzel, J., Duvauchelle, C. L., & Gonzales, R. A. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.04.014 · Cited by 64 · see citing works
Endogenous ethanol production in health and disease
Meijnikman, A. S., Nieuwdorp, M., & Schnabl, B. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00937-w · Cited by 69 · see citing works
“In the brain, the oxidation of ethanol is predominantly mediated by CYP2E1, with a negligible contribution from ADH 195,196 .”
Oxidation of ethanol in the brain and its consequences.
Deitrich, R. A., Zimatkin, S. M., & Pronko, S. P. (2006) · PubMed Central · Cited by 63 · see citing works
Self-citationRepeated ethanol exposure alters social behavior and oxidative stress parameters of zebrafish
Müller, T. E., Nunes, S. Z., Silveira, A., Loro, V. L., & Rosemberg, D. B. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.05.026 · Cited by 62 · see citing works
Kim, Y. S., & Kim, S. G. (2020) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2020.0173 · Cited by 62 · see citing works
Acetate Causes Alcohol Hangover Headache in Rats
Maxwell, C. R., Spangenberg, R. J., Hoek, J. B., Silberstein, S. D., & Oshinsky, M. L. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015963 · Cited by 60 · see citing works
“aldehyde dehydrogenase in many tissues, including brain tissue [8,9,10].”
BackgroundLipophagy and Alcohol-Induced Fatty Liver
Li, Y., Yang, C., Thomes, P. G., Kharbanda, K. K., Casey, C. A., McNiven, M. A., & Donohue, T. M. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00495 · Cited by 60 · see citing works
Correa, M., Manrique, H. M., Font, L., Escrig, M. A., & Aragón, C. M. G. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1219-3 · Cited by 59 · see citing works
“The use of drugs like disulfiram or cyanamide, which block acetaldehyde elimination by inhibiting aldehyde dehydrogenase (ALDH), the enzyme that metabolizes acetaldehyde into acetic acid (Zimatkin and Deitrich 1997; Zimatkin et al. 2006), is one of the oldest pharmacological tools to treat alcoholism (Eriksson 2001; N…”
BackgroundInfluentialDNA damage and neurotoxicity of chronic alcohol abuse
Kruman, I. I., Henderson, G. I., & Bergeson, S. E. (2012) · Experimental Biology and Medicine · doi:10.1258/ebm.2012.011421 · Cited by 54 · see citing works
Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders
Bhatia, S., Drake, D. M., Miller, L., & Wells, P. G. (2019) · Birth Defects Research · doi:10.1002/bdr2.1509 · Cited by 57 · see citing works
“Abbreviations: ADH1, alcohol dehydrogenase; ALDH2, aldehyde dehydrogenase; CH3C •HOH, α-hydroxyethyl alcohol; CYP2E1, cytochrome P450 2E1; H2O2, hydrogen peroxide; HO•, hydroxyl radicals; NADPH, nucleotide adenine dinucleotide phosphate; O2 •-, superoxide anions radical formation (Koop, 2006).”
BackgroundInfluentialMystic Acetaldehyde: The Never-Ending Story on Alcoholism
Peana, A. T., Sánchez-Catalán, M. J., Hipólito, L., Rosas, M., Porru, S., Bennardini, F., Romualdi, P., Caputi, F. F., Candeletti, S., Polache, A., et al. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00081 · Cited by 57 · see citing works
“Finally, acetaldehyde oxidation is required for detoxification and it can be metabolized into acetate by ALDH that plays a crucial role in further oxidizing ethanol-derived acetaldehyde (Zimatkin et al., 2006).”
BackgroundInfluentialHipólito, L., Sánchez-Catalán, M. J., Martí‐Prats, L., Granero, L. M., & Polache, A. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.07.007 · Cited by 54 · see citing works
Ethanol oxidation in the living brain
Zimatkin, S. M., & Бубен, А. Л. (2007) · Alcohol and Alcoholism · doi:10.1093/alcalc/agm059 · Cited by 54 · see citing works
“…CYP450 2E1 in ethanol oxidation in the rodent brains has been demonstrated using the specific enzyme inhibitors, mice with genetic deficiency in ethanol-metabolizing enzymes and brain subcellular fractions known to have differential activity of ethanol-metabolizing enzymes (Zimatkin et al ., 2006).”
