. The chronic steroidogenic response involves the change in the expression of 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 (OMM) to the inner (IMM) mitochondrial membrane 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; in a second step, 17OH-pregnenolone is cleaved at the C₁₇-C₂₀ bond by the lyase activity of the enzyme to produce the C₁₉ androgen dehydroepiandrosterone (DHEA). Cyp17a1 can also convert the pregnenolone derived progesterone to 17OH-progesterone which is then cleaved to C₁₉ androstenedione. This route (not shown) is insignificant in humans but it is used by other species. DHEA can be sulfonated to DHEAS by Sult2a; the reverse reaction is caried out by steroid sulfatase Sts. DHEAS:DHEA ratio links to physiological as well as pathophysiological states. DHEA is converted to androstenediol or to androstenedione by hydroxysteroid dehydrogenase Hsd17b3, and Hsd3b1 or Hsd3b2, respectively. Androstenediol and androstenedione are then converted to testosterone by the action of Hsd3b1 or Hsd3b2, and Hsd17b3, respectively. Testosterone can be oxidized and thus inactivated to its androstenedione precursor by the action of Hsd17b2. In some of the target tissues, testosterone can be converted into its very potent metabolite dihydrotestosterone (DHT) by steroid-5-alpha reductases. DHT has a greater affinity for the androgen receptor and thus is a more powerful initiator of the androgen signaling pathway. To see the ontology report for annotations, GViewer and download, click here

The testosterone biosynthetic pathway is part of the Steroid Hormone Biosynthesis Pathway Suite and the Prostate Cancer Pathway Suite.  Click the name of the suite to view the related pathways.
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