Natural mutagenesis study of the human steroid 5α-reductase 2 isozyme

摘要: The enzyme steroid 5 alpha-reductase utilizes NADPH to reduce the double bonds of a variety substrates with generalized 3-oxo, delta 4,5 structures. One substrate for this membrane-bound is testosterone, whose reduction dihydrotestosterone required embryonic differentiation external male genitalia and prostate. There are two isozymes, designated types 1 2, which have different biochemical pharmacological properties. Inherited deficiencies type 2 result in form pseudohermaphroditism fail develop normally. Here, nine additional mutations gene subjects deficiency described. consequences these mutations, as well 13 previously identified missense were characterized by recreating an expressible cDNA transfecting into mammalian cells. Twelve 22 inactivated enzyme. remaining 10 impaired function affecting either or cofactor binding. Almost all decreased half-life protein, but one enzymes had altered pH optimum. provide insight functional domains protein unusual acidic optimum characteristic isozyme.