title: Characterization of the Role of β-Carotene 9,10-Dioxygenase in Macular Pigment Metabolism.
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.
authors: From the Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 and.
authors: Darwin
authors: D
authors: Babino
authors: From the Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 and.
authors: Grzegorz
authors: G
authors: Palczewski
authors: From the Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 and.
authors: M Airanthi K
authors: MA
authors: Widjaja-Adhi
authors: From the Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 and the Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106.
authors: Philip D
authors: PD
authors: Kiser
authors: From the Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 and.
authors: Marcin
authors: M
authors: Golczak
authors: From the Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 and johannes.vonlintig@case.edu.
authors: Johannes
authors: J
authors: von Lintig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002338:Carotenoids / Q000378:metabolism; D002417:Cattle; D003902:Detergents / Q000494:pharmacology; D049308:Dioxygenases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D055786:Gene Knockout Techniques; D056945:Hep G2 Cells; D006801:Humans; D065348:Macular Pigment / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D011487:Protein Conformation
chemical_list: D003902:Detergents; D065348:Macular Pigment; D002338:Carotenoids; D049308:Dioxygenases; C506534:BCO2 protein, human; C481678:Bco2 protein, mouse
keywords: carotenoid; dioxygenase; enzyme; mitochondria; vision