Geranylgeranylpyrophosphat

Geranylgeranylpyrophosphat, commonly known as geranylgeranyl pyrophosphate (GGPP), is a C20 isoprenoid diphosphate that functions as a donor of the geranylgeranyl group in protein prenylation. It is an intermediate in the mevalonate pathway, synthesized from farnesyl pyrophosphate (FPP) through the action of geranylgeranyl pyrophosphate synthase, with isopentenyl pyrophosphate (IPP) providing the additional five-carbon unit.

GGPP serves as the substrate for protein geranylgeranylation, a post-translational modification that anchors certain proteins to membranes. In eukaryotes, two main enzymes mediate this process: geranylgeranyltransferase I (GGTase I) modifies proteins containing CaaX or related motifs, and Rab geranylgeranyltransferase (GGTase II) catalyzes the addition of geranylgeranyl groups to Rab GTPases with the help of Rab escort protein (REP). A Rab protein may receive two geranylgeranyl groups.

Physiological and pharmacological relevance: The availability of GGPP influences prenylation status and protein function. Disruptions in GGPP synthesis or depletion of isoprenoid intermediates can alter membrane association and trafficking. Statins and bisphosphonates, by lowering mevalonate pathway flux, can reduce GGPP levels and prenylation, with effects studied in cancer, infectious disease, and neurobiology. GGPP is primarily discussed as a biosynthetic intermediate and substrate rather than an enzyme or signaling molecule.

See also: mevalonate pathway, protein prenylation, farnesyl pyrophosphate, isoprenoid biosynthesis.