Impaired acetaldehyde oxidation in alcoholics

Palmer, K R; Jenkins, W. J.

doi:10.1136/gut.23.9.729

Cited by 74 publications

(17 citation statements)

References 25 publications

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“…Blood levels of AcH have been shown to inversely correlate with blood and hepatic ALDH2 ac-tivity and to mainly affect AcH levels during alcohol consumption, even though polymorphisms of the alcohol dehydrogenase gene are also known to influence AcH levels [1][2][3][4][5] . The loss of ALDH2 activity has been reported to influence susceptibility not only to acute adverse effects of alcohol consumption like nausea and headache, but also to severe alcohol-related health risks, particularly esophageal squamous cell carcinoma (ESCC) [6] .…”

Section: Introductionmentioning

confidence: 99%

Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients

Nassab

Rhein²,

Hagemeier³

et al. 2015

Eur Addict Res

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Acetaldehyde, the carcinogenic metabolite of ethanol known to provoke aversive symptoms of alcohol consumption, is predominantly eliminated by aldehyde dehydrogenase 2 (ALDH2). Reduced ALDH2 activity correlates with low alcohol tolerance and low risk for alcohol dependence. The ALDH2 promoter polymorphism rs886205 (A>G) is associated with decreased promoter activity, but a molecular mechanism and allele-dependent ALDH2 protein expression has not been described yet. On the basis of allele-dependent epigenetic effects, we analyzed the rs886205 genotype, methylation rates of cytosine-phosphatidyl-guanine (CpG)-sites within a regulatory promoter region and ALDH2 protein levels in 82 alcohol-dependent patients during a 2-week withdrawal and compared them to 34 matched controls. Patients without the G-allele of rs886205 showed higher methylation of the promoter region than controls and readily adapted epigenetically as well as on protein level during withdrawal, while patients with the G-allele displayed retarded methylation readjustment and no change in ALDH2 protein levels. Our data provide novel insights into an unknown genetic-epigenetic interaction, revealing impaired ALDH2 protein expression in patients with the G-allele of rs886205. Additionally, we checked for an association between rs886205 and protection against alcohol dependence and found a trend association between the G-allele and protection against alcohol dependence that needs replication in a larger Caucasian cohort.

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Section: Introductionmentioning

confidence: 99%

Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients

Nassab

Rhein²,

Hagemeier³

et al. 2015

Eur Addict Res

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“…Higher blood acetaldehyde levels in alcoholics have been reported to be due to reduced acetaldehyde oxidation rates rather than increased rates of formation [14]. High levels of blood acetaldehyde imply a remarkable elevation of acetaldehyde in the hepatocytes [10], which may inhibit ethanol oxidation.…”

Section: Discussionmentioning

confidence: 99%

Impaired acetaldehyde metabolism in partially hepatectomized rats

et al. 1985

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Two-thirds hepatectomy in rats resulted in elevated blood ethanol and acetaldehyde levels as compared to those of sham operated and CCl4-induced toxic injured rats. The acetaldehyde/ethanol ratio increased also. Although the liver mass regenerated within 3 days, ethanol metabolism remained disturbed. Mitochondrial aldehyde dehydrogenase activity was significantly diminished only following partial hepatectomy. The results suggest that abnormal ethanol and especially acetaldehyde metabolism in partially hepatectomized rats is not due simply to reduced liver tissue but to a diminished aldehyde dehydrogenase activity in the remaining tissue.

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“…In volunteers the blood concentration of ac etaldehyde following intake of 0.5 g/kg of alcohol is 0.5-1.3 pmol/1 [8]. Although somewhat higher acetaldehyde levels have been measured in alcoholics and in mothers of FAS children, the activity of placental ALDH as well as its affinity for acetaldehyde are both far too low to prevent passage of acetaldehyde from the mother to the fetus [8][9][10]. In experimental animals, the pla centa constitutes a relative barrier to acetal dehyde [3,4], However, as shown in this study, because of the properties of the pla cental ALDH in alcoholics, the role of pla cental oxidation as a possible placental bar rier to acetaldehyde is negligible.…”

Section: Discussionmentioning

confidence: 99%

Placental Alcohol Metabolism in Chronic Alcohol Abuse

Andersson

Halmesmäki²,

Koivusalo³

et al. 1989

Neonatology

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The activities of aldehyde dehydrogenase (ALDH; EC 1.2.1.3) and alcohol dehydrogenase (ADH; EC 1.1.1.1) were measured in term placentas of 13 alcoholic women and 16 matched controls. With acetaldehyde 8 mmol/l as substrate, the ALDH activity was 29.1 ± 12.2 and 34.4 ± 15.3 mU/g of wet weight (mean ± SD; p > 0.4) for alcoholics and controls, respectively. With 50 μmol of acetaldehyde, ALDH activity was undetectable in both groups. No ADH activity could be detected in the placentas. The weights of placentas and newborns were significantly lower in the alcoholic group (placentas: 526 ± 116 vs. 653 ± 77 g, p < 0.005; newborns 2,878 ± 417 vs. 3,595 ± 346 g, p < 0.001). The results suggest that in chronic alcohol abuse, the placenta plays a negligible role in the metabolism of ethanol and acetaldehyde.

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Impaired acetaldehyde oxidation in alcoholics

Cited by 74 publications

References 25 publications

Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients

Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients

Impaired acetaldehyde metabolism in partially hepatectomized rats

Placental Alcohol Metabolism in Chronic Alcohol Abuse

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