Farnesylpyrophosphat

Farnesylpyrophosphat, more commonly known as farnesyl pyrophosphate (FPP), is an allylic isoprenoid compound bearing a pyrophosphate group. It is an essential intermediate in the mevalonate pathway, participating in the biosynthesis of cholesterol, other isoprenoids, and prenylated proteins.

Biosynthesis and chemistry

FPP is formed in cells by the condensation of isopentenyl pyrophosphate (IPP) with dimethylallyl pyrophosphate (DMAPP) through the action of the enzyme farnesyl pyrophosphate synthase. The resulting C15 farnesyl unit is attached to a pyrophosphate group, rendering FPP a highly reactive, charged donor molecule in subsequent reactions.

Biological roles

FPP serves as a key branch point metabolite. It is a substrate for squalene synthase, which converts FPP into squalene in the cholesterol biosynthetic pathway. It is also the donor molecule for protein prenylation: farnesyltransferases transfer the farnesyl group from FPP to cysteine residues within CaaX motifs on target proteins, promoting their membrane association and function. This process is important for the activity and localization of several signaling proteins, including members of the Ras and Rho families.

Clinical and pharmacological relevance

Because FPP is central to the mevalonate pathway, its production is influenced by statins and other pathway inhibitors. Nitrogen-containing bisphosphonates inhibit farnesyl pyrophosphate synthase, affecting bone resorption therapies. Farnesyltransferase inhibitors have been explored as anticancer agents to disrupt prenylation-dependent signaling, though clinical results have been variable.

See also: mevalonate pathway, farnesyltransferase, protein prenylation, cholesterol biosynthesis, isoprenoids.