Regular Article
Two Different Enzymes Are Primarily Responsible for Retinoic Acid Synthesis in Rabbit Liver Cytosol

https://doi.org/10.1006/bbrc.1994.2803Get rights and content

Abstract

Retinoic acid biosynthesis in rabbit liver was catalyzed by cytosolic NAD+-dependent dehydrogenase and oxygen-dependent oxidase, with an activity ratio of 59% and 41% in the presence of 2 mM dithiothreitol under aerobic conditions. The two enzymes could be well separated by fractionation involving ammonium sulfate precipitation. Purification of the enzymes indicated that the oxygen-dependent enzyme was a flavoenzyme, retinal oxidase (EC 1.2.3.11), composed of two 135 kDa subunits; and the NAD+-dependent enzyme was a basic pI retinal dehydrogenase composed of four 55-kDa subunits. A high concentration (1-2 mM) of DTT was required to stabilize the activity of retinal dehydrogenase during the purification procedures and storage, but inhibited the activity of retinal oxidase by 13-38%. The physiological roles of the two retinoic acid synthases in liver cytosol were discussed.

References (0)

Cited by (45)

  • Critical overview on the structure and metabolism of human aldehyde oxidase and its role in pharmacokinetics

    2018, Coordination Chemistry Reviews
    Citation Excerpt :

    Similarly, tamoxifen (not in Table 3) is bio-transformed into an aldehyde intermediate by a monoamine oxidase, which is subsequently recognized and further metabolized by rat liver AOX enzymatic activity. Several potentially physiological relevant aldehydes that are substrates of AOX (reviewed in [4]) are 5-hydroxyindoleacetaldehyde, a serotonin oxidation metabolite, retinaldehyde [89–91] and pyridoxal, the dephosphorylated form of the active vitamin B6 metabolite [92,93]. Pyridoxal is an established substrate of aldehyde oxidases being of particular relevance in insects.

  • Xanthine Oxidoreductase and Aldehyde Oxidases

    2018, Comprehensive Toxicology: Third Edition
  • Pharmacological inhibition of ALDH1A in mice decreases all-trans retinoic acid concentrations in a tissue specific manner

    2015, Biochemical Pharmacology
    Citation Excerpt :

    In support of an enzyme other than an ALDH1A, WIN 18,446 only inhibited approximately 50% of the atRA formation by liver S10 protein. Previous work has demonstrated that AOX forms atRA from at-retinal [53] and contributes to approximately 50% of the atRA formation from at-retinal in the rabbit liver cytosol [54]. In agreement with this, the AOX inhibitor hydralazine inhibited approximately 50% of the mouse liver atRA formation suggesting a much greater importance of AOX in atRA formation in mice than previously suggested [30].

  • In vitro oxidation of aldehyde oxidase from rabbit liver: Specificity toward endogenous substrates

    2014, Journal of King Saud University - Science
    Citation Excerpt :

    Pyridoxal is currently the sole example of a substrate that shows a certain degree of selectivity for a specific aldehyde oxidase protein as it is not recognized by purified mouse (Terao et al., 2009). These findings are consistent with Huang and Ichikawa (1994) and Tsujita et al. (1994) who first observed the role of AO in the oxidation of all-trans-retinaldehyde to retinoic acid without NAD+ in rabbit by liver AO cytosol (Huang and Ichikawa, 1994; Tsujita et al., 1994). Km and Vmax values for the formation of 4-pyridoxic acid and retinoic acid metabolites, also determined spectrophotometrically as described in Methods, by rabbit enzyme fractions are tabulated in Table 3 and Figs. 3 and 4.

  • Effect of tea beverages on aldehyde oxidase activity

    2011, Drug Metabolism and Pharmacokinetics
View all citing articles on Scopus
View full text