A Novel Subtype of Class II Alcohol Dehydrogenase in Rodents

Svensson, Stefan; Strömberg, Patrik; Höög, Jan‐Olov

doi:10.1074/jbc.274.42.29712

Cited by 37 publications

(26 citation statements)

References 54 publications

(42 reference statements)

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“…We have shown here that AKR has also evolved convergently with SDR and MDR in terms of ethanol and ROL metabolism. The (␣/␤) 8 barrel of the AKR tertiary structure, with a conserved core and variable loops in outer domains, responsible for substrate binding, represents a highly adaptable scaffold, able to evolve and develop distinct functions (62) as the retinoid oxidoreduction, here demonstrated. The inclusion of the AKR superfamily in the metabolism of retinoids defines a new scenario where the triad SDR-MDR-AKR would participate in the cellular regulation of the essential signaling function of retinoids.…”

Section: Discussionmentioning

confidence: 84%

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A Vertebrate Aldo-keto Reductase Active with Retinoids and Ethanol

Crosas

Cederlund

Torres

et al. 2001

Journal of Biological Chemistry

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Enzymes of the short chain and medium chain dehydrogenase/reductase families have been demonstrated to participate in the oxidoreduction of ethanol and retinoids. Mammals and amphibians contain, in the upper digestive tract mucosa, alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, active with ethanol and retinol. In the present work, we searched for a similar enzyme in an avian species (Gallus domesticus). We found that chicken does not contain the homologous enzyme from the medium chain dehydrogenase/reductase family but an oxidoreductase from the aldo-keto reductase family, with retinal reductase and alcohol dehydrogenase activities. The amino acid sequence shows 66 -69% residue identity with the aldose reductase and aldose reductase-like enzymes. Chicken aldo-keto reductase is a monomer of M r 36,000 expressed in eye, tongue, and esophagus. The enzyme can oxidize aliphatic alcohols, such as ethanol, and it is very efficient in all-trans-and 9-cis-retinal reduction (k cat /K m ‫؍‬ 5,300 and 32,000 mM ؊1 ⅐min ؊1 , respectively). This finding represents the inclusion of the aldo-keto reductase family, with the (␣/␤) 8 barrel structure, into the scenario of retinoid metabolism and, therefore, of the regulation of vertebrate development and tissue differentiation.

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Section: Discussionmentioning

confidence: 84%

“…ADH1 is the classical enzyme responsible for liver ethanol metabolism, which also exhibits activity with retinoids (6,7). ADH2 is a liver enzyme that may marginally contribute to ethanol and retinoid metabolisms (8,9). ADH3 is a glutathionedependent formaldehyde dehydrogenase (FALDH) inactive with retinoids (6).…”

mentioning

confidence: 99%

A Vertebrate Aldo-keto Reductase Active with Retinoids and Ethanol

Crosas

Cederlund

Torres

et al. 2001

Journal of Biological Chemistry

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“…Class II can be divided in two structurally and functionally distinct subgroups [70]. The first one exhibits a low activity with ethanol and comprises mouse and rat ADH2, both showing Pro47, and rabbit ADH2B, which lacks a His residue at both positions 47 or 51 (Table 6).…”

Section: Discussionmentioning

confidence: 99%

The Xenopusalcohol dehydrogenase gene family: characterization and comparative analysis incorporating amphibian and reptilian genomes

et al. 2014

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BackgroundThe alcohol dehydrogenase (ADH) gene family uniquely illustrates the concept of enzymogenesis. In vertebrates, tandem duplications gave rise to a multiplicity of forms that have been classified in eight enzyme classes, according to primary structure and function. Some of these classes appear to be exclusive of particular organisms, such as the frog ADH8, a unique NADP+-dependent ADH enzyme. This work describes the ADH system of Xenopus, as a model organism, and explores the first amphibian and reptilian genomes released in order to contribute towards a better knowledge of the vertebrate ADH gene family.ResultsXenopus cDNA and genomic sequences along with expressed sequence tags (ESTs) were used in phylogenetic analyses and structure-function correlations of amphibian ADHs. Novel ADH sequences identified in the genomes of Anolis carolinensis (anole lizard) and Pelodiscus sinensis (turtle) were also included in these studies. Tissue and stage-specific libraries provided expression data, which has been supported by mRNA detection in Xenopus laevis tissues and regulatory elements in promoter regions. Exon-intron boundaries, position and orientation of ADH genes were deduced from the amphibian and reptilian genome assemblies, thus revealing syntenic regions and gene rearrangements with respect to the human genome. Our results reveal the high complexity of the ADH system in amphibians, with eleven genes, coding for seven enzyme classes in Xenopus tropicalis. Frogs possess the amphibian-specific ADH8 and the novel ADH1-derived forms ADH9 and ADH10. In addition, they exhibit ADH1, ADH2, ADH3 and ADH7, also present in reptiles and birds. Class-specific signatures have been assigned to ADH7, and ancestral ADH2 is predicted to be a mixed-class as the ostrich enzyme, structurally close to mammalian ADH2 but with class-I kinetic properties. Remarkably, many ADH1 and ADH7 forms are observed in the lizard, probably due to lineage-specific duplications. ADH4 is not present in amphibians and reptiles.ConclusionsThe study of the ancient forms of ADH2 and ADH7 sheds new light on the evolution of the vertebrate ADH system, whereas the special features showed by the novel forms point to the acquisition of new functions following the ADH gene family expansion which occurred in amphibians.

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“…The ADH6b clone is a 626-bp partial sequence called IMAGE 1023849 (AI506561.1) obtained from Stratagene. The ADH4 (class II) cDNA was prepared (G. Duester) by RT-PCR of mouse liver using the published sequence of mouse ADH4 cDNA (Svensson et al 1999). …”

Section: Northern Analysis Of Rna Expressionmentioning

confidence: 99%

Tissue Expression Pattern of Class II and Class V Genes Found in the Adh Complex on Mouse Chromosome 3

et al. 2008

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The alcohol dehydrogenase enzymes in mice and humans are encoded by a linked group of genes in the same transcriptional orientation. The enzymes play important roles in alcohol metabolism and retinoid signaling and homeostasis. The expression patterns at the mRNA level of the mouse Adh4 (class II) gene and the recently identified Adh6a and Adh6b genes (class V) are now reported to complete this analysis for the entire family. Adh4 is expressed at high levels in liver and is detectable in small intestine and testes. Adh6b is expressed in liver but Adh6a is not. Adh6a is expressed at high levels in small intestine while Adh6b is not. Adh6a expression is detectable in the female adrenal and not at all in the male adrenal, but Adh6b is expressed at moderate levels in both sexes. Although Adh6a and Adh6b have expression patterns different from each other, neither expresses like any other gene in the complex, suggesting different control mechanisms and possibly different functions.

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A Novel Subtype of Class II Alcohol Dehydrogenase in Rodents

Cited by 37 publications

References 54 publications

A Vertebrate Aldo-keto Reductase Active with Retinoids and Ethanol

A Vertebrate Aldo-keto Reductase Active with Retinoids and Ethanol

The Xenopusalcohol dehydrogenase gene family: characterization and comparative analysis incorporating amphibian and reptilian genomes

Tissue Expression Pattern of Class II and Class V Genes Found in the Adh Complex on Mouse Chromosome 3

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