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  • Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis [Elektronski vir]
    Ačimovič, Jure ...
    Cholesterol synthesis is among the oldest metabolic pathways, consisting of the Bloch and Kandutch-Russell branches. Following lanosterol, sterols of both branches are proposed to be dedicated to ... cholesterol. We challenge this dogma by mathematical modeling and with experimental evidence. It was not possible to explain the sterol profile of testis in cAMP responsive element modulator tau (Crem [tau]) knockout mice with mathematical models based on textbook pathways of cholesterol synthesis. Our model differs in the inclusion of virtual sterol metabolizing enzymes branching from the pathway. We tested the hypothesis that enzymes from the cytochrome P450 (CYP) superfamily can participate in the catalysis of non-classical reactions. We show that CYP enzymes can metabolize multiple sterols in vitro, establishing novel branching points of cholesterol synthesis. In conclusion, sterols of cholesterol synthesis can be oxidized further to metabolites not dedicated to production of cholesterol. Additionally, CYP7A1, CYP11A1, CYP27A1, and CYP46A1 are parts of a broader cholesterol synthesis network.
    Source: Scientific reports [Elektronski vir]. - ISSN 2045-2322 (Vol. 6, Jun. 2016, str. 1-15)
    Type of material - e-article
    Publish date - 2016
    Language - english
    COBISS.SI-ID - 32717273

    Link(s):

    http://www.nature.com/articles/srep28462
    DOI

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