The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
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.
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“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]
In the citing paper
“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]
In the citing paper
“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]
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Metadata
- 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
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