Figure 1.

Mevalonate pathway for the synthesis of IPP. Two molecules of acetyl-CoA are joined together to form acetoacetyl-CoA (i) in a reaction catalyzed by thiolase with the release of free CoA (CoASH). A third molecule of acetyl-CoA is added by 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase to form HMG-CoA (ii). Compound ii is reduced by HMG-CoA reductase in an NADPH-dependent manner to form (R)-mevalonate (iii), which is the rate-limiting step of the pathway. Compound iii is sequentially phosphorylated by mevalonate kinase and phosphomevalonate kinase to form (R)-mevalonate-5-diphosphate (iv). Finally, iv is decarboxylated by mevalonate-5-diphosphate decarboxylase in an ATP-dependent manner to form IPP (v). Coloring of oxygen atoms is intended to assist in tracking of the chemical origin of the carbon skeleton. P, phosphoryl group; OP_i, inorganic phosphate.