Epimerase activity of the human 11β-hydroxysteroid dehydrogenase type 1 on 7-hydroxylated C19-steroids
Abstract
Cytochrome P4507B1 7alpha-hydroxylates dehydroepiandrosterone (DHEA), epiandrosterone (EpiA) and 5alpha-androstane-3beta,17beta-diol (Adiol). 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) interconverts 7alpha- and 7beta-forms. Whether the interconversion proceeds through oxido-reductive steps or epimerase activity was investigated. Experiments using [(3)H]-labelled 7beta-hydroxy-DHEA, 7beta-hydroxy-EpiA and 7beta-hydroxy-Adiol showed the (3)H-label to accumulate in the 7-oxo-DHEA trap but not in 7-oxo-EpiA or 7-oxo-Adiol traps. Computed models of 7-oxygenated steroids docked in the active site of 11beta-HSD1 either in a flipped or turned form relative to cortisone and cortisol. 7-Oxo-steroid reduction in 7alpha- or 7beta-hydroxylated derivatives resulted from either turned or flipped forms. 11beta-HSD1 incubation in H(2)(18)O medium with each 7-hydroxysteroid did not incorporate (18)O in 7-hydroxylated derivatives of EpiA and Adiol independently of the cofactor used. Thus oxido-reductive steps apply for the interconversion of 7alpha- and 7beta-hydroxy-DHEA through 7-oxo-DHEA. Epimerization may proceed on the 7-hydroxylated derivatives of EpiA and Adiol through a mechanism involving the cofactor and Ser(170). The physiopathological importance of this epimerization process is related to 7beta-hydroxy-EpiA production and its effects in triggering the resolution of inflammation.
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HSD11B1 functions as an epimerase interconverting the 7α- and 7β-hydroxy-stereoisomers via a 7-keto-intermediate.
“HSD11B1 functions as an epimerase interconverting the 7α- and 7β-hydroxy-stereoisomers via a 7-keto-intermediate”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [110]
HSD11B2 only oxidizes the 7α-hydroxy-stereoisomer.
“while HSD11B2 only oxidizes the 7α-hydroxy-stereoisomer [110,111].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [110]
Cites
Self-Consistent Equations Including Exchange and Correlation Effects
Kohn, W., & Sham, L. J. (1965) · Physical Review · doi:10.1103/physrev.140.a1133 · Cited by 64,135 · see citing works
Seckl, J. R., & Walker, B. R. (2001) · Endocrinology · doi:10.1210/endo.142.4.8114 · Cited by 714 · see citing works
Labrie, F., Luu-The, V., Labrie, C., & Simard, J. (2001) · Frontiers in Neuroendocrinology · doi:10.1006/frne.2001.0216 · Cited by 366 · see citing works
Wayman, N. S., Hattori, Y., McDonald, M. C., Mota‐Filipe, H., Cuzzocrea, S., PISANO, B., Chatterjee, P. K., & Thiemermann, C. (2002) · The FASEB Journal · doi:10.1096/fj.01-0793com · Cited by 361 · see citing works
Rajakariar, R., Hilliard, M., Lawrence, T., Trivedi, S., Colville‐Nash, P., Bellingan, G. J., Fitzgerald, D. J., Yaqoob, M., & Gilroy, D. W. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707394104 · Cited by 253 · see citing works
Rose, K. A., Stapleton, G., Dott, K., Kiény, M. P., Best, R., Schwarz, M., Russell, D. W., Björkhem, I., Seckl, J. R., & Lathe, R. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.4925 · Cited by 221 · see citing works
Seckl, J. R. (2001) · Endocrinology · doi:10.1210/en.142.4.1371 · Cited by 172 · see citing works
Identification and Characterization of a Mouse Oxysterol 7α-Hydroxylase cDNA
Schwarz, M., Lund, E. G., Lathe, R., Björkhem, I., & Russell, D. W. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23995 · Cited by 157 · see citing works
Seckl, J. R., & Walker, B. R. (2004) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2004.09.007 · Cited by 134 · see citing works
Rapid Hepatic Metabolism of 7-Ketocholesterol by 11β-Hydroxysteroid Dehydrogenase Type 1
Schweizer, R. A. S., Zürcher, M., Balázs, Z., Dick, B., & Odermatt, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313615200 · Cited by 131 · see citing works
Ou, Z., Zhao, X., Labiche, L. A., Strong, R., Grotta, J. C., Herrmann, O., & Aronowski, J. A. (2006) · Brain Research · doi:10.1016/j.brainres.2006.04.062 · Cited by 85 · see citing works
Hennebert, O., Chalbot, S., Alran, S., & Morfin, R. (2007) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2007.03.026 · Cited by 79 · see citing works
Self-citationMuller, C., Pompon, D., Urban, P., & Morfin, R. (2006) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2005.12.001 · Cited by 77 · see citing works
Self-citationComparative enzymology of 11β-hydroxysteroid dehydrogenase type 1 from six species
Arampatzis, S., Kadereit, B., Schuster, D., Balázs, Z., Schweizer, R. A. S., Frey, F. J., Langer, T., & Odermatt, A. (2005) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01736 · Cited by 76 · see citing works
