The Smooth Endoplasmatic Reticulum

The first step in the steroidogenesis takes place within the mitochondria where CHOL becomes a substrate . The transport of free CHOL from the outer mitochondrial membrane to the inner mitochondrial membrane is facilitated by the steroidogenic acute regulatory protein (StAR). Within the mitochondria CHOL is converted to pregnenolone (PREG) by the side-chain cleavage enzyme known as CYP11A1. The conversion to PREG is the rate-limiting step and the following intermediate steps are taken place in the smooth endoplasmatic reticulum . PREG is either converted to 17α-hydroxypregnenolone (OH PREG) by the 17α-hydroxylase activity of CYP17A1 or converted to progesterone (PROG) by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD). PROG is further converted to 17α-hydroxyprogesterone (OH PROG) by the 17α-hydroxylase activity of CYP17A1, and OH PROG is also formed from OH PREG by 3β-HSD . PREG, OH PREG, PROG and OH PROG represent the progestagens containing 21 carbons. Depending on the reaction order the steroidogenesis splits into two pathways, which both converge in production of androgens; the Δ5–hydroxysteroid- and Δ4–hydroxysteroid pathway. In humans the Δ5–hydroxysteroid pathway using PREG as substrate for OH PREG and DHEA is preferred . 3β-HSD is the enzyme
The hydroxylation of PROG to 11-deoxycorticosterone (11-deoxy COS) and OH PROG to 11-deoxycortisol (11-deoxy COR) is catalyzed by the enzyme 21β-hydroxylase known as CYP21A2 . 11-deoxy COS and 11-deoxy COR move back to the mitochondria and form COS and COR by the action of 11β-hydroxylase known as CYP11β1. Further on in the mitochondria the mineralocorticosteroid ALDO is formed from COS by the enzyme aldosterone synthase, which is also known as CYP11β2. COR moves back to the smooth endoplasmic reticulum where it is converted to the metabolic inactive cortisone (CORNE) by 11β-hydroxysteroid dehydrogenase (11β-HSD