Human hepatic cortisol reductase activities: enzymatic properties and substrate specificities of cytosolic cortisol Δ4-5β-reductase and dihydrocortisol-3α-oxidoreductase(s)
Abstract
The metabolism of cortisol by human liver homogenates has been studied. Cortisol delta 4-reductase and dihydrocortisol-3-oxidoreductase activities were distributed in all subcellular fractions. The products of the soluble enzymes were identified. Cortisol and 5 beta-dihydrocortisol were reduced to 3 alpha,5 beta-tetrahydrocortisol, and 5 alpha-dihydrocortisol was reduced to 3 alpha,5 alpha-tetrahydrocortisol. The soluble enzymes showed a wide range of substrate specificity. The 21 substituted cortisol derivatives were not metabolized. The apparent Km values of cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase for their substrates (cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol) all ranged from 18 to 27 microM. Dexamethasone inhibited the reduction of all of these substrates and the inhibition was abolished by 21 substitution of the dexamethasone. Testosterone was a competitive inhibitor of the reduction of cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol with a Ki ranging from 11 to 32 microM. NADPH was the preferred cofactor for the cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase. No end product inhibition was observed.
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AKR1D1 is expressed mainly in liver, consistent with its role in bile acid biosynthesis.
“AKR1D1 is expressed mainly in liver as might be expected by its role in bile acid biosynthesis”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [25]
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Rapid turnover of corticosterone in humans: the role of a second glucocorticoid hormonePreprint
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- Authors
- Iyer, R. B., Binstock, J. M., Schwartz, I. S., Gordon, G. G., Weinstein, B. I., & Southren, A. L.
- Affiliations
- New York Medical College (US)
- Corresponding author
- Southren, A.Louis
- Venue
- Steroids
- Publisher
- Elsevier BV
- Published
- 1990-11
- Volume
- 55
- Issue
- 11
- Pages
- 495-500
- ISSN
- 0039-128X (ISSN-L)
- OpenAlex
- W2040990615
- Cited by
- 21
- References
- 38
- Citations by year
- 2026: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2014: 1 · 2013: 1
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Steroids (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01ey001313-17a1)
- National Eye Institute (EY01313)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- cortisol metabolism, hepatic steroid metabolism, tetrahydrocortisol, substrate specificity, enzyme kinetics, NADPH cofactor, liver subcellular fractions
- MeSH terms
- Chromatography, High Pressure Liquid, Cytosol, Humans, Hydroxysteroid Dehydrogenases, Kinetics, Liver, Oxidoreductases, Spectrophotometry, Subcellular Fractions, Substrate Specificity, Testosterone, Tritium
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