BackgroundMethodSelf-citationThe inflammatory footprints of alcohol-induced oxidative damage in neurovascular components
Alikunju, S., Muneer, P. M. A., Zhang, Y., Szlachetka, A. M., & Haorah, J. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.01.007 · Cited by 53 · see citing works
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript microvessel endothelium (Haorah et al., 2005b; Martinez et al., 2001; Zimatkin et al., 2006).”
BackgroundCytochrome P450 in the central nervous system as a therapeutic target in neurodegenerative diseases
Navarro‐Mabarak, C., Camacho‐Carranza, R., & Espinosa-Aguirre, J. J. (2018) · Drug Metabolism Reviews · doi:10.1080/03602532.2018.1439502 · Cited by 53 · see citing works
Current View on the Mechanisms of Alcohol-Mediated Toxicity
Birková, A., Hubková, B., Čižmárová, B., & Bolerázska, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189686 · Cited by 52 · see citing works
“Oxidation by CYP2E1 also occurs in the brain, and the alcohol dehydrogenase action is minor, if any [56,57].”
BackgroundMelis, M., Carboni, E., Caboni, P., & Acquas, E. (2013) · Addiction Biology · doi:10.1111/adb.12097 · Cited by 52 · see citing works
“…for the Study of Addiction Addiction Biology, 20, 182–193 Heikkila 1980; Aragon, Spivak & Amit 1991; Aragon, Rogan & Amit 1992; Gill et al. 1992; Zimatkin et al. 2006), whose inhibition prevents a number of ethanolmediated behavioral responses ranging from voluntary consumption (Aragon &…”
BackgroundCui, J., Liu, Y., Chang, X., Gou, W., Zhou, X., Liu, Z., Li, Z., Wu, Y., & Zuo, D. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2593742 · Cited by 49 · see citing works
“ADE has been proved contributing to many adverse effects of alcohol [12].”
BackgroundRetractedImpaired one carbon metabolism and DNA methylation in alcohol toxicity
Kruman, I. I., & Fowler, A. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12677 · Cited by 47 · see citing works
Catalase mediates acetaldehyde formation in the striatum of free-moving rats
Jamal, M., Ameno, K., Uekita, I., Kumihashi, M., Wang, W., & Ijiri, I. (2007) · NeuroToxicology · doi:10.1016/j.neuro.2007.05.002 · Cited by 47 · see citing works
Effects of Beverages on Alcohol Metabolism: Potential Health Benefits and Harmful Impacts
Wang, F., Zhang, Y., Zhou, Y., Li, Y., Zhou, T., Zheng, J., Zhang, J., Li, S., Xu, D.-P., & Li, H. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030354 · Cited by 45 · see citing works
“into acetic acid with catalysis of mitochondrial aldehyde dehydrogenase (ALDH) [8,9].”
MethodThe “First Hit” Toward Alcohol Reinforcement: Role of Ethanol Metabolites
Israel, Y., Quintanilla, M. E., Karahanian, E., Rivera‐Meza, M., & Herrera‐Marschitz, M. (2015) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12709 · Cited by 44 · see citing works
Role of Alcohol Oxidative Metabolism in Its Cardiovascular and Autonomic Effects
El‐Mas, M. M., & Abdel‐Rahman, A. A. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-6260-6_1 · Cited by 44 · see citing works
Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage
Ruiter-Lopez, L., Khan, M. A. S., Wang, X., & Song, B. (2025) · Antioxidants · doi:10.3390/antiox14030302 · Cited by 45 · see citing works
Clarke, R. B. C., Adermark, L., Chau, P., Söderpalm, B., & Ericson, M. (2014) · Alcohol and Alcoholism · doi:10.1093/alcalc/agu047 · Cited by 43 · see citing works
“Pre-treatment with inhibitors of catalase, the major enzyme responsible for converting EtOH into acetaldehyde in the brain (Zimatkin et al., 2006), attenuates EtOH-induced locomotion (Aragon and Amit, 1993; Sanchis-Segura et al.”
