Expression Pattern, Ethanol‐Metabolizing Activities, and Cellular Localization of Alcohol and Aldehyde Dehydrogenases in Human Small Intestine

Chiang, Chien-Ping; Wu, Chew-Wun; Lee, Shiao-Pieng; Ho, Ji-Lin; Lee, Shou-Lun; Nieh, Shin; Yin, Shih‐Jiun

doi:10.1111/j.1530-0277.2012.01836.x

Cited by 31 publications

(31 citation statements)

References 60 publications

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“…Immediately after the completion of electrophoresis, each gel section was stained for ALDH enzyme activity in a solution containing 1 mM NAD + , 0.5 mM nitroblue tetrazolium, 1 mM phenazine methosulfate, 100 mM Tris·HCl at pH 7.5, and 10 mM acetaldehyde as a substrate. After 30 min staining in the dark, the staining reaction was terminated by substitution of the staining solution with H 2 O, as described in a previously published method (30).…”

Section: Methodsmentioning

confidence: 99%

“…Because all tissues contain several ALDH family members, we used isoelectric focusing to separate them and measured in-gel ALDH activity using NAD + -coupled phenazine methosulfate/nitroblue tetrazolium color reaction (30). The calculated pI values for mouse ALDH2 and ALDH3A1 are 7.5 and 6.5, respectively.…”

Section: Metabolism Of Acetaldehyde In the Presence Of Alda-1 Togethementioning

confidence: 99%

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Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo

Chen

Cruz

Mochly‐Rosen

2015

Proc. Natl. Acad. Sci. U.S.A.

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Correcting a genetic mutation that leads to a loss of function has been a challenge. One such mutation is in aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2. This mutation is present in ∼0.6 billion East Asians and results in accumulation of toxic acetaldehyde after consumption of ethanol. To temporarily increase metabolism of acetaldehyde in vivo, we describe an approach in which a pharmacologic agent recruited another ALDH to metabolize acetaldehyde. We focused on ALDH3A1, which is enriched in the upper aerodigestive track, and identified Alda-89 as a small molecule that enables ALDH3A1 to metabolize acetaldehyde. When given together with the ALDH2-specific activator, Alda-1, Alda-89 reduced acetaldehyde-induced behavioral impairment by causing a rapid reduction in blood ethanol and acetaldehyde levels after acute ethanol intoxication in both wild-type and ALDH2-deficient, ALDH2*1/*2, heterozygotic knock-in mice. The use of a pharmacologic agent to recruit an enzyme to metabolize a substrate that it usually does not metabolize may represent a novel means to temporarily increase elimination of toxic agents in vivo.

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Section: Methodsmentioning

confidence: 99%

Section: Metabolism Of Acetaldehyde In the Presence Of Alda-1 Togethementioning

confidence: 99%

Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo

Chen

Cruz

Mochly‐Rosen

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Symptoms of hangover seem to be the combined result of dehydration, hormonal alterations, dysregulated cytokine pathways, and the toxic effects of alcohol and acetaldehyde [9]. Excessive ingestion of alcohol, whether acute or chronic, is responsible for a tremendous disease and disorder, not only alcoholic hepatitis, cirrhosis and hepatocarcinoma, but also a series of other dysfunctions including pancreatitis, cardiomyopathy, hypertension, stroke, and fetal alcohol syndrome [10][11][12][13]. Excessive consumption of alcohol also results in damage to the central nervous system, such as polyneuritis, cerebellar degeneration, alcoholic dementia, pellagra encephalopathy, Marchiafava-Bignami and Wernicke-Korsakoff syndromes [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Natural Products for the Prevention and Treatment of Hangover and Alcohol Use Disorder

Wang

Zhang

et al. 2016

Molecules

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Alcoholic beverages such as beer, wine and spirits are widely consumed around the world. However, alcohol and its metabolite acetaldehyde are toxic and harmful to human beings. Chronic alcohol use disorder or occasional binge drinking can cause a wide range of health problems, such as hangover, liver damage and cancer. Some natural products such as traditional herbs, fruits, and vegetables might be potential dietary supplements or medicinal products for the prevention and treatment of the problems caused by excessive alcohol consumption. The aim of this review is to provide an overview of effective natural products for the prevention and treatment of hangover and alcohol use disorder, and special emphasis is paid to the possible functional component(s) and related mechanism(s) of action.

