5?-Reduced steroids and human ?(4)-3-ketosteroid 5?-reductase (AKR1D1).

ABSTRACT: 5?-Reduced steroids are non-planar steroids that have a 90° bend in their structure to create an A/B cis-ring junction. This novel property is required for bile-acids to act as emulsifiers, but in addition 5?-reduced steroids have remarkable physiology and may act as potent tocolytic agents, endogenous cardiac glycosides, neurosteroids, and can act as ligands for orphan and membrane bound receptors. In humans there is only a single 5?-reductase gene AKR1D1, which encodes ?(4)-3-ketosteroid-5?-reductase (AKR1D1). This enzyme is a member of the aldo-keto reductase superfamily, but possesses an altered catalytic tetrad, in which Glu120 replaces the conserved His residue. This predominant liver enzyme generates all 5?-dihydrosteroids in the C19-C27 steroid series. Mutations exist in the AKR1D1 gene, which result in loss of protein stability and are causative in bile-acid deficiency.

SUBMITTER: Chen M 

PROVIDER: S-EPMC3971473 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature