Mammalian alcohol dehydrogenase of higher classes: analyses of human ADH5 and rat ADH6

Höög, Jan‐Olov; Brandt, Margareta; Hedberg, Jesper J.; Strömberg, Patrik

doi:10.1016/s0009-2797(00)00264-7

Cited by 16 publications

(7 citation statements)

References 19 publications

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“…Glu-67 and Arg-368 are highly conserved essential amino acids important to the catalytic mechanism of this enzyme (Sanghani et al, 2006). Splice variants of ADH5 exist and result in the production of truncated proteins; however, their functional relevance has not been documented (Höög et al, 2001). …”

Section: Adh5: Structure/localizationmentioning

confidence: 99%

The role of S-nitrosoglutathione reductase (GSNOR) in human disease and therapy

Barnett

Buxton

2017

Critical Reviews in Biochemistry and Molecular Biology

117

101

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S-nitrosoglutathione reductase (GSNOR), or ADH5, is an enzyme in the alcohol dehydrogenase (ADH) family. It is unique when compared to other ADH enzymes in that primary short-chain alcohols are not its principle substrate. GSNOR metabolizes S-nitrosoglutathione (GSNO), S-hydroxymethylglutathione (the spontaneous adduct of formaldehyde and glutathione), and some alcohols. GSNOR modulates reactive nitric oxide (•NO) availability in the cell by catalyzing the breakdown of GSNO, and indirectly regulates S-nitrosothiols (RSNOs) through GSNO-mediated protein S-nitrosation. The dysregulation of GSNOR can significantly alter cellular homeostasis, leading to disease. GSNOR plays an important regulatory role in smooth muscle relaxation, immune function, inflammation, neuronal development, and cancer progression, among many other processes. In recent years, the therapeutic inhibition of GSNOR has been investigated to treat asthma, cystic fibrosis and interstitial lung disease (ILD). The direct action of •NO on cellular pathways, as well as the important regulatory role of protein S-nitrosation, are closely tied to GSNOR regulation and define this enzyme as an important therapeutic target.

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Section: Adh5: Structure/localizationmentioning

confidence: 99%

The role of S-nitrosoglutathione reductase (GSNOR) in human disease and therapy

Barnett

Buxton

2017

Critical Reviews in Biochemistry and Molecular Biology

117

101

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“…Adh5 genes have been reported in human (Yasunami et al, 1991;Stromberg and Hö ög, 2000), deer mouse (Peromyscus maniculatus) (Zheng et al, 1993) and rat (Hö ö g and Brandt, 1995). Multiple mRNAs are produced by alternative polyadenylation and splicing events (Stromberg and Hö ö g, 2000;Hö ö g et al, 2001a). The longest transcript (3.3 kb) was found to be the most prominent.…”

Section: Evolution Of the Mdr-adh Family R Gonzàlez-duarte And R Albalatmentioning

confidence: 99%

Merging protein, gene and genomic data: the evolution of the MDR-ADH family

Gonzàlez‐Duarte

Albalat

2005

Heredity

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Multiple members of the MDR-ADH (MDR: Medium-chain dehydrogenases/reductases; ADH: alcohol dehydrogenase) family are found in vertebrates, although the enzymes that belong to this family have also been isolated from bacteria, yeast, plant and animal sources. Initial understanding of the physiological roles and evolution of the family relied on biochemical studies, protein alignments and protein structure comparisons. Subsequently, studies at the genetic level yielded new information: the expression pattern, exon-intron distribution, in silico-derived protein sequences and murine knockout phenotypes. More recently, genomic and EST databases have revealed new family members and the chromosomal location and position in the cluster of both the first and new forms. The data now available provide a comprehensive scenario, from which a reliable picture of the evolutionary history of this family can be made.

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“…Close to the origin of mammals, ADH1 duplicated giving rise to ADH4, a highly retinoid-active enzyme [7,8] present in eye, skin and gastric tissues [9-11]. The most evolutionarily recent classes in mammals are ADH5 and ADH6 [12], the latter being absent in primates [13]. These two classes, identified at DNA level, are the most divergent within mammalian ADHs.…”

Section: Introductionmentioning

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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Mammalian alcohol dehydrogenase of higher classes: analyses of human ADH5 and rat ADH6

Cited by 16 publications

References 19 publications

The role of S-nitrosoglutathione reductase (GSNOR) in human disease and therapy

The role of S-nitrosoglutathione reductase (GSNOR) in human disease and therapy

Merging protein, gene and genomic data: the evolution of the MDR-ADH family

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

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