The interrelationships of alcohol dehydrogenase and the aldehyde dehydrogenases in the metabolism of ethanol in liver

Harrington, Michael; Henehan, Gary; Tipton, Keith F.

doi:10.1042/bst0160239

Cited by 9 publications

(3 citation statements)

References 3 publications

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“…ALDHs are a group of NADP-dependent enzymes that catalyze the conversion of aldehydes into acid metabolites. They also participate in the metabolism of alcohols [2], biogenic amines [3], vitamins [4], steroids [5] and lipids [6,7], as well as in the biotransformation of numerous drugs and environmental agents [8]. …”

Section: Introductionmentioning

confidence: 99%

Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression through the induction of GADD153–C/EBPβ interaction

Elizondo

Medina-Díaz

Cruz

et al. 2009

Biochemical Pharmacology

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Mammalian class I aldehyde dehydrogenase (ALDH) plays an important role in the biosynthesis of the hormone retinoic acid (RA), which modulates gene expression and cell differentiation. RA has been shown to mediate control of human ALDH1 gene expression through modulation of the retinoic acid receptor α (RARα) and the CCAAT/enhancer binding protein β (C/EBPβ). The positive activation of these transcription factors on the ALDH1 promoter is inhibited by RA through a decrease of C/EBPβ binding to the ALDH1 CCAAT box response element. However, the mechanism of this effect remains unknown. Here we report that the RARα/retinoid X receptor β (RXRβ) complex binds to the mouse retinaldehyde dehydrogenase 1 (Raldh1) promoter at a non-consensus RA response element (RARE) with similar affinity to that of the consensus RARE. We found that C/EBPβ binds to a Raldh1 CCAAT box located at -82/-58 bp, adjacent to the RARE. Treatment with RA increases GADD153 and GADD153-C/EBPβ interaction resulting in a decreased cellular availability of C/ EBPβ for binding to the Raldh1 CCAAT box. These data support a model in which high RA levels inhibit Raldh1 gene expression by sequestering C/EBPβ through its interaction to GADD153.

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Section: Introductionmentioning

confidence: 99%

Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression through the induction of GADD153–C/EBPβ interaction

Elizondo

Medina-Díaz

Cruz

et al. 2009

Biochemical Pharmacology

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“…The aldehyde dehydrogenases (ALDH) (EC 1.2.1.3) are a family of enzymes that catalyze the oxidation of a great number of aldehydes to their corresponding acids. The participation of different ALDH isozymes in the detoxification of acetaldehyde from ethanol ingestion [1], metabolism of corticosteroids [2], biogenic amines [3], neurotransmitters [4]and retinoic acid (RA) [5]has been reported.…”

Section: Introductionmentioning

confidence: 99%

The cytosolic aldehyde dehydrogenase gene (Aldh1) is developmentally expressed in Leydig cells

López-Fernández

Mazo

1997

FEBS Letters

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“…The most likely candidate for this role is aldehyde dehydrogenase. It has been suggested previously that the concentration of acetaldehyde is governed by a balance between the activities of alcohol dehydrogenase and aldehyde dehydrogenase (Eriksson et al, 1975;Braggins et al, 1980;Braggins & Crow, 1981;Dawson, 1981;Crow et al, 1982;Harrington et al, 1988). The steady-state concentration of acetaldehyde may vary widely as a result of small changes in the relative activities of these two enzymes.…”

Section: Discussionmentioning

confidence: 96%

The importance of alcohol dehydrogenase in regulation of ethanol metabolism in rat liver cells

Page

Kitson

Hardman

1991

Biochemical Journal

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We used titration with the inhibitors tetramethylene sulphoxide and isobutyramide to assess quantitatively the importance of alcohol dehydrogenase in regulation of ethanol oxidation in rat hepatocytes. In hepatocytes isolated from starved rats the apparent Flux Control Coefficient (calculated assuming a single-substrate irreversible reaction with non-competitive inhibition) of alcohol dehydrogenase is 0.3-0.5. Adjustment of this coefficient to allow for alcohol dehydrogenase being a two-substrate reversible enzyme increases the value by 1.3-1.4-fold. The final value of the Flux Control Coefficient of 0.5-0.7 indicates that alcohol dehydrogenase is a major rate-determining enzyme, but that other factors also have a regulatory role. In hepatocytes from fed rats the Flux Control Coefficient for alcohol dehydrogenase decreases with increasing acetaldehyde concentration. This suggests that, as acetaldehyde concentrations rise, control of the pathway shifts from alcohol dehydrogenase to other enzymes, particularly aldehyde dehydrogenase. There is not a single rate-determining step for the ethanol metabolism pathway and control is shared among several steps.

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The interrelationships of alcohol dehydrogenase and the aldehyde dehydrogenases in the metabolism of ethanol in liver

Cited by 9 publications

References 3 publications

Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression through the induction of GADD153–C/EBPβ interaction

Retinoic acid modulates retinaldehyde dehydrogenase 1 gene expression through the induction of GADD153–C/EBPβ interaction

The cytosolic aldehyde dehydrogenase gene (Aldh1) is developmentally expressed in Leydig cells

The importance of alcohol dehydrogenase in regulation of ethanol metabolism in rat liver cells

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