BackgroundQuintanilla, M. E., Rivera‐Meza, M., Berríos‐Cárcamo, P., Bustamante, D., Buscaglia, M., Morales, P., Karahanian, E., Herrera‐Marschitz, M., & Israel, Y. (2014) · Alcohol · doi:10.1016/j.alcohol.2014.07.003 · Cited by 43 · see citing works
Mitochondrial Permeability Transition Pore Inhibitors Prevent Ethanol-Induced Neuronal Death in Mice
Lamarche, F., Carcenac, C., Gonthier, B., Cottet‐Rousselle, C., Chauvin, C., Barret, L. G., Leverve, X. M., Savasta, M., & Fontaine, E. M. (2012) · Chemical Research in Toxicology · doi:10.1021/tx300395w · Cited by 43 · see citing works
Ethanol-Induced Cell Damage Can Result in the Development of Oral Tumors
Hoes, L., Dok, R., Verstrepen, K. J., & Nuyts, S. (2021) · Cancers · doi:10.3390/cancers13153846 · Cited by 38 · see citing works
“Catalase is especially important in the brain or in a fasted state [104,112,113].”
BackgroundReward and Relapse: Complete Gene‐Induced Dissociation in an Animal Model of Alcohol Dependence
Quintanilla, M. E., Tampier, L., Karahanian, E., Rivera‐Meza, M., Herrera‐Marschitz, M., & Israel, Y. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01606.x · Cited by 40 · see citing works
“The residual 20% formation is likely due to acetaldehyde generation by CYP2E1 (Zimatkin et al., 2006).”
BackgroundKapur, B. M., Vandenbroucke, A. C., Adamchik, Y., Lehotay, D. C., & Carlen, P. L. (2007) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2007.00541.x · Cited by 39 · see citing works
Ren, J. T., Babcock, S. A., Li, Q., Huff, A. F., Li, S., & Doser, T. A. (2009) · Toxicology Letters · doi:10.1016/j.toxlet.2009.02.019 · Cited by 40 · see citing works
“alcohol or its metabolite acetaldehyde, accumulation of reactive oxygen species and fatty acid ethyl esters, modifications of lipoprotein and apolipoprotein particles, insulin resistance, metabolic and excitotoxic changes as well as genetic predisposition (Hannuksela et al. 2002; Li and Ren 2007a; Zhang et al. 2004; Z…”
BackgroundAlcohol-Induced Epigenetic Changes in Cancer
Dumitrescu, R. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8751-1_9 · Cited by 39 · see citing works
Mocelin, R., Marcon, M., Araújo, A. S. D. R., Herrmann, A. P., & Piato, Â. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.03.014 · Cited by 39 · see citing works
Andresen, H., Schmoldt, H., Matschke, J., Flachskampf, F. A., & Turk, E. E. (2008) · Forensic Science International · doi:10.1016/j.forsciint.2008.05.014 · Cited by 37 · see citing works
“For the metabolism of alcohols in brain, catalase and cytochrome P450 2E1 are more important than alcohol dehydrogenases [28].”
BackgroundToselli, F., Dodd, P. R., & Gillam, E. M. J. (2016) · Drug Metabolism Reviews · doi:10.1080/03602532.2016.1221960 · Cited by 36 · see citing works
“Selective inhibition studies on rat brain microsomes and homogenates provided evidence for in situ CYP2E1mediated alcohol metabolism (Quertemont et al., 2005; Zimatkin et al., 2006).”
BackgroundEscrig, M. A., Pardo, M., Aragón, C. M. G., & Correa, M. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.10.002 · Cited by 35 · see citing works
“…acetaldehyde contributes to the anxiolytic effects of ethanol, since catalase has a minor role in peripheral ethanol metabolism (Hunt, 1996) but seems to have a critical role in brain ethanol metabolism (Aragon et al., 1992; Correa et al., 2009; Zimatkin and Deitrich, 1997; Zimatkin et al., 2006).”
InfluentialTampier, L., Quintanilla, M. E., Karahanian, E., Rivera‐Meza, M., Herrera‐Marschitz, M., & Israel, Y. (2013) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12101 · Cited by 35 · see citing works
“While alcohol dehydrogenase is not expressed in the brain (see Deitrich, 2011; Zimatkin et al., 2006), acetaldehyde can be generated in this organ by the action of catalase on EtOH and to a minor extent by CYP2E1, both enzymes present in the brain (Aragon et al.”
