Steroid 5 alpha-reductase 3 (SRD5A3)

Steroid 5 alpha-reductase 3 (SRD5A3) is a membrane-bound NADPH-dependent oxidoreductase and member of the 5α-reductase family. It is structurally related to SRD5A1 and SRD5A2, but functionally distinct. SRD5A3 catalyzes the reduction of double bonds in steroid substrates and plays an essential role in converting polyprenol to dolichol, a precursor required for N-linked protein glycosylation. This dual enzymatic activity involves both steroid metabolism (e.g., conversion of testosterone to dihydrotestosterone, DHT) and glycosylation pathways. SRD5A3 is widely distributed in human tissues, including reproductive organs, central nervous system, and liver. Dysregulation of SRD5A3 is implicated in prostate cancer progression and congenital disorders of glycosylation. Dutasteride and finasteride, inhibitors of 5α-reductase activity, can affect SRD5A3 with differing potency. Therapeutic targeting of SRD5A3 may have clinical relevance in hormone-dependent cancers and metabolic disorders, though safety challenges remain due to its broad biological functions.

Other names

3-oxo-5α-steroid 4-dehydrogenase 3Steroid 5α-reductase type 3SRD5A3

Competitive inhibition of steroid reduction activity (dutasteride) Blockade of NADPH-dependent reduction of 3-oxo-Δ4 steroids, including conversion of testosterone to dihydrotestosterone