f steroidogenic genes while the acute response involves the quick delivery of cholesterol to the site of the first enzymatic reaction. The rapid flux of cholesterol from the outer to the inner mitochondrial membrane (IMM) is mediated by the StAR protein. The IMM is the site where Cyp11a1, the enzyme catalyzing the first and rate-limiting step in the steroid biosynthetic pathway, is located. Overall there are two major classes of enzymes: the heme-containing cytochrome P450 and the hydroxysteroid dehydrogenase enzymes. The members of P450 superfamily that participate in the pathway are membrane-bound mitochondrial or endoplasmic reticulum (microsome) enzymes that utilize NADPH as an electron donor. Two proteins mediate the mitochondrial electron transfer - the flavin containing Fdxr and the iron-sulfur Fdx1; only one protein mediates the microsomal electron transfer - the P450 (cytochrome) oxidoreductase Por with two flavin cofactors. Dehydrogenases are membrane-bound mitochondrial or microsomal enzymes that utilize NAD or NADPH depending on whether the reaction is oxidation or reduction. The 27-carbon cholesterol is converted to the C₂₁ pregnenolone in a series of three chemical reactions that together constitute the step catalyzed by Cyp11a1. Cyp17a1 catalyzes the conversion of pregnenolone to 17OH-pregnenolone. Isoforms Hsd3b1 and 2 can aditionally generate progesterone from pregnenolone. Cyp17a1 can also convert progesterone to 17OH-progesterone, and 17OH-pregnenolone can be converted to 17OH-progesterone by Hsd3b1 or Hsd3b2. Cyp21a1 acts on 17OH-progesterone to generate 11-deoxycortisol. This is transformed into cortisol by the P450 enzyme Cyp11b1 in the zona fasciculata, or middle zone of the adrenal gland cortex. To see the ontology report for annotations, GViewer and download click here.
[click to see the ontology report for related GO term - GO:0034651, associated KEGG map - map00140 and related entry at Reactome - REACT_11057.2]

The cortisol biosynthetic pathway is part of the Steroid Hormone Biosynthesis Pathway Suite.  Click here to view the entire suite of related pathways.
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