Pregnenolone biosynthesis

The first process in the synthesis of all steroid hormones is the synthesis of pregnenolone from cholesterol. In this process, cholesterol mobilized from cytosolic lipid droplets or from lysosomes is transported to mitochondria and becomes localized to the inner mitochondrial membrane. Cholesterol transport appears to be rate-limiting for steroid hormone synthesis and its regulation, at the step of StAR-mediated traversal of the mitochondrial membrane, plays a central role in determining the amounts and identities of steroid hormones made in the body. In the inner mitochondrial membrane, cholesterol is converted to pregnenolone in a sequence of three reactions, all catalyzed by CYP11A (side chain cleavage enzyme). Finally, pregnenolone re-enters the cytosol.

Summary from Reactome (R-HSA-196108), read 2026-09-23.