Cited by 55Steroid Chemistry and BiochemistryAldose Reductase and TaurineCholesterol and Lipid Metabolism

5β-Reduced steroids and human Δ4-3-ketosteroid 5β-reductase (AKR1D1)

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Chen, Mo, Penning, Trevor M.·2014·Steroids

Abstract

5β-Reduced steroids are non-planar steroids that have a 90° bend in their structure to create an A/B cis-ring junction. This novel property is required for bile-acids to act as emulsifiers, but in addition 5β-reduced steroids have remarkable physiology and may act as potent tocolytic agents, endogenous cardiac glycosides, neurosteroids, and can act as ligands for orphan and membrane bound receptors. In humans there is only a single 5β-reductase gene AKR1D1, which encodes Δ(4)-3-ketosteroid-5β-reductase (AKR1D1). This enzyme is a member of the aldo-keto reductase superfamily, but possesses an altered catalytic tetrad, in which Glu120 replaces the conserved His residue. This predominant liver enzyme generates all 5β-dihydrosteroids in the C19-C27 steroid series. Mutations exist in the AKR1D1 gene, which result in loss of protein stability and are causative in bile-acid deficiency.

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Authors
Chen, M., & Penning, T. M.
Affiliations
University of Pennsylvania (US)
Corresponding author
Penning, Trevor M.
Venue
Steroids
Publisher
Elsevier BV
Published
2014-05
Volume
83
Pages
17-26
ISSN
0039-128X (ISSN-L)
OpenAlex
W2052427467
Cited by
55
References
138
Citations by year
2026: 5 · 2025: 7 · 2024: 8 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 6 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 1 · 2014: 3
FWCI
0.38
Type
journal article
Language
en
Open access
Locations
  • Steroids (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK47015, F32DK089827, R01DK047015)
  • National Institute of Environmental Health Sciences (P30ES13508, P30ES013508)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
AKR1D1, bile acids, aldo-keto reductase superfamily, tocolytic agents, endogenous cardiac glycosides, neurosteroids, orphan receptors, bile acid deficiency
MeSH terms
Humans, Oxidation-Reduction, Oxidoreductases, Steroids, Gene Expression Profiling

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