farnesylpyrophosphate

Farnesyl pyrophosphate (FPP) is a 15‑carbon isoprenoid diphosphate that serves as a key branch point in the biosynthetic mevalonate pathway. It is synthesized by successive condensations of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) catalysed by farnesyl diphosphate synthase. The reaction proceeds in three stages, with the enzyme adding IPP to DMAPP to form geranyl diphosphate and then adding a second IPP unit to yield FPP.

In eukaryotic cells, FPP is an essential precursor for cholesterol and other sterols. It can be condensed by squalene synthase to produce squalene, the first committed step in sterol biosynthesis. In plants and fungi, FPP serves as the starting substrate for a wide range of terpenoids, including sesquiterpenes, hormone precursors, and secondary metabolites such as resin acids and alkaloids.

Beyond its role as a raw material, FPP functions as a prenyl donor in protein post‑translational modification. Prenyltransferases transfer the farnesyl group from FPP to the C‑terminus of target proteins, a modification that is critical for membrane association and activity of small GTPases such as Rho, Ras, and Rab. This "prenylation" process is therefore essential for signal transduction, vesicle trafficking, and cytoskeletal dynamics.

FPP can be dephosphorylated to farnesol by specific phosphatases, and further metabolised to other isoprenoid alcohols, aldehydes, or acids. It may also be oxidised by cytochrome P450 enzymes to form bioactive derivatives that participate in plant defense and hormone signalling.

Therapeutic strategies targeting FPP synthesis include bisphosphonate drugs, which inhibit farnesyl diphosphate synthase and thereby reduce protein prenylation. Such treatments are used clinically for bone diseases and, experimentally, for anti‑cancer interventions. The modulation of FPP levels continues to be a focus of research into metabolic disorders, infectious disease, and secondary metabolite production.