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Features of the retinal environment which affect the activities and product profile of cholesterol-metabolizing CYP27A1 and CYP11A1

Published

Author(s)

Illarion V. Turko, Gun-Young Heo, Wei-Li Liao, Irina A. Pikuleva

Abstract

The retina is the sensory organ in the back of the eye which absorbs and converts the light to electrochemical impulses transferred to the brain. Herein, we studied how retinal environment affects enzyme-mediated cholesterol removal. We focused on two mitochondrial cytochrome P450 enzymes, CYPs 27A1 and 11A1, which catalyze the first steps in metabolism of cholesterol in the retina and other tissues. Phospholipids (PL) from mitochondria of bovine neural retina, retinal pigment epithelium, liver and adrenal cortex were isolated and compared for the effect on kinetic properties of purified recombinant CYPs in the reconstituted system in vitro. The four studied tissues were also evaluated for the mitochondrial PL and cholesterol content and levels of CYPs 27A1, 11A1 and their redox partners. The data obtained were used for modeling the retinal environment in the in vitro enzyme assays in which we detected the P450 metabolites, 22R-hydroxycholesterol and 5-cholestenoic acid, unexpectedly found by us in the retina in our previous studies. The effect of the by-product of the visual cycle pyridinium bis-retinoid A2E on kinetics of CYP27A1-mediated cholesterol metabolism was also investigated. The results provide insight into the retina’s regulation of the enzyme-mediated cholesterol removal.
Citation
Archives of Biochemistry and Biophysics
Volume
518
Issue
2

Keywords

cholesterol, 5-cholestenoic acid, 22R-hydroxycholesterol, phospholipids, ferredoxin, ferredoxin reductase, CYP46A1, A2E.

Citation

Turko, I. , Heo, G. , Liao, W. and Pikuleva, I. (2012), Features of the retinal environment which affect the activities and product profile of cholesterol-metabolizing CYP27A1 and CYP11A1, Archives of Biochemistry and Biophysics, [online], https://doi.org/10.1016/j.abb.2011.12.016 (Accessed April 14, 2024)
Created February 15, 2012, Updated November 10, 2018