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Concept
5α-Reductase
Summary
5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of 5α-reductase encoded by the genes SRD5A1, SRD5A2, and SRD5A3.
5α-Reductases catalyze the following generalized chemical reaction:
a 3-oxo-5α-steroid + acceptor a 3-oxo-Δ4-steroid + reduced acceptor
Where a 3-oxo-5α-steroid and acceptor are substrates, and a corresponding 3-oxo-Δ4-steroid and the reduced acceptor are products. An instance of this generalized reaction that 5α-reductase type 2 catalyzes is:
dihydrotestosterone + NADP+ testosterone + NADPH + H+
where dihydrotestosterone is the 3-oxo-5α-steroid, NADP+ is the acceptor and testosterone is the 3-oxo-Δ4-steroid and NADPH the reduced acceptor.
The enzyme is produced in many tissues in both males and females, in the reproductive tract, testes and ovaries, skin, seminal vesicles, prostate, epididymis and many organs, including the Nervous System. There are three isoenzymes of 5α-reductase: steroid 5α-reductase 1, 2, and 3 (SRD5A1, SRD5A2 and SRD5A3).
5α-Reductases act on 3-oxo (3-keto), Δ4,5 C19/C21 steroids as its substrates; "3-keto" refers to the double bond of the third carbon to oxygen. Carbons 4 and 5 also have a double bond, represented by 'Δ4,5'. The reaction involves a stereospecific and permanent break of the Δ4,5 with the help of NADPH as a cofactor. A hydride anion (H−) is also placed on the α face at the fifth carbon, and a proton on the β face at carbon 4.
5α-R1 is expressed in fetal scalp and nongenital skin of the back, anywhere from 5 to 50 times less than in the adult. 5α-R2 is expressed in fetal prostates similar to adults. 5α-R1 is expressed mainly in the epithelium and 5α-R2 the stroma of the fetal prostate. Scientists looked for 5α-R2 expression in fetal liver, adrenal, testis, ovary, brain, scalp, chest, and genital skin, using immunoblotting, and were only able to find it in genital skin.
Official source
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