Alcohol dehydrogenase in human tissues: localisation of transcripts coding for five classes of the enzyme

Estonius, Mats; Svensson, Stefan; Höög, Jan‐Olov

doi:10.1016/s0014-5793(96)01204-5

Cited by 125 publications

(78 citation statements)

References 37 publications

(19 reference statements)

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“…ADH was detected in human fetal tissues at a mean gestational age of 11 weeks (Smith et al, 1971). Estonius et al (1996) detected Class I ADH mRNA transcript as early as 18 weeks of gestation in human fetal lung, liver, and kidney, but not in the brain. In medaka, we have identified developmentally-expressed ADH enzyme mRNAs (Adh5 and Adh8).…”

Section: Discussionmentioning

confidence: 95%

Japanese medaka (Oryzias latipes): developmental model for the study of alcohol teratology

Wang

Williams

Haasch

et al. 2006

Birth Defects Research Pt B

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BACKGROUND: Animal models are necessary to investigate the mechanism of alcohol-induced birth defects. We have used Japanese medaka (Oryzias latipes) as a non-mammalian model to elucidate the molecular mechanism(s) of ethanol teratogenesis. METHODS: Medaka eggs, within 1 hr post-fertilization (hpf) were exposed to waterborne ethanol (0-1000 mM) in hatching solution for 48 hr. Embryo development was observed daily until 10 days post-fertilization (dpf). The concentration of embryonic ethanol was determined enzymatically. Cartilage and bones were stained by Alcian blue and calcein, respectively and skeletal and cardiovascular defects were assessed microscopically. Genetic gender of the embryos was determined by PCR. Levels of two isoenzymes of alcohol dehydrogenase (Adh) mRNAs were determined by semi-quantitative and real-time RT-PCR. RESULTS: The concentration of ethanol required to cause 50% mortality (LC 50 ) in 10 dpf embryos was 568 mM, however, the embryo absorbed only 15-20% of the waterborne ethanol at all ethanol concentrations. The length of the lower jaw and calcification in tail fin cartilaginous structures were reduced by ethanol exposure. Active blood circulation was exhibited at 501 hpf in embryos treated with 0-100 mM ethanol; active circulation was delayed and blood clots developed in embryos treated with 200-400 mM ethanol. The deleterious effects of ethanol were not gender-specific. Moreover, ethanol treatment was unable to alter the constitutive expression of either Adh5 or Adh8 mRNA in the medaka embryo. CONCLUSIONS: Preliminary results suggested that embryogenesis in medaka was significantly affected by ethanol exposure. Phenotypic features normally associated with ethanol exposure were similar to that observed in mammalian models of fetal alcohol syndrome. The results further indicated that medaka embryogenesis might be used as an alternative non-mammalian model for investigating specific alterations in gene expression as a means to understand the molecular mechanism(s) of ethanol-induced birth defects.

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Section: Discussionmentioning

confidence: 95%

Japanese medaka (Oryzias latipes): developmental model for the study of alcohol teratology

Wang

Williams

Haasch

et al. 2006

Birth Defects Research Pt B

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“…Class I ADH has also been found in blood vessels (Allali-Hassani et al 1997), a finding relevant to the alcohol-induced flush reaction. Surveys of ADH expression patterns in human tissue have been published (Engeland & Maret, 1993;Estonius et al 1996). The expression of ADH in gut mucosa and breast is relevant to studies on the effect of alcohol on cancers of these organs.…”

Section: Alcohol Dehydrogenasesmentioning

confidence: 99%

Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology

et al. 2004

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Alcohol dehydrogenase (ADH) and mitochondrial aldehyde dehydrogenase (ALDH2) are responsible for metabolizing the bulk of ethanol consumed as part of the diet and their activities contribute to the rate of ethanol elimination from the blood. They are expressed at highest levels in liver, but at lower levels in many tissues. This pathway probably evolved as a detoxification mechanism for environmental alcohols. However, with the consumption of large amounts of ethanol, the oxidation of ethanol can become a major energy source and, particularly in the liver, interferes with the metabolism of other nutrients. Polymorphic variants of the genes for these enzymes encode enzymes with altered kinetic properties. The pathophysiological effects of these variants may be mediated by accumulation of acetaldehyde; high-activity ADH variants are predicted to increase the rate of acetaldehyde generation, while the low-activity ALDH2 variant is associated with an inability to metabolize this compound. The effects of acetaldehyde may be expressed either in the cells generating it, or by delivery of acetaldehyde to various tissues by the bloodstream or even saliva. Inheritance of the high-activity ADH β2, encoded by the ADH2*2 gene, and the inactive ALDH2*2 gene product have been conclusively associated with reduced risk of alcoholism. This association is influenced by gene–environment interactions, such as religion and national origin. The variants have also been studied for association with alcoholic liver disease, cancer, fetal alcohol syndrome, CVD, gout, asthma and clearance of xenobiotics. The strongest correlations found to date have been those between the ALDH2*2 allele and cancers of the oro-pharynx and oesophagus. It will be important to replicate other interesting associations between these variants and other cancers and heart disease, and to determine the biochemical mechanisms underlying the associations.

