Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega.
Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega.
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DOI：
10.3390/microorganisms9030469
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发表时间：
2021-02-24
期刊：
影响因子：
4.5
通讯作者：
Ridlon JM
中科院分区：
文献类型：
--
作者：
Doden HL;Ridlon JM
胆汁酸（BA）和糖皮质激素是衍生自胆固醇的类固醇激素，是人类和其他脊椎动物中重要的信号分子。羟基类固醇脱氢酶（HSDH）由宿主及其驻留的肠道微生物群编码，并且它们可逆地将类固醇羟基转化为酮基。对HSDH可以可逆地将类固醇从α-羟基构象差向异构化为β-羟基，或在ω-鼠胆酸的情况下将β-羟基差向异构化为ω-羟基。这些反应通常产生与其前体具有显著不同的物理化学性质的产物，这可导致类固醇成为宿主受体的激活剂或抑制剂，可影响粪便水中的溶解度，并可调节毒性。微生物的高密度脂蛋白脱氢酶调节与结肠直肠癌、肝癌、前列腺癌和多囊卵巢综合征等疾病相关的固醇。虽然微生物HSDPA的作用尚未完全阐明，但它们在未来可能具有作为类固醇库调节剂或药物靶点的治疗潜力。在这篇综述中，我们探讨代谢的BA和糖皮质激素的生物转化的微生物HSDPA的重点。
Bile acids (BAs) and glucocorticoids are steroid hormones derived from cholesterol that are important signaling molecules in humans and other vertebrates. Hydroxysteroid dehydrogenases (HSDHs) are encoded both by the host and by their resident gut microbiota, and they reversibly convert steroid hydroxyl groups to keto groups. Pairs of HSDHs can reversibly epimerize steroids from α-hydroxy conformations to β-hydroxy, or β-hydroxy to ω-hydroxy in the case of ω-muricholic acid. These reactions often result in products with drastically different physicochemical properties than their precursors, which can result in steroids being activators or inhibitors of host receptors, can affect solubility in fecal water, and can modulate toxicity. Microbial HSDHs modulate sterols associated with diseases such as colorectal cancer, liver cancer, prostate cancer, and polycystic ovary syndrome. Although the role of microbial HSDHs is not yet fully elucidated, they may have therapeutic potential as steroid pool modulators or druggable targets in the future. In this review, we explore metabolism of BAs and glucocorticoids with a focus on biotransformation by microbial HSDHs.
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影响因子：
6.5
作者：
Devendran, Saravanan;Mythen, Sean M.;Ridlon, Jason M.
通讯作者：
Ridlon, Jason M.
影响因子：
6.1
作者：
Bernstein, Carol;Holubec, Hana;Bhattacharyya, Achyut K.;Huy Nguyen;Payne, Claire M.;Zaitlin, Beryl;Bernstein, Harris
通讯作者：
Bernstein, Harris
影响因子：
29.4
作者：
Alemi F;Poole DP;Chiu J;Schoonjans K;Cattaruzza F;Grider JR;Bunnett NW;Corvera CU
通讯作者：
Corvera CU
影响因子：
4.4
作者：
BOKKENHEUSER, VD;WINTER, J;LOCASCIO, S
通讯作者：
LOCASCIO, S
影响因子：
5.8
作者：
Chiang JY
通讯作者：
Chiang JY