20alpha-hydroxysteroid dehydrogenase
In enzymology, a 20-α-hydroxysteroid dehydrogenase (EC 1.1.1.149) is an enzyme that catalyzes the chemical reaction
- 17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+ 17alpha-hydroxyprogesterone + NAD(P)H + H+
| 20-α-hydroxysteroid dehydrogenase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 1.1.1.149 | ||||||||
| CAS number | 9040-08-8 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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The 3 substrates of this enzyme are 17alpha,20alpha-dihydroxypregn-4-en-3-one, NAD+, and NADP+, whereas its 4 products are 17-alpha-hydroxyprogesterone, NADH, NADPH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 20alpha-hydroxysteroid:NAD(P)+ 20-oxidoreductase. Other names in common use include 20alpha-hydroxy steroid dehydrogenase, 20alpha-hydroxy steroid dehydrogenase, 20alpha-HSD, and 20alpha-HSDH. This enzyme participates in c21-steroid hormone metabolism.
20alpha-HSD has been initially described as a progesterone metabolizing enzyme of the ovary. On a functional level, ovarian 20alpha-HSD is actively involved in the control of progesterone homeostasis in pregnancy of rats and mice. While 20alpha-HSD expression and activity is downregulated in the corpus luteum of pregnancy, 24 hrs prior to parturition ovarian 20alpha-HSD activity is acutely stimulated. Accordingly, in mice with targeted deletion of the 20alpha-HSD gene, progesterone blood concentration remain high throughout pregnancy which results in a delay of 2–4 days in parturition. Indicating that expression of 20alpha-HSD activity is mandatory for the induction of parturition through reduction of progesterone blood concentration. In mice, 20alpha-HSD is also expressed in the adrenals, kidneys, brain, thymus, T cells and bone marrow. Its induction in hematopoietic cells was used as an assay for the identification of T cell derived factor interleukin-3. In addition, the enzyme reduces and inactivates 17-deoxycorticosterone, the precursor of aldosterone and corticosterone.
Structural studies
As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes 1MRQ (AKR1C1), 1Q13, and 1Q5M.
AKR1C1, AKR1C2, and AKR1C3
Enzymes
AKR1C1 has high catalytic efficiency as a 20α-HSD and AKR1C2 and AKR1C3 efficiently catalyze this reaction as well.[1]
References
- Byrns MC (January 2014). "Regulation of progesterone signaling during pregnancy: implications for the use of progestins for the prevention of preterm birth". J. Steroid Biochem. Mol. Biol. 139: 173–81. doi:10.1016/j.jsbmb.2013.01.015. PMID 23410596. S2CID 23414730.
Further reading
- Shikita M, Inano H, Tamaoki B (1967). "Further studies on 20-alpha-hydroxysteroid dehydrogenase of rat testes". Biochemistry. 6 (6): 1760–4. doi:10.1021/bi00858a026. PMID 4382486.
- Strickler RC, Tobias B, Covey DF (1981). "Human placental 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase. Two activities at a single enzyme active site". J. Biol. Chem. 256 (1): 316–21. PMID 6935192.
- Wiest WG, Kidwell WR, Balogh K (April 1968). "Progesterone catabolism in the rat ovary: a regulatory mechanism for progestational potency during pregnancy". Endocrinology. 82 (4): 844–59. doi:10.1210/endo-82-4-844. PMID 5742200.
- Wiest WG (December 1968). "On the function of 20 alpha-hydroxypregn-4-en-3-one during parturition in the rat". Endocrinology. 83 (6): 1181–4. doi:10.1210/endo-83-6-1181. PMID 5721991.
- Piekorz RP, Gingras S, Hoffmeyer A, Ihle JN, Weinstein Y (February 2005). "Regulation of progesterone levels during pregnancy and parturition by signal transducer and activator of transcription 5 and 20alpha-hydroxysteroid dehydrogenase". Mol. Endocrinol. 19 (2): 431–40. doi:10.1210/me.2004-0302. PMID 15471942.
- Akinola LA, Poutanen M, Vihko R, Vihko P (July 1997). "Expression of 17beta-hydroxysteroid dehydrogenase type 1 and type 2, P450 aromatase, and 20alpha-hydroxysteroid dehydrogenase enzymes in immature, mature, and pregnant rats". Endocrinology. 138 (7): 2886–92. doi:10.1210/en.138.7.2886. PMID 9202232.
- Weinstein Y (October 1977). "20alpha-hydroxysteroid dehydrogenase: a T lymphocyte-associated enzyme". J. Immunol. 119 (4): 1223–9. PMID 302277.
- Weinstein Y, Lindner HR, Eckstein B (April 1977). "Thymus metabolises progesterone- possible enzymatic marker for T lymphocytes". Nature. 266 (5603): 632–3. Bibcode:1977Natur.266..632W. doi:10.1038/266632a0. PMID 300849. S2CID 4146146.
- Ihle JN, Keller J, Oroszlan S, Henderson LE, Copeland TD, Fitch F, Prystowsky MB, Goldwasser E, Schrader JW, Palaszynski E, Dy M, Lebel B (July 1983). "Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity". J. Immunol. 131 (1): 282–7. PMID 6190911.
- Hershkovitz L, Beuschlein F, Klammer S, Krup M, Weinstein Y (March 2007). "Adrenal 20alpha-hydroxysteroid dehydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone". Endocrinology. 148 (3): 976–88. doi:10.1210/en.2006-1100. PMID 17122075.