Two intermediate products of this route are farnesyl-diphosphate (FPP) and geranylgeranyl diphosphate
(GGPP) that participate in the protein prenylation.
The enzymes hydroxymethylglutaryl-CoA reductase, type III geranylgeranyl diphosphate
synthase, phosphomevalonate kinase, hydroxymethylglutaryl-CoA synthase, prenylcysteine oxidase/farnesylcysteine lyase, and protein farnesyltransferase subunit beta are each coded by two copies of the genes.
The pathophysiology of autoinflammation in MKD is poorly understood and is suggested to occur as a result of loss of synthesis of isoprenoid lipids downstream of MVK , in particular geranylgeranyl diphosphate
. This latter is necessary for prenylation (the addition of a hydrophobic compound) of small GTPases, the loss of which causes activation of the inflammasome and release of