Figure 3

An overview of the cholesterol biosynthesis pathway. The enzymes whose transcripts are upregulated upon P4 exposure are shown by asterisks. The full names of the gene symbols are listed in Additional File 2. The cholesterol is synthesized from acetyl-CoA. HMGCR is the rate limiting enzyme because reduction of 3-hydroxy-3-methylglutaryl CoA to mevalonate is the committed step in cholesterol formation. Mevolanate is converted to isopenthenyl pyrophosphate by three sequential reactions requiring ATP. Then squalene is synthesized from six molecules of isopenthenyl pyrophosphate. Then squalene epoxide is cyclized to lanosterol which is converted into cholesterol. The carbon numbers of some intermediates are shown in parenthesis. P4 upregulates transcripts encoding enzymes located throughout the complex biosynthetic pathway. Whereas PRKAA1/2, PRKAB1/2, PRKAG1/2, the genes for subunits of AMP-dependent protein kinase (AMPK), which inhibits HMGCR, appear not to be regulated by P4 (Additional File 2).