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“…The human ADH5 mRNA is developmentally expressed in the fetal tissues including the brain, lung, liver, and kidney (32). The medium-chain class III alcohol dehydrogenase in Drosophila melanogaster is expressed throughout the larval, pupal, and adult life stages of the fly (33).…”

Section: Isolation and Analysis Of Cdna Coding For Zebrafish Adh8amentioning

confidence: 99%

Two Zebrafish Alcohol Dehydrogenases Share Common Ancestry with Mammalian Class I, II, IV, and V Alcohol Dehydrogenase Genes but Have Distinct Functional Characteristics

Reimers

Hahn

Tanguay

2004

Journal of Biological Chemistry

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Ethanol is teratogenic to many vertebrates. We are utilizing zebrafish as a model system to determine whether there is an association between ethanol metabolism and ethanol-mediated developmental toxicity. Here we report the isolation and characterization of two cDNAs encoding zebrafish alcohol dehydrogenases (ADHs). Phylogenetic analysis of these zebrafish ADHs indicates that they share a common ancestor with mammalian class I, II, IV, and V ADHs. The genes encoding these zebrafish ADHs have been named Adh8a and Adh8b by the nomenclature committee. Both genes were genetically mapped to chromosome 13. The 1450-bp Adh8a is 82, 73, 72, and 72% similar at the amino acid level to the Baltic cod ADH8 (previously named ADH1), the human ADH1B2, the mouse ADH1, and the rat ADH1, respectively. Also, the 1484-bp Adh8b is 77, 68, 67, and 66% similar at the amino acid level to the Baltic cod ADH8, the human ADH1B2, the mouse ADH1, and the rat ADH1, respectively. ADH8A and ADH8B share 86% amino acid similarity. To characterize the functional properties of ADH8A and ADH8B, recombinant proteins were purified from SF-9 insect cells. Kinetic studies demonstrate that ADH8A metabolizes ethanol, with a V max of 13.4 nmol/min/mg protein, whereas ADH8B does not metabolize ethanol. The ADH8A K m for ethanol as a substrate is 0.7 mM. 4-Methyl pyrazole, a classical competitive inhibitor of class I ADH, failed to inhibit ADH8A. ADH8B has the capacity to efficiently biotransform longer chain primary alcohols (>5 carbons) and S-hydroxymethlyglutathione, whereas ADH8A does not efficiently metabolize these substrates. Finally, mRNA expression studies indicate that both ADH8A and ADH8B mRNA are expressed during early development and in the adult brain, fin, gill, heart, kidney, muscle, and liver. Together these results indicate that class Ilike ADH is conserved in zebrafish, albeit with mixed functional properties.Fetal alcohol syndrome in children born to women who consumed alcohol during pregnancy was first described by Jones and colleagues in 1973 (1). Fetal alcohol syndrome is characterized by a delay in development, cardiac abnormalities (1), central nervous abnormalities, abnormal craniofacial features, and intellectual delays (1, 2). The teratogenic properties of ethanol have been firmly established; however, the underlying mechanism(s) of toxicity remain unclear. Two molecular mechanisms have been proposed: direct ethanol effects and the indirect effects associated with acetaldehyde formation and oxidative stress (3). The ability of ethanol to cause developmental anomalies has been demonstrated in mice, rats, Drosophila melanogaster, and chickens (4 -7). Zebrafish are well suited for genetic studies (reviewed in Ref. 8). Zebrafish embryos exposed to ethanol display craniofacial abnormalities, cardiac and structural malformations, and development delay (9 -11). Visual function was affected in embryos exposed to 1.5% ethanol during development (12). Recent studies indicate that three adult strains of zebrafish display different behavior...

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Alcohol dehydrogenase in human tissues: localisation of transcripts coding for five classes of the enzyme

Cited by 125 publications

References 37 publications

Japanese medaka (Oryzias latipes): developmental model for the study of alcohol teratology

Japanese medaka (Oryzias latipes): developmental model for the study of alcohol teratology

Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology

Two Zebrafish Alcohol Dehydrogenases Share Common Ancestry with Mammalian Class I, II, IV, and V Alcohol Dehydrogenase Genes but Have Distinct Functional Characteristics

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