The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation: history, biochemistry, and microbiology.
The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation: history, biochemistry, and microbiology.
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胆汁酸7-去羟基化Hylemon-Björkhem途径：历史、生物化学和微生物学。
DOI：
10.1016/j.jlr.2023.100392
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发表时间：
2023-08
影响因子：
6.5
通讯作者：
Gaskins HR
中科院分区：
文献类型：
--
作者：
Ridlon JM;Daniel SL;Gaskins HR
胆汁酸是来源于胆固醇的去污剂，其功能是溶解膳食脂质，从体内去除胆固醇，并在许多组织中充当营养信号分子，其中肝脏和肠道中的功能是最好理解的。世纪早期的研究确立了胆汁酸的结构，到世纪中期，将微生物生物学应用于胆汁酸允许区分宿主来源的“初级”胆汁酸和由宿主相关微生物群产生的“次级”胆汁酸。1960年，在啮齿动物模型中进行的放射性标记研究确定了胆汁酸7-脱水反应的立体化学。提出了一个两步机制，我们称之为Samuelsson-Bergström模型，以解释脱氧胆酸的形成。随后对人类、啮齿动物和梭菌VPI 12708的细胞提取物进行的研究使我们认识到胆汁酸7-脱羟基化是一个多步分叉途径的结果，我们将其命名为Hylemon-Björkhem途径。由于疏水性二级胆汁酸的重要性，以及在粪便宏基因组研究中越来越多地测量编码产生它们的酶的微生物bai基因，因此了解它们的起源很重要。
Bile acids are detergents derived from cholesterol that function to solubilize dietary lipids, remove cholesterol from the body, and act as nutrient signaling molecules in numerous tissues with functions in the liver and gut being the best understood. Studies in the early 20th century established the structures of bile acids, and by mid-century, the application of gnotobiology to bile acids allowed differentiation of host-derived “primary” bile acids from “secondary” bile acids generated by host-associated microbiota. In 1960, radiolabeling studies in rodent models led to determination of the stereochemistry of the bile acid 7-dehydration reaction. A two-step mechanism was proposed, which we have termed the Samuelsson-Bergström model, to explain the formation of deoxycholic acid. Subsequent studies with humans, rodents, and cell extracts of Clostridium scindens VPI 12708 led to the realization that bile acid 7-dehydroxylation is a result of a multi-step, bifurcating pathway that we have named the Hylemon-Björkhem pathway. Due to the importance of hydrophobic secondary bile acids and the increasing measurement of microbial bai genes encoding the enzymes that produce them in stool metagenome studies, it is important to understand their origin.
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