Polyprenol reductase

Polyprenol reductase is an enzyme (EC 1.3.1.94) that catalyzes the reduction of polyprenol to dolichol in a NADP+-dependent reaction, a crucial step in the biosynthesis of dolichol phosphate, which is essential for N-linked glycosylation of proteins in eukaryotes[1][2][4][5][6][7][8][10]. The gene most commonly associated with this function in humans is SRD5A3. Mutations in SRD5A3 cause congenital disorders of glycosylation (CDG), with primary manifestations including neurological and vision problems due to impaired glycosylation[6][7][10]. While polyprenol reductase is related in nomenclature to the steroid 5-alpha-reductase enzyme family, its principal substrate is not a steroid, and its deficiency does not affect steroid hormone biosynthesis. The enzyme is broadly conserved in eukaryotes and archaea, and its inhibition or loss is pathologic, but currently no approved drugs are known to target this enzyme in clinical practice[6][7][10].

Other names

Polyprenal reductasesteroid 5-alpha-reductase 3 (SRD5A3)di-trans,poly-cis-dolichol:NADP+ 2,3-oxidoreductaseDFG10 (yeast)PPRD1 (plants)SRD5A2L1FLJ13352

Enzyme inhibition/blockade would disrupt glycosylation by preventing the reduction of polyprenol to dolichol