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Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)
| steroid-5-alpha-reductase, alpha polypeptide 1 | |
|---|---|
| Symbol(s): | SRD5A1 |
| Locus: | 5 p15 |
| EC number | 1.3.99.5 |
| EntrezGene | 6715 |
| OMIM | 184753 |
| RefSeq | NM_001047 |
| UniProt | P18405 |
| steroid-5-alpha-reductase, alpha polypeptide 2 | |
|---|---|
| Symbol(s): | SRD5A2 |
| Locus: | 2 p23 |
| EC number | 1.3.99.5 |
| EntrezGene | 6716 |
| OMIM | 607306 |
| RefSeq | NM_000348 |
| UniProt | P31213 |
Steroidogenesis, showing both actions of 5-alpha reductase at bottom center.
5-Alpha reductases, also known as 3-oxo-5-alpha-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in 3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism, and prostate cancer.
5-Alpha reductases catalyze the following chemical reaction:
- a 3-oxo-5alpha-steroid + acceptor a 3-oxo-Delta4-steroid + reduced acceptor
Thus, the two substrates of these enzymes are an 3-oxo-5 alpha-steroid and acceptor, whereas its two products are 3-oxo-Delta4-steroid and a reduced acceptor.
Function[]
5-alpha reductases convert testosterone, the male sex hormone, into the more potent dihydrotestosterone:
Note the major difference — the Δ4,5 double-bond on the A (leftmost) ring. (The other differences between the diagrams are unrelated to chemical structure.)
These enzymes also participate in the creation of such neurosteroids as allopregnanolone and THDOC.
Isoenzymes[]
There are two isoenzymes, steroid 5-alpha reductase 1 and 2 (SRD5A1 and SRD5A2).[1][2]
The second isoenzyme is deficient in 5-alpha-reductase deficiency, which leads to a form of intersexualism.
Production and inhibition[]
The enzyme is produced only in specific tissues of the male human body,[3] namely the skin, seminal vesicles, prostate and epididymis.
Inhibition of 5-alpha reductase results in decreased production of DHT, increased levels of testosterone, and, perhaps, increased levels of estradiol. Gynecomastia is a possible side-effect of 5-alpha reductase inhibition.
Pharmacology[]
- Main article: 5-alpha-reductase inhibitor
5-Alpha-reductase inhibitor drugs are used in benign prostatic hyperplasia, prostate cancer, and baldness. Both isoforms are also produced in the brain, where they serve to create the neurosteroid allopregnanolone (5AR type I) and convert T to DHT(5AR type II)(1). Finasteride inhibits the function of only one of the isoenzymes (type 2), whereas dutasteride inhibits both forms.
Research has indicated certain mushrooms have anti-5-alpha reductase activity.[4]
Nomenclature[]
This enzyme belongs to the family of oxidoreductases, to be specific, those acting on the CH-CH group of donor with other acceptors. The systematic name of this enzyme class is 3-oxo-5alpha-steroid:acceptor Delta4-oxidoreductase. Other names in common use include steroid
- 5α-reductase
- 3-oxosteroid Δ4-dehydrogenase
- 3-oxo-5α-steroid Δ4-dehydrogenase
- steroid Δ4-5α-reductase
- Δ4-3-keto steroid 5α-reductase
- Δ4-3-oxo steroid reductase
- Δ4-3-ketosteroid-5α-oxidoreductase
- Δ4-3-oxosteroid-5α-reductase
- 3-keto-Δ4-steroid-5α-reductase
- 5α-reductase
- testosterone 5α-reductase
- 4-ene-3-ketosteroid-5α-oxidoreductase
- Δ4-5α-dehydrogenase
- 3-oxo-5α-steroid:(acceptor) Δ4-oxidoreductase.
References[]
- ↑ Killian J, Pratis K, Clifton RJ, Stanton PG, Robertson DM, O'Donnell L (May 2003). 5alpha-reductase isoenzymes 1 and 2 in the rat testis during postnatal development. Biol. Reprod. 68 (5): 1711–8.
- ↑ Thiele S, Hoppe U, Holterhus PM, Hiort O (June 2005). Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males. Eur. J. Endocrinol. 152 (6): 875–80.
- ↑ Pinna G, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E (October 2008). Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice. Neurochem. Res. 33 (10): 1990–2007.
- ↑ Chen, S., Y.C. Kao (1997). Binding characteristics of aromatase inhibitors and phytoestrogens to human aromatase.. The Journal of Steroid Biochemistry and Molecular Biology 61 (3-6): 107–115.
Further reading[]
- LEVY HR, TALALAY P (1959). Bacterial oxidation of steroids. II. Studies on the enzymatic mechanism of ring A dehydrogenation. J. Biol. Chem. 234 (8): 2014–21.
See also[]
- Cholestenone 5alpha-reductase
- 5α-reductase inhibitors
External[]
Template:CH-CH oxidoreductases Template:Cholesterol and steroid metabolism enzymes
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