Inactivity of human β,β-carotene-9′, 10-′dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment

Update item information
Publication Type pre-print
School or College School of Medicine
Department Ophthalmology
Creator Frederick, Jeanne M.
Other Author Li, Binxing; Vachali, Preejith P.; Gorusupudi, Aruna; Shen, Zhengquing; Sharifzadeh, Hassan; Besch, Brian M.; Nelson, Kelly; Horvath, Madeleine M.; Baehr, Wolfgang, Bernstein, Paul S.
Title Inactivity of human β,β-carotene-9′, 10-′dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment
Date 2014-01-01
Description The macula of the primate retina uniquely concentrates high amounts of the xanthophyll carotenoids lutein, zeaxanthin, and meso-zeaxanthin, but the underlying biochemical mechanisms for this spatial- and species-specific localization have not been fully elucidated. For example, despite abundant retinal levels in mice and primates of a binding protein for zeaxanthin and mesozeaxanthin, the pi-isoform of glutathione S-transferase (GSTP1), only human and monkey retinas naturally contain detectable levels of these carotenoids. We therefore investigated whether or not differences in expression, localization, and activity between mouse and primate carotenoid metabolic enzymes could account for this species-specific difference in retinal accumulation. We focused on β,β-carotene-9',10'-dioxygenase (BCO2; also known as BCDO2), the only known mammalian xanthophyll cleavage enzyme. RT-PCR, western blot analysis, and immunohistochemistry confirmed that BCO2 is expressed in both mouse and primate retinas. Cotransfection of expression plasmids of human or mouse BCO2 into E. coli strains engineered to produce zeaxanthin demonstrated that only mouse BCO2 is an active zeaxanthin cleavage enzyme. Surface plasmon resonance (SPR) binding studies showed that the binding affinities between human BCO2 and lutein, zeaxanthin, and meso-zeaxanthin are 10- to 40-fold weaker than those for mouse BCO2, implying that ineffective capture of carotenoids by human BCO2 prevents cleavage of xanthophyll carotenoids. Moreover, BCO2 knockout mice, unlike wild-type mice, accumulate zeaxanthin in their retinas. Our results provide a novel explanation for how primates uniquely concentrate xanthophyll carotenoids at high levels in retinal tissue.
Type Text
Publisher National Academy of Sciences
Volume 111
Issue 28
First Page 10173
Last Page 10178
Language eng
Bibliographic Citation Li, B., Vachali, P. P., Gorusupudi, A., Shen, Z., Sharifzadeh, H., Besch, B. M., Nelson, K., Horvath, M. M., Frederick, J. M., Baehr, W., & Bernstein, P. S. (2014). Inactivity of human β,β-carotene-9′, 10-′dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment. Proceedings of the National Academy of Sciences of the United States of America, 111(28), 10173-8.
Rights Management (c) National Academy of Sciences ; www.pnas.org/cgi/doi/10.1073/pnas.1402526111
Format Medium application/pdf
Format Extent 3,676,917 bytes
Identifier uspace,18824
ARK ark:/87278/s62n8bcs
Setname ir_uspace
Date Created 2014-08-15
Date Modified 2021-05-06
ID 712641
Reference URL https://collections.lib.utah.edu/ark:/87278/s62n8bcs