Swansea University Medical School, UK.
FEBS J. 2021 Jun;288(12):3727-3745. doi: 10.1111/febs.15727. Epub 2021 Feb 17.
Every cell in vertebrates possesses the machinery to synthesise cholesterol and to metabolise it. The major route of cholesterol metabolism is conversion to bile acids. Bile acids themselves are interesting molecules being ligands to nuclear and G protein-coupled receptors, but perhaps the intermediates in the bile acid biosynthesis pathways are even more interesting and equally important. Here, we discuss the biological activity of the different intermediates generated in the various bile acid biosynthesis pathways. We put forward the hypothesis that the acidic pathway of bile acid biosynthesis has primary evolved to generate signalling molecules and its utilisation by hepatocytes provides an added bonus of producing bile acids to aid absorption of lipids in the intestine.
脊椎动物的每个细胞都拥有合成胆固醇和代谢胆固醇的机制。胆固醇代谢的主要途径是转化为胆汁酸。胆汁酸本身就是有趣的分子,它们是核受体和 G 蛋白偶联受体的配体,但也许胆汁酸生物合成途径中的中间产物更有趣,同样重要。在这里,我们讨论了不同胆汁酸生物合成途径中产生的不同中间产物的生物学活性。我们提出了这样的假设,即胆汁酸生物合成的酸性途径主要是为了产生信号分子,而其被肝细胞利用为吸收肠内脂质提供了胆汁酸的额外好处。