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Cited by 139Steroid Chemistry and BiochemistryCholesterol and Lipid MetabolismAldose Reductase and Taurine

The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index.

Cloning and expression of cDNA of human Δ4‐3‐oxosteroid 5β‐reductase and substrate specificity of the expressed enzyme

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KONDO, Kazu‐Hiro, KAI, Masa‐Hiro, SETOGUCHI, Yoshiko, EGGERTSEN, Gösta, SJÖBLOM, Peter, SETOGUCHI, Toshiaki, OKUDA, Kyu‐Ichiro, BJÖRKHEM, Ingemar·1994·European Journal of Biochemistry
DOI 10.1111/j.1432-1033.1994.tb19947.x
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Abstract

The enzyme delta 4-3-oxosteroid 5 beta-reductase (3-oxo-5 beta-steroid: NADP+ oxidoreductase and 4,5 beta-dihydrocortisone: NADP+ delta 4-oxidoreductase) catalyzes the reduction of the delta 4 double bond of bile acid intermediates and steroid hormones carrying the delta 4-3-one structure in the A/B cis configuration. Human delta 4-3-oxosteroid 5 beta-reductase cDNA was isolated from a liver cDNA library by cross hybridization with a previously cloned rat cDNA, which was used as a probe [Onishi, Y. Noshiro, M., Shimosato, T. & Okuda, K.-I. (1991) FEBS Lett. 283, 215-218]. DNA sequence analysis of a hybridization-positive clone predicted the human delta 4-3-oxosteroid 5 beta-reductase to contain 326 amino acids. The amino acid sequence of the human delta 4-3-oxosteroid 5 beta-reductase had 79% overall identity to the rat enzyme sequence. It also showed 54% and 50% overall identity with rat 3 alpha-hydroxysteroid dehydrogenase and human aldose reductase, respectively. RNA blotting analysis demonstrated the existence of a single delta 4-3-oxosteroid 5 beta-reductase mRNA of approximately 2.7 kb in human liver. Transfection of the cDNA into COS cells resulted in the expression of an active enzyme with a high activity toward the bile acid intermediates 7 alpha,12 alpha-dihydroxy-4-cholesten-3-one and 7 alpha-hydroxy-4-cholesten-3-one. In addition, the expressed enzyme showed a small but significant 5 beta-reduction activity toward 11 beta,17 alpha,21-trihydroxy-delta 4-pregnene-3,20-dione (cortisol) and 17 beta-hydroxy-delta 4-androsten-3-one (testosterone) whereas no activity was observed toward delta 4-pregnene-3,20-dione (progesterone) or delta 4-androstene-3-17-dione (androstenedione). The substrate specificity of the human enzyme is considerably narrower than that of the rat enzyme, and the enzyme seems to be more important for bile acid biosynthesis than for metabolism of steroid hormones.

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Metadata

Authors
KONDO, K., KAI, M., SETOGUCHI, Y., EGGERTSEN, G., SJÖBLOM, P., SETOGUCHI, T., OKUDA, K., & BJÖRKHEM, I.
Affiliations
  • Karolinska Institutet (SE)
  • University of Miyazaki (JP)
Corresponding author
KONDO, Kazu‐Hiro
ORCID
Venue
European Journal of Biochemistry
Publisher
Wiley
Published
1994-01
Volume
219
Issue
1-2
Pages
357-363
ISSN
  • 0014-2956 (ISSN-L)
  • 1432-1033
DOI
10.1111/j.1432-1033.1994.tb19947.x
OpenAlex
W1985481419
Cited by
139
References
36
Citations by year
2025: 3 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 3 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 7
FWCI
1.52
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 4079 d)
Locations
  • European Journal of Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
Keywords
human cDNA cloning, substrate specificity, bile acid intermediates, 3α-hydroxysteroid dehydrogenase, aldose reductase, liver mRNA, recombinant enzyme expression, cortisol reduction, testosterone suppression
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cloning, Molecular, Escherichia coli, Humans, Liver, Molecular Sequence Data, Oxidoreductases, Recombinant Proteins, RNA, Substrate Specificity, Transfection, Immunoblotting, Restriction Mapping, Gene Expression, Sequence Homology, Amino Acid, DNA, Complementary, Rats

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