BackgroundKarahanian, E., Rivera‐Meza, M., Tampier, L., Quintanilla, M. E., Herrera‐Marschitz, M., & Israel, Y. (2014) · Addiction Biology · doi:10.1111/adb.12130 · Cited by 35 · see citing works
“It is noted that while alcohol dehydrogenase is not expressed in the brain, several in vitro studies have indicated that acetaldehyde is generated from ethanol by the action of brain catalase (Tampier & Mardones 1979; Aragon, Rogan & Amit 1992; Zimatkin et al. 2006) and, to a minor extent, by CYP2E1 (Zimatkin et al. 2…”
BackgroundInfluentialRecent advances in alcohol metabolism: from the gut to the brain
Goldman, M. R., Molina-Castro, M., Etkins, J. C., Koide, T. L., Ramchandani, V. A., Plawecki, M. H., Mennella, J. A., & Pepino, M. Y. (2025) · Physiological Reviews · doi:10.1152/physrev.00053.2024 · Cited by 34 · see citing works
Rulten, S. L., Hodder, E., Ripley, T. L., Stephens, D. N., & Mayne, L. V. (2008) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2008.00673.x · Cited by 33 · see citing works
Sánchez-Catalán, M. J., Hipólito, L., Guerri, C., Granero, L. M., & Polache, A. (2008) · Alcohol and Alcoholism · doi:10.1093/alcalc/agn012 · Cited by 34 · see citing works
Zhu, Y., Zuo, N., Li, B., Xiong, Y., Chen, H., He, H., Sun, Z., Hu, S., Cheng, H., Ao, Y., et al. (2018) · Toxicology · doi:10.1016/j.tox.2018.03.004 · Cited by 33 · see citing works
Orrico‐Sánchez, A., Hipólito, L., Sánchez-Catalán, M. J., Martí‐Prats, L., Zornoza, T., Granero, L. M., & Polache, A. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3065-1 · Cited by 33 · see citing works
“In this sense, the definitive demonstration that this metabolite can be formed in the brain by enzymatic transformation of ethanol, with the main participation of catalase and CYP2E1 (Aragon et al. 1992; Zimatkin et al. 2006; Hipolito et al. 2007; Sanchez-Catalan et al. 2008), has been crucial when considering its rol…”
Plescia, F., Brancato, A., Vènniro, M., Maniaci, G., Cannizzaro, E., Sutera, F. M., De, V., Giannola, L. I., & Cannizzaro, C. (2015) · Alcohol · doi:10.1016/j.alcohol.2015.01.002 · Cited by 32 · see citing works
Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB Rat Line
Israel, Y., Karahanian, E., Ezquer, F. E., Morales, P., Ezquer, M., Rivera‐Meza, M., Herrera‐Marschitz, M., & Quintanilla, M. E. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00057 · Cited by 31 · see citing works
“In the presence of ethanol, acetate levels in brain homogenates are 7-fold greater than those of acetaldehyde (Zimatkin et al., 2006).”
BackgroundMethodInfluentialMartí‐Prats, L., Sánchez-Catalán, M. J., Orrico‐Sánchez, A., Zornoza, T., Polache, A., & Granero, L. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.047 · Cited by 31 · see citing works
Synaptic proteome changes in the superior frontal gyrus and occipital cortex of the alcoholic brain
Etheridge, N., Lewohl, J. M., Mayfield, R. D., Harris, R. A., & Dodd, P. R. (2009) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200800202 · Cited by 31 · see citing works
“Excessive consumption of alcohol causes both of these stresses: ethanol metabolism pathways produce free radicals that cause oxidative damage in the liver [54, 55] and brain [56], and chronic alcohol abuse enhances excitotoxicity through altered regulation of the neurotransmitters gaminobutyric acid and glutamate, and…”
Transgenic Mouse Models for Alcohol Metabolism, Toxicity, and Cancer
Heit, C., Dong, H., Chen, Y., Shah, Y. M., Thompson, D. C., & Vasiliou, V. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-09614-8_22 · Cited by 30 · see citing works
“Catalase appears to play an important role in ethanol metabolism in the brain [14, 15].”
BackgroundSelf-citationBrief alcohol exposure alters transcription in astrocytes via the heat shock pathway
Pignataro, L., Varodayan, F. P., Tannenholz, L., Protiva, P., & Harrison, N. L. (2013) · Brain and Behavior · doi:10.1002/brb3.125 · Cited by 30 · see citing works
“It is thought that that this immune response may be triggered in part by the appearance of metabolic adducts formed from the reaction of the ethanol metabolite acetaldehyde with proteins, nucleic acids, and phospholipids (Deitrich et al. 2006; Zimatkin et al. 2006).”