Hult, G. T. M., Elleby, B., Shafqat, N., Svensson, S., Rane, A., J�rnvall, H., Abrahmsén, L., & Oppermann, U. C. T. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3476-y · Cited by 74 · see citing works
Abdelrahman, M., Collin, M., & Thiemermann, C. (2004) · Shock · doi:10.1097/01.shk.0000144132.13900.24 · Cited by 61 · see citing works
Khalil, M. W., Strutt, B. J., Vachon, D., & KILLINGER, D. W. (1993) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(93)90186-z · Cited by 49 · see citing works
Hennebert, O., Pélissier, M. A., Mée, S. L., Wülfert, E., & Morfin, R. F. (2008) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2007.12.014 · Cited by 43 · see citing works
Self-citationThe human cytochrome P4507B1: catalytic activity studies
Kim, S.-B., Chalbot, S., Pompon, D., Jo, D.-H., & Morfin, R. F. (2004) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2004.09.005 · Cited by 41 · see citing works
Self-citationChalbot, S., & Morfin, R. F. (2005) · Drug Metabolism and Disposition · doi:10.1124/dmd.104.003004 · Cited by 40 · see citing works
Self-citationHennebert, O., Pernelle, C., Ferroud, C., & Morfin, R. F. (2007) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2006.11.021 · Cited by 34 · see citing works
Self-citationMée, S. L., Hennebert, O., Ferrec, C., Wülfert, E., & Morfin, R. F. (2008) · Steroids · doi:10.1016/j.steroids.2008.05.001 · Cited by 33 · see citing works
Self-citationInhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 in Obesity
Wake, D. J., & Walker, B. R. (2006) · Endocrine · doi:10.1385/endo:29:1:101 · Cited by 32 · see citing works
Inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 for the treatment of metabolic syndrome.
Wang, M. (2006) · PubMed · Cited by 32 · see citing works
Resolving the problem of persistence in the switch from acute to chronic inflammation
Haworth, O., & Buckley, C. D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710633105 · Cited by 29 · see citing works
Trap, C., Nato, F., Chalbot, S., Kim, S.-B., Lafaye, P. J., & Morfin, R. F. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.09.019 · Cited by 22 · see citing works
Self-citationMiguet, L., Zhang, Z., Barbier, M., & Grigorov, M. (2006) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-006-9037-3 · Cited by 22 · see citing works
Neurosteroids: Metabolism in human intestine microsomes
Chalbot, S., & Morfin, R. F. (2005) · Steroids · doi:10.1016/j.steroids.2004.12.004 · Cited by 21 · see citing works
Self-citationIn vivo metabolism of 14C-labelled 5α-androstane-3β,17β-diol
Jacolot, F., Berthou, F., Dréano, Y., et al. (1981) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(81)90378-2 · Cited by 20 · see citing works
Type 1 11 β-hydroxysteroid Dehydrogenase as Universal Drug Target in Metabolic Diseases?
Oppermann, U. C. T. (2006) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/187153006778250000 · Cited by 19 · see citing works
Hennebert, O., LEMEE, S., Pernelle, C., & Morfin, R. F. (2007) · Steroids · doi:10.1016/j.steroids.2007.07.011 · Cited by 14 · see citing works
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Cited by
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Schiffer, L., Barnard, L., Baranowski, E. S., Gilligan, L. C., Taylor, A. E., Arlt, W., Shackleton, C. H. L., & Storbeck, K.-H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105439 · Cited by 450 · see citing works
Cutaneous glucocorticosteroidogenesis: securing local homeostasis and the skin integrity
Slominski, A. T., Manna, P. R., & Tuckey, R. C. (2014) · Experimental Dermatology · doi:10.1111/exd.12376 · Cited by 79 · see citing works
The origin of 7α-hydroxy-dehydroepiandrosterone and its physiological role: a history of discoveries
STÁRKA, L. (2017) · Physiological Research · doi:10.33549/physiolres.933717 · Cited by 8 · see citing works
- Authors
- Hennebert, O., Montes, M., Favre-Reguillon, A., Chermette, H., Ferroud, C., & Morfin, R.
- Affiliations
- Conservatoire National des Arts et Métiers (FR)
- Lyon 1 Université (FR)
- Corresponding author
- Morfin, Robert
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 114
- Issue
- 1-2
- Pages
- 57-63
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2043222718
- Cited by
- 27
- References
- 31
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- 11β-hydroxysteroid dehydrogenase type 1, epimerization, dehydroepiandrosterone, epiandrosterone, 5α-androstane-3β,17β-diol, inflammation resolution
- MeSH terms
- Cytochrome P450 Family 7, Androsterone, Dehydroepiandrosterone, Humans, Hydroxylation, Oxidation-Reduction, Steroid Hydroxylases, Steroids, Androstane-3,17-diol, Molecular Structure, Catalytic Domain, 11-beta-Hydroxysteroid Dehydrogenase Type 1
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