Fig. 3

The mevalonate pathway and its transcriptional regulation. The mevalonate pathway begins with the end-product of glycolysis, acetyl-CoA, which is metabolized through several enzymatic steps to mevalonate, IPP, GPP, FPP, GGPP and cholesterol. Both FPP and GGPP can be post-translationally added to proteins, especially small monomeric GTPases (such as Ras, Rho, or Rac). Cholesterol is produced by cells via the mevalonate pathway or LDLR-mediated LDL endocytosis from the serum. When intracellular cholesterol levels are low, SCAP mediates the translocation of SREBP2 to the Golgi apparatus, where it is cleaved by proteases. The active N-terminal fragment is released and translocated to the nucleus, where it binds to the SRE regions of the HMGCR and LDLR promoters to induce gene expression. The inhibitory feedback mechanism mediated by cholesterol is indicated in blue. The mevalonate pathway can be blocked by statins