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Review
. 2021 Feb 24;9(3):469.
doi: 10.3390/microorganisms9030469.

VSports - Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega

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Review

VSports在线直播 - Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega

"VSports手机版" Heidi L Doden et al. Microorganisms. .

Abstract

Bile acids (BAs) and glucocorticoids are steroid hormones derived from cholesterol that are important signaling molecules in humans and other vertebrates VSports手机版. 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. .

Keywords: androgen; bile acid; cholesterol; cortisol; deoxycholic acid; hydroxysteroid dehydrogenase; sterolbiome. V体育安卓版.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Steroid structure. Steroids have a cyclopentanoperhydrophenanthrene ring structure. Cholesterol, the precursor to human steroid hormones, contains 27 carbons, while the major classes of steroid hormones contain the following: C24 bile acids, C19 androgens, C18 estrogens, and C21 glucocorticoids, mineralocorticoids, and progestogens.
Figure 2
Figure 2
Synthesis and microbial metabolism of bile acids and cortisol. (1) The bile acids (BAs) cholic acid (CA) and chenodeoxycholic acid (CDCA) are synthesized and conjugated to glycine (Gly) or taurine (Tau) in the liver. (2) They are then stored in the gallbladder until they are released in response to a meal. (3) Microbial deconjugation of amino acids, catalyzed by bile salt hydrolase (BSH), primarily occurs in the small intestine. (4) BAs are taken up in the terminal ileum and undergo enterohepatic circulation back to the liver indicated by green arrows. (5) About 5% of BAs are not recycled and proceed to the colon. (6) Gut microbiota residing in the colon can 7α-dehydroxylate CA or CDCA to secondary BAs in a pathway encoded by the BA-inducible (bai) operon. Microbial hydroxysteroid dehydrogenases (HSDHs) interconvert BA hydroxyl groups between the α- and β-conformations through an oxo-intermediate. (A) Cortisol is synthesized in the adrenal glands. (B) Cortisol and its derivatives are principally excreted in urine; however, low levels are secreted in bile and enter the gut. (C) In the gut, cortisol can be side-chain cleaved by microbiota encoding steroid-17,20-desmolase (DesAB) or reduced to 20α- or 20β-dihydrocortisol by HSDHs.
Figure 3
Figure 3
Microbial bile acid hydroxysteroid dehydrogenase metabolism. After deconjugation by bile salt hydrolase, the primary bile acids (BAs) chenodeoxycholic acid (CDCA) and cholic acid (CA) can be 7α-dehydroxylated or reversibly biotransformed by NAD(P)(H)-dependent hydroxysteroid dehydrogenases (HSDHs). CDCA is converted to the oxo-intermediate, 7-oxolithocholic acid (7-oxoLCA), and further to ursoDCA (UDCA) in the urso-BA pathway catalyzed by 7α- and 7β-HSDH. The secondary BAs lithocholic acid (LCA) and deoxycholic acid (DCA) are produced through the multi-step 7α-dehydroxylation of CDCA and CA, respectively. 3α-HSDH biotransforms DCA into 3-oxoDCA, and 3β-HSDH converts 3-oxoDCA to isoDCA in the iso-BA pathway. DCA is converted to 12-oxoLCA by 12α-HSDH and from 12-oxoLCA to epiDCA by 12β-HSDH. HSDHs can recognize other BAs with the correct hydroxyl group position and orientation beyond those depicted.
Figure 4
Figure 4
Proposed model for the role of Eggerthella lenta hydroxysteroid dehydrogenases: bile acid oxidation provides reductant for the Wood–Ljundahl Pathway (WLP) of acetogenesis. This model is based on biochemical and genomic data demonstrating that E. lenta strains contain complete WLP genes, and that bile acid oxidation is inhibited by a hydrogen gas atmosphere.
Figure 5
Figure 5
Microbial cortisol hydroxysteroid dehydrogenase metabolism. Cortisol can be reversibly biotransformed by 20β-hydroxysteroid dehydrogenase (20β-HSDH; DesE) to 20β-dihydrocortisol, or by 20α-HSDH (DesC) to 20α-dihydrocortisol. Steroid-17,20-desmolase (DesAB) converts cortisol to 11β-hydroxyandrostenedione (11β-OHAD). 21-Dehydroxylase catalyzes conversion of cortisol to 21-deoxycortisol.

VSports - References

    1. Norman A.W., Henry H.L. Steroid Hormones: Chemistry, Biosynthesis, and Metabolism. In: Norman A.W., Henry H.L., editors. Hormones. Academic Press; London, UK: 2015. pp. 27–53.
    1. Litwack G. Steroid hormones. In: Litwack G., editor. Human Biochemistry. Academic Press; London, UK: 2018. pp. 467–506.
    1. Payne A.H., Hales D.B. Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr. Rev. 2004;25:947–970. doi: 10.1210/er.2003-0030. - DOI - PubMed
    1. Ridlon J.M., Harris S.C., Bhowmik S., Kang D.J., Hylemon P.B. Consequences of bile salt biotransformations by intestinal bacteria. Gut Microbes. 2016;7:22–39. doi: 10.1080/19490976.2015.1127483. - DOI - PMC - PubMed
    1. Penning T.M. Molecular endocrinology of hydroxysteroid dehydrogenases. Endocr. Rev. 1997;18:281–305. - PubMed

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