The DOI matches its Crossref record; 168 of the 171 references it cites were found in a registry or an index.
Structural and functional biology of aldo-keto reductase steroid transforming enzymes
Open accessAbstract
Aldo-keto reductases (AKRs) are monomeric NAD(P)(H)-dependent oxidoreductases that play pivotal roles in the biosynthesis and metabolism of steroids in humans. AKR1C enzymes acting as 3-ketosteroid, 17-ketosteroid, and 20-ketosteroid reductases are involved in the prereceptor regulation of ligands for the androgen, estrogen, and progesterone receptors and are considered drug targets to treat steroid hormone-dependent malignancies and endocrine disorders. In contrast, AKR1D1 is the only known steroid 5β-reductase and is essential for bile-acid biosynthesis, the generation of ligands for the farnesoid X receptor, and the 5β-dihydrosteroids that have their own biological activity. In this review we discuss the crystal structures of these AKRs, their kinetic and catalytic mechanisms, AKR genomics (gene expression, splice variants, polymorphic variants, and inherited genetic deficiencies), distribution in steroid target tissues, roles in steroid hormone action and disease, and inhibitor design.
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In the citing paper
“More specifically, DHEA can be converted to A4 by peripheral HSD3B1, with A4 serving as the substrate for the production of testosterone by AKR1C3 [54].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [54]
In the citing paper
“Those androgens and precursors that escape the tissue specific activation via 5α-reduction are metabolized within the liver, which expresses both 5α- and 5β-reductases [54,94,100].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [54]
In the citing paper
“Following 5α/5β-reduction, androgen metabolites are subject to reduction of the 3-keto group with predominant 3α-stereoselectivity [54].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [54]
In the citing paper
“Even 5β-DHT, the product of the 5β-reduction of testosterone, is an inactive androgen metabolite [54].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [54]
Citations
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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
“precursors that escape the tissue specific activation via 5α-reduction are metabolized within the liver, which expresses both 5α- and 5β-reductases [54,94,100].”
Influential11-Oxygenated androgens in health and disease
Turcu, A. F., Rege, J., Auchus, R. J., & Rainey, W. E. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0336-x · Cited by 217
Self-citationThe Biosynthesis of Enzymatically Oxidized Lipids
Hajeyah, A. A., Griffiths, W. J., Wang, Y., Finch, A. J., & O’Donnell, V. B. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.591819 · Cited by 198
Aldo-Keto Reductases and Cancer Drug Resistance
Penning, T. M., Jonnalagadda, S. K., Trippier, P. C., & Rižner, T. L. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000122 · Cited by 158
Self-citationMicrobial Hydroxysteroid Dehydrogenases: From Alpha to Omega
Doden, H. L., & Ridlon, J. M. (2021) · Microorganisms · doi:10.3390/microorganisms9030469 · Cited by 113
Metadata
- Authors
- Penning, T. M., Wangtrakuldee, P., & Auchus, R. J.
- Affiliations
- University of Pennsylvania (US)
- University of Michigan (US)
- Corresponding author
- Penning, Trevor M
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2018-08-20
- Volume
- 40
- Issue
- 2
- Pages
- 447-475
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC6405412
- OpenAlex
- W2888187525
- Cited by
- 164
- References
- 171
- Citations by year
- 2026: 30 · 2025: 28 · 2024: 34 · 2023: 27 · 2022: 19 · 2021: 16 · 2020: 7 · 2019: 3
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrine Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Environmental Health Sciences (P30 ES013508)
- National Institute of General Medical Sciences (R01GM086596)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- aldo-keto reductase, AKR1D1, steroid metabolism, androgen receptor, estrogen receptor, progesterone receptor, bile acid synthesis, farnesoid X receptor, enzyme crystal structure, catalytic mechanism, enzyme kinetics, splice variants, genetic polymorphism, enzyme inhibitors, endocrine disorders
- MeSH terms
- Aldo-Keto Reductases, Humans, Hydroxysteroid Dehydrogenases, Oxidoreductases, Steroids
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