CH 461 Lecture Notes - Lecture 7: Hmg-Coa Reductase, Dimethylallyl Pyrophosphate, Isopentenyl Pyrophosphate
Document Summary
Hmg coa reductase is the committed and therefore the regulatory step in cholesterol biosynthesis. If hmg coa is reduced to mevalonate, cholesterol is the only product that can result. The reduction is a two step reaction, which releases the coenzyme a cofactor and converts the thiol bound carboxylic group of hmg coa to a free alcohol. Two nadph molecules supply the reducing equivalents because the thioester must first be reduced to the level of an aldehyde and then to an alcohol. Mevalonate molecules are condensed to a 30 carbon compound, squalene. The alcohol groups of mevalonate are first phosphorylated. Then they multiply phosphorylated mevalonate decarboxylates to make the two compounds isopentenyl pyrophosphate (ipp) and dimethylallyl pyrophosphate (dmapp). mevalonate phosphomevalonate pyrophosphomevalonate. This is a simple sequence of two phosphorylations using atp as the donor: First, the other hydroxyl group of mevalonate accepts a phosphate from atp. The resulting compound rearranges in an enzyme catalyzed reaction, eliminating both.
