Elsevier

Biochemical Pharmacology

Volume 42, Issue 6, 22 August 1991, Pages 1279-1285
Biochemical Pharmacology

Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid

https://doi.org/10.1016/0006-2952(91)90266-8Get rights and content

Abstract

NAD(P)-linked aldehyde dehydrogenases catalyze the oxidation of a wide variety of aldehydes. Thirteen of these enzymes have been identified in mouse tissues; eleven are found in the liver. Some are substrate-nonspecific; others are relatively substrate-specific. The present investigation sought to determine which of these enzymes are operative in catalyzing the oxidation of retinaldehyde to retinoic acid, a metabolite of vitamin A that promotes the differentiation of epithelial and other cells. Spectrophotometric and HPLC assays were used for this purpose. Enzyme-catalyzed oxidation of retinaldehyde (25 μM) was restricted to the cytosol (105,000g supernatant fraction) and occurred at a rate of 211 nmol/min/g liver; oxidation of acetaldehyde (4 mM) by this fraction proceeds about ten times faster. At least 90% of this activity was NAD dependent. Of the approximately 10% that was apparently NAD independent, two-thirds was inhibited by 1 mM pyridoxal, a known inhibitor of aldehyde oxidase. Of the six cytosolic aldehyde dehydrogenases, only two, viz. AHD-2 and AHD-7, catalyzed the oxidation of retinaldehyde to retinoic acid. An additional NAD-dependent enzyme, viz. xanthine oxidase (dehydrogenase form), also catalyzed the reaction. Catalysis by AHD-2 accounted for more than 90% of the total NAD-dependent activity. Km values were 0.7, 0.6 and 0.9 μM, respectively, for the AHD-2-, AHD-7- and xanthine oxidase (dehydrogenase form)-catalyzed reaction. AHD-4, an aldehyde dehydrogenase found in the cytosol of mouse stomach epithelium and cornea, did not catalyze the reaction.

References (48)

  • MA Leo et al.

    Increased hepatic retinal dehydrogenase activity after phenobarbital and ethanol administration

    Biochem Pharmacol

    (1989)
  • JL Napoli et al.

    Microsomes convert retinol and retinal into retinoic acid and interfere in the conversions catalyzed by cytosol

    Biochim Biophys Acta

    (1990)
  • S Futterman

    Enzymatic oxidation of vitamin A aldehyde to vitamin A acid

    J Biol Chem

    (1962)
  • TD Elder et al.

    The oxidation of retinene (vitamin A1 aldehyde) to vitamin A acid by mammalian steroid-sensitive aldehyde dehydrogenase

    Biochim Biophys Acta

    (1962)
  • CL Manthey et al.

    Kinetic characterization of the catalysis of “activated” cyclophosphamide (4-hydroxycyclophosphamide/aldophosphamide) oxidation to carboxyphosphamide by mouse hepatic aldehyde dehydrogenases

    Biochem Pharmacol

    (1988)
  • MM Bradford

    A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding

    Anal Biochem

    (1976)
  • UK Rout et al.

    Isoelectric focusing studies of aldehyde dehydrogenases from mouse tissues: Variant phenotypes of liver, stomach and testes isozymes

    Comp Biochem Physiol

    (1985)
  • K Inoue et al.

    Purification and partial characterization of aldehyde dehydrogenase from human erythrocytes

    Biochim Biophys Acta

    (1979)
  • TA Krenitsky et al.

    A comparison of the specificities of xanthine oxidase and aldehyde oxidase

    Arch Biochem Biophys

    (1972)
  • TA Krenitsky et al.

    A comparison of the distribution and electron acceptor specificities of xanthine oxidase and aldehyde oxidase

    Comp Biochem Physiol

    (1974)
  • RS Holmes et al.

    Aldehyde dehydrogenases, aldehyde oxidase and xanthine oxidase from baboon tissues: Phenotyplc variability and subcellular distribution in liver and brain

    Alcohol

    (1986)
  • BE Domeyer et al.

    Metabolism of 4-hydroxycyclophosphamide/aldophosphamide in vitro

    Biochem Pharmacol

    (1980)
  • RA Deitrich et al.

    Induction of different rat liver supernatant aldehyde dehydrogenases by phenobarbital and tetrachloro-dibenzo-p-dioxin

    J Biol Chem

    (1977)
  • RA Deitrich et al.

    Induction of aldehyde dehydrogenases

    Biochem Pharmacol

    (1978)
  • Cited by (0)

    Supported by USPHS Grant CA 21737. A description of parts of this investigation has appeared in abstract form (Lee et al., FASEB J4: A659, 1990).

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