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胆酸 7α-脱羟途径:历史、生化和微生物学。

The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation: history, biochemistry, and microbiology.

机构信息

Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL, USA; Center for Advanced Study, University of Illinois Urbana-Champaign, Urbana, IL, USA; Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.

Department of Biological Sciences, Eastern Illinois University, Charleston, IL, USA.

出版信息

J Lipid Res. 2023 Aug;64(8):100392. doi: 10.1016/j.jlr.2023.100392. Epub 2023 May 19.


DOI:10.1016/j.jlr.2023.100392
PMID:37211250
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10382948/
Abstract

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.

摘要

胆汁酸是源自胆固醇的清洁剂,其功能是溶解膳食脂质、从体内清除胆固醇,并作为营养信号分子在许多组织中发挥作用,其中肝脏和肠道的功能最为人所了解。20 世纪初的研究确立了胆汁酸的结构,到本世纪中叶,应用肠道微生物组学将肠道微生物组学应用于胆汁酸,使得区分宿主来源的“初级”胆汁酸和由宿主相关微生物群产生的“次级”胆汁酸成为可能。1960 年,在啮齿动物模型中的放射性标记研究导致确定了胆汁酸 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 Clostridium scindens VPI 12708 的细胞提取物进行的研究表明,胆汁酸 7-脱羟化是一个多步骤、分叉途径的结果,我们称之为 Hylemon-Björkhem 途径。由于疏水性次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产生它们的微生物 bai 基因,了解它们的起源非常重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/4b010fc9dc04/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/38541fcaf704/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/2f61ef7c3fbc/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/a3b2ce7f4375/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/c9a117ad25ff/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/a4cfebcfc2bd/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/f16d8721cbd9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/4639b72774e8/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/4eec2069717b/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/4b010fc9dc04/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/38541fcaf704/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/2f61ef7c3fbc/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/a3b2ce7f4375/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/c9a117ad25ff/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/a4cfebcfc2bd/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/f16d8721cbd9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/4639b72774e8/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/4eec2069717b/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/082c/10382948/4b010fc9dc04/gr9.jpg

相似文献

[1]
The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation: history, biochemistry, and microbiology.

J Lipid Res. 2023-8

[2]
Metabolism of Oxo-Bile Acids and Characterization of Recombinant 12α-Hydroxysteroid Dehydrogenases from Bile Acid 7α-Dehydroxylating Human Gut Bacteria.

Appl Environ Microbiol. 2018-5-1

[3]
Functional Intestinal Bile Acid 7α-Dehydroxylation by Associated with Protection from Infection in a Gnotobiotic Mouse Model.

Front Cell Infect Microbiol. 2016-12-20

[4]
Strain-dependent induction of primary bile acid 7-dehydroxylation by cholic acid.

BMC Microbiol. 2024-8-1

[5]
and characterization of bile acid transformations.

Gut Microbes. 2018-12-27

[6]
BaiJ and BaiB are key enzymes in the chenodeoxycholic acid 7α-dehydroxylation pathway in the gut microbe ATCC 35704.

Gut Microbes. 2024

[7]
Another renaissance for bile acid gastrointestinal microbiology.

Nat Rev Gastroenterol Hepatol. 2024-5

[8]
Isolation and characterization of a bile acid inducible 7alpha-dehydroxylating operon in Clostridium hylemonae TN271.

Anaerobe. 2009-5-21

[9]
Identification of a gene encoding a flavoprotein involved in bile acid metabolism by the human gut bacterium Clostridium scindens ATCC 35704.

Biochim Biophys Acta Mol Cell Biol Lipids. 2017-12-5

[10]
Identification and characterization of a bile acid 7alpha-dehydroxylation operon in Clostridium sp. strain TO-931, a highly active 7alpha-dehydroxylating strain isolated from human feces.

Appl Environ Microbiol. 2000-3

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