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“…Archiwum Medycyny Sądowej i Kryminologii Archives of Forensic Medicine and Criminology tydami z atomem cynku w centrum katalitycznym o masie cząsteczkowej 40 kDa [15,16]. Tylko część z nich odgrywa istotną rolę w eliminacji etanolu, a dokładnie ADH1B i ADH1C występujące w wą-trobie oraz ADH7.…”

Section: Alcohol Dehydrogenaseunclassified

Variation in gastric alcohol dehydrogenase and the risk of alcohol dependence

Całka¹,

Ciesielka²,

Buszewicz³

et al. 2016

amsik

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StreszczenieUzależnienie od alkoholu stanowi problem zarówno medyczny, jak i społeczno-ekonomiczny. Jest zaliczane do chorób o charakterze wieloczynnikowym, czyli takich, za które odpowiadają relacje gen-gen oraz gen-środo-wisko. Wieloośrodkowe badania nad genetycznym podłożem alkoholizmu podkreślają znaczenie genów kodujących enzymy szlaku rozkładu etanolu w organizmie ludzkim, szczególnie dehydrogenazy alkoholowej (ADH) w rozwoju choroby. Z pięciu klas dehydrogenaz alkoholowych związek z uzależnieniem od alkoholu wykazują izoenzymy klasy I i IV. Klasa IV jest szczególnie interesująca ze względu na jej występowanie w górnym odcinku przewodu pokarmowego, głównie w żołądku. Nie wykazano aktywności tego enzymu w wątrobie. Polimorfizm pojedynczych nukleotydów (SNP) genu kodującego tę klasę, czyli ADH7, wpływa na jej aktywność utleniającą etanol w świetle żołądka i tym samym na metabolizm pierwszego przejścia ( FPM) tej substancji. Opublikowane wyniki różnych ośrodków badawczych pokazują, że konkretne zmiany typu SNP w genie ADH7 mają odmienne znaczenie dla ryzyka uzależnienia od alkoholu w zależności od badanej populacji.Słowa kluczowe: ADH7, alkoholizm, metabolizm pierwszego przejścia. AbstractAlcohol dependence is both a medical and socioeconomic problem. The disease is multifactorial, i.e. its development is attributable to gene-gene and gene-environment interactions. Multi-centre studies investigating the genetic background of alcoholism stress the role of genes encoding enzymes of the ethanol decomposition pathway in the human body, particularly alcohol dehydrogenase (ADH), in the development of alcohol dependence. Among five classes of alcohol dehydrogenases, class I and IV isoenzymes have been found to be associated with alcohol dependence. Class IV is of particular interest due to its occurrence in the upper gastrointestinal tract, mainly in the stomach. No activity of the enzyme has been demonstrated in the liver. Single nucleotide polymorphism (SNP) of the gene encoding ADH class IV (ADH7) affects its ethanol-oxidizing activity in the gastric lumen, thereby influencing the first-pass metabolism (FPM) of the substance. The findings published by various research centres have demonstrated that specific SNP changes in the ADH7 gene are of different significance for the risk of alcohol dependence according to the population studied.

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Expression Pattern, Ethanol‐Metabolizing Activities, and Cellular Localization of Alcohol and Aldehyde Dehydrogenases in Human Small Intestine

Cited by 31 publications

References 60 publications

Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo

Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo

Natural Products for the Prevention and Treatment of Hangover and Alcohol Use Disorder

Variation in gastric alcohol dehydrogenase and the risk of alcohol dependence

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