Evidence for the identity of glutathione‐dependent formaldehyde dehydrogenase and class III alcohol dehydrogenase

Koivusalo, Martti; Baumann, Marc; Uotila, Lasse

doi:10.1016/0014-5793(89)81797-1

Cited by 316 publications

(176 citation statements)

References 18 publications

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“…This yeast assimilates n-alkanes and the Fld enzyme is thought to be involved in the protection from the toxic effects of formaldehyde (Sasnauskas et al, 1992). The H. polymorpha Fld1p also showed 63-64% identity with dehydrogenase class III enzymes from humans and other higher eukaryotes (Holmquist and Vallee, 1991;Koivusalo et al, 1989;Giri et al, 1989).…”

Section: Resultsmentioning

confidence: 99%

Molecular characterization of the Hansenula polymorphaFLD1 gene encoding formaldehyde dehydrogenase

Baerends

Sulter

Jeffries

et al. 2001

Yeast

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Glutathione-dependent formaldehyde dehydrogenase (FLD) is a key enzyme required for the catabolism of methanol as a carbon source and certain primary amines, such as methylamine as nitrogen sources in methylotrophic yeasts. Here we describe the molecular characterization of the FLD1 gene from the yeast Hansenula polymorpha. Unlike the recently described Pichia pastoris homologue, the H. polymorpha gene does not contain an intron. The predicted FLD1 product (Fld1p) is a protein of 380 amino acids (ca. 41 kDa) with 82% identity to P. pastoris Fld1p, 76% identity to the FLD protein sequence from n-alkane-assimilating yeast Candida maltosa and 63-64% identity to dehydrogenase class III enzymes from humans and other higher eukaryotes. The expression of FLD1 is strictly regulated and can be controlled at two expression levels by manipulation of the growth conditions. The gene is strongly induced under methylotrophic growth conditions; moderate expression is obtained under conditions in which a primary amine, e.g. methylamine, is used as nitrogen source. These properties render the FLD1 promoter of high interest for heterologous gene expression. The availability of the H. polymorpha FLD1 promoter provides an attractive alternative for expression of foreign genes besides the commonly used alcohol oxidase promoter. The sequence has been deposited in the GenBank/NCBI data library under Accession No. AF364077.

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Section: Resultsmentioning

confidence: 99%

Molecular characterization of the Hansenula polymorphaFLD1 gene encoding formaldehyde dehydrogenase

Baerends

Sulter

Jeffries

et al. 2001

Yeast

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“…The class III ADH, showing no dismutase activity, is the ADH that in many other respects shows different properties from the other ADH forms. This ADH cannot be saturated with ethanol and it is the only ADH with glutathione-dependent formaldehyde dehydrogenase activity [22]. Furthermore, this ADH has been shown to be the origin of the zinc-dependent ADH enzymes [23].…”

Section: Discussionmentioning

confidence: 99%

Aldehyde dismutase activity of human liver alcohol dehydrogenase

et al. 1996

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Human alcohol dehydrogenases of class I and class II but not class III catalyse NAD+-dependent aldehyde oxidation in addition to the NADH-dependent aldehyde reduction. The two reactions are coupled, i.e. the enzymes display dismutase activity. Dismutase activity of recombinantly expressed human class I isozymes [~1[~1 and T2T2, class II and class III alcohol dehydrogenases was assayed with butanal as snbstrate by gas chromatographic-mass spectrometric quantitations of butanol and butyric acid. The class I Y2Y2 isozyme showed a pronounced dismutase activity with a high kcat, 1300 min -1, and a moderate Km, 1.2 mM. The class I ~1111 isozyme and the class II alcohol dehydrogenase showed moderate catalytic efficiencies for dismutase activity with lower kcat values, 60-75 min -1. 4-Methylpyrazole, a potent class I ADH inhibitor, inhibited the class I dismutation completely, but cyanamide, an inhibitor of mitochondrial aldehyde dehydrogenase, did not affect the dismutation. The dismutase reaction might be important for metabolism of aldehydes during inhibition or lack of mitochondrial aldehyde dehydrogenase activity.

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“…No semicarbazide was added to these wells, since it reacts with aldehydes, thus inhibiting the production of NADH. These specific substrate concentrations have been shown to saturate class III enzymes (19). The reactions were carried out for 10 min at 28°C to match the normal zebrafish environmental temperature.…”

Section: Methodsmentioning

confidence: 99%

“…Class III ADH (ADH5), also known as glutathione-dependent formaldehyde dehydrogenase (reviewed in Refs. 19 -21), preferentially metabolize longer chain aliphatic (longer than butanol) and aromatic alcohols; these activities are not inhibited by pyrazole derivatives (19). Class III enzymes cannot be saturated by ethanol (reviewed in Refs.…”

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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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Evidence for the identity of glutathione‐dependent formaldehyde dehydrogenase and class III alcohol dehydrogenase

Cited by 316 publications

References 18 publications

Molecular characterization of the Hansenula polymorphaFLD1 gene encoding formaldehyde dehydrogenase

Molecular characterization of the Hansenula polymorphaFLD1 gene encoding formaldehyde dehydrogenase

Aldehyde dismutase activity of human liver alcohol dehydrogenase

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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