1. Characterization of the Role of β-Carotene 9,10-Dioxygenase in Macular Pigment Metabolism
- Author
-
Marcin Golczak, M. Airanthi K. Widjaja-Adhi, Johannes von Lintig, Darwin Babino, Grzegorz Palczewski, and Philip D. Kiser
- Subjects
Models, Molecular ,Oxygenase ,Protein Conformation ,Detergents ,Molecular Sequence Data ,Oxidative phosphorylation ,Mitochondrion ,medicine.disease_cause ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Dioxygenases ,Gene Knockout Techniques ,Mice ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Carotenoid ,chemistry.chemical_classification ,biology ,Carotenoid oxygenase ,food and beverages ,Hep G2 Cells ,Cell Biology ,Carotenoids ,Lipids ,Oxidative Stress ,Enzyme ,chemistry ,Xanthophyll ,biology.protein ,Cattle ,Female ,Macular Pigment ,Oxidative stress - Abstract
A family of enzymes collectively referred to as carotenoid cleavage oxygenases is responsible for oxidative conversion of carotenoids into apocarotenoids, including retinoids (vitamin A and its derivatives). A member of this family, the β-carotene 9,10-dioxygenase (BCO2), converts xanthophylls to rosafluene and ionones. Animals deficient in BCO2 highlight the critical role of the enzyme in carotenoid clearance as accumulation of these compounds occur in tissues. Inactivation of the enzyme by a four-amino acid-long insertion has recently been proposed to underlie xanthophyll concentration in the macula of the primate retina. Here, we focused on comparing the properties of primate and murine BCO2s. We demonstrate that the enzymes display a conserved structural fold and subcellular localization. Low temperature expression and detergent choice significantly affected binding and turnover rates of the recombinant enzymes with various xanthophyll substrates, including the unique macula pigment meso-zeaxanthin. Mice with genetically disrupted carotenoid cleavage oxygenases displayed adipose tissue rather than eye-specific accumulation of supplemented carotenoids. Studies in a human hepatic cell line revealed that BCO2 is expressed as an oxidative stress-induced gene. Our studies provide evidence that the enzymatic function of BCO2 is conserved in primates and link regulation of BCO2 gene expression with oxidative stress that can be caused by excessive carotenoid supplementation.
- Published
- 2015
- Full Text
- View/download PDF