BackgroundEthanol and acetaldehyde alter NTPDase and 5′-nucleotidase from zebrafish brain membranes
Rico, E. P., Rosemberg, D. B., Senger, M. R., Arizi, M. D. B., Dias, R. D., Souto, A. A., Bogo, M. R., & Bonan, C. D. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.06.034 · Cited by 30 · see citing works
“…that there are two oxidative pathways for metabolizing ethanol to acetaldehyde in brain: catalase may be responsible for about 60% of the process (Zimatkin et al., 2006) while cytocrome P450 (CYP2E1) is involved in the metabolic conversion of ethanol to reactive oxygen species (Sun and Sun,…”
Li, Q., & Ren, J. T. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.01.005 · Cited by 30 · see citing works
“…of lipoprotein and apolipoprotein particles, metabolic and excitotoxic changes as well as genetic predisposition (Hannuksela et al. 2002;Kucera et al. 2002;Patel et al. 1997;Zhang et al. 2004;Zimatkin et al. 2006), none of the scenarios received full validation from clinical and experimental data.”
Łaniewska-Dunaj, M., Jelski, W., Orywal, K., Kochanowicz, J., Rutkowski, R., & Szmitkowski, M. (2013) · Neurochemical Research · doi:10.1007/s11064-013-1053-9 · Cited by 29 · see citing works
“Aldehyde dehydrogenase plays the crucial role in the further oxidation of ethanol-derived acetaldehyde in brain cells [6].”
InfluentialTolerance to Disulfiram Induced by Chronic Alcohol Intake in the Rat
Tampier, L., Quintanilla, M. E., & Israel, Y. (2008) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2008.00658.x · Cited by 29 · see citing works
Pardo, M., Betz, A. J., Miguel, N. S., López‐Cruz, L., Salamone, J. D., & Correa, M. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00081 · Cited by 29 · see citing works
Increased brain nitric oxide levels following ethanol administration
Finnerty, N. J., O’Riordan, S. L., Klamer, D., Lowry, J., & Pålsson, E. (2015) · Nitric Oxide · doi:10.1016/j.niox.2015.03.002 · Cited by 26 · see citing works
Rutkoski, C. F., Macagnan, N., Folador, A., Skovronski, V. J., do Amaral, A. M. B., Leitemperger, J., Costa, M. D., Hartmann, P. A., Müller, C., Loro, V. L., et al. (2020) · Environmental Science and Pollution Research · doi:10.1007/s11356-020-10798-w · Cited by 27 · see citing works
Müller, T. E., Nunes, M. E. M., Rodrigues, N. R., Fontana, B. D., Hartmann, D. D., Franco, J. L., & Rosemberg, D. B. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104584 · Cited by 27 · see citing works
Acetaldehyde Oral Self‐Administration: Evidence from the Operant‐Conflict Paradigm
Cacace, S., Plescia, F., Barberi, I., & Cannizzaro, C. (2012) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01725.x · Cited by 26 · see citing works
Chapp, A. D., Gui, L., Huber, M. J., Liu, J., Larson, R. A., Zhu, J., Carter, J. R., & Chen, Q. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00005.2014 · Cited by 25 · see citing works
Ibrahim, B. M., Fan, M., & Abdel‐Rahman, A. A. (2014) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12363 · Cited by 26 · see citing works
“Ethanol is metabolized via ADH and catalase to ACA, which is eliminated by ALDH2 (ElMas and Abdel-Rahman, 2012a, Quertemont et al., 2005, Zimatkin et al., 2006).”
BackgroundEthanol intake and ethanol-induced locomotion and locomotor sensitization in Cyp2e1 knockout mice
Correa, M., Viaggi, C., Escrig, M. A., Pascual, M., Guerri, C., Vaglini, F., Aragón, C. M. G., & Corsini, G. U. (2009) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328324e726 · Cited by 26 · see citing works
Xenobiotic Metabolising Enzymes: Impact on Pathologic Conditions, Drug Interactions and Drug Design
Rekka, E. A., Kourounakis, P. N., & Pantelidou, M. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190129122727 · Cited by 26 · see citing works
Ledesma, J. C., & Aragón, C. M. G. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2831-9 · Cited by 25 · see citing works
Belém-Filho, I. J. A., Ribera, P. C., Nascimento, A. L., Gomes, A. R. Q., Lima, R. R., Lopez, M. E. C., Monteiro, M. C., Fontes-Júnior, E. A., Lima, M. D. O., & Maia, C. D. S. F. (2018) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2018.04.021 · Cited by 25 · see citing works
Biochemical Mechanisms Associating Alcohol Use Disorders with Cancers
Rodriguez, F. D., & Coveñas, R. (2021) · Cancers · doi:10.3390/cancers13143548 · Cited by 27 · see citing works
“Although this hemecontaining enzyme is present in many tissues, it does not represent the main route for alcohol elimination [51,52]; however, its role in brain tissue is relevant [47].”
BackgroundJamal, M., Ameno, K., Miki, T., Wang, W., Kumihashi, M., Isse, T., Kawamoto, T., Kitagawa, K., Nakayama, K. I., Ijiri, I., et al. (2009) · Brain Research · doi:10.1016/j.brainres.2009.07.099 · Cited by 24 · see citing works
Liu, M., Zhang, Q., Pei, L., Zou, Y., Chen, G., & Wang, H. (2019) · Epigenetics · doi:10.1080/15592294.2019.1581595 · Cited by 24 · see citing works
“Ethanol is one of the most widely consumed substances of abuse [1].”
BackgroundSwaminathan, K., Clemens, D. L., & Dey, A. (2013) · Life Sciences · doi:10.1016/j.lfs.2012.12.014 · Cited by 23 · see citing works
“7(a), pre-incubation of HepG2 cells with 0.1 mM PIC, another specific CYP2E1 inhibitor did not lead to decrease in viability and 0.1 mM PIC treatment increased the viability of VL-17A cells to 104% (pb0.”
BackgroundMethodInfluentialInduction of brain cytochrome P450 2E1 boosts the locomotor-stimulating effects of ethanol in mice
Ledesma, J. C., Miquel, M., Pascual, M., Guerri, C., & Aragón, C. M. G. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.05.018 · Cited by 23 · see citing works
Yorgason, J. T., Wadsworth, H. A., Anderson, E. J., Williams, B. M., Brundage, J., Hedges, D. M., Stockard, A. L., Jones, S. T., Arthur, S. B., Hansen, D. M., et al. (2021) · Addiction Biology · doi:10.1111/adb.13108 · Cited by 23 · see citing works
Jelski, W., Łaniewska-Dunaj, M., Orywal, K., Kochanowicz, J., Rutkowski, R., & Szmitkowski, M. (2014) · Neurochemical Research · doi:10.1007/s11064-014-1402-3 · Cited by 23 · see citing works
“Some investigations have shown that alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are present in the cells of human brain tissues [2, 3].”
Background
- Authors
- Zimatkin, S. M., Pronko, S. P., Vasiliou, V., Gonzalez, F. J., & Deitrich, R. A.
- Affiliations
- Grodno State Medical University (BY)
- University of Colorado Denver (US)
- National Institutes of Health (US)
- Corresponding author
- Zimatkin, Sergey M.
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2006-08-14
- Volume
- 30
- Issue
- 9
- Pages
- 1500-1505
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- OpenAlex
- W1970756197
- Cited by
- 241
- References
- 25
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 6 · 2023: 10 · 2022: 7 · 2021: 14 · 2020: 11 · 2019: 24 · 2018: 11 · 2017: 20 · 2016: 8 · 2015: 14 · 2014: 15 · 2013: 23 · 2012: 12
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50aa003527-25, 5k05aa000093-12, 5r21aa012284-02)
- National Institute on Alcohol Abuse and Alcoholism (R01AA011885, K05 AA 00093, R01 AA 12650, P50 AA03527, R21-AA12284, R01AA012650)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
- Keywords
- ethanol oxidation, brain, catalase, CYP2E1, alcohol dehydrogenase, aldehyde dehydrogenase, acetaldehyde, acetate, enzyme inhibitors, subcellular fractions, peroxisomes, microsomes, alcohol metabolism, rodents, mice, rats, 4-methylpyrazole, 3-amino-1,2,4-triazole
- MeSH terms
- Acetaldehyde, Acetates, Alcohol Dehydrogenase, Ethanol, Animals, Brain, Catalase, Central Nervous System Depressants, DNA, Enzyme Inhibitors, Genetic Markers, Male, Mice, Inbred C3H, Oxidation-Reduction, Subcellular Fractions, Genetic Variation, Rats, Wistar, Mice, Knockout, Cytochrome P-450 CYP2E1, Mice, Rats, Cytochrome P-450 CYP2E1 Inhibitors
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
