Xanthine oxidase catalyzes the oxidation of retinol

Abstract

In mammals, xanthine oxidase (E.C. 1.17.3.2) catalyzes the hydroxylation of a wide variety of heterocyclic substrates such as purines, pyrimidines, and pterins, in addition to aldehydes [] as all-trans-retinaldehyde . Here, we show that buttermilk xanthine oxidase was capable to oxidizing all-trans-retinol (t-ROL) to all-trans-retinaldehyde (t-RAL) that was successively oxidized to all-trans-retinoic acid (t-RA). A rise in the enzyme activity, when t-ROL-CRBP complex was assayed, with respect to the free t-ROL, was observed. Furthermore, treatment of the enzyme with Na₂S and glutathione resulted in a significant increment in catalytic activity toward t-ROL and t-RAL, due to the reconstitution of the native structural organization of the molybdenum centre of molybdopterin cofactor of the desulfo form of xanthine oxidase.

Keywords::

• Xanthine oxidase
• retinol oxidation
• retinaldehyde oxidation
• retinoic acid biosynthesis
• cellular retinoid binding protein (CRBP)
• Cellular retinoic acid binding protein (CRABP)
• retinol binding protein (RBP)

Acknowledgements

We wish to thank Prof. Luigi Castagnetta and Dr. Giuseppe Carruba for providing generous access to the Laboratory of Experimental Oncology Unit, Department of Clinical Oncology, ARNAS-Civico, Palermo. We also thank Dr. Letizia Cocciadiferro for help with the cell culture and Dr. Grazia M. Granata for radio chromatography analysis. This work was supported by a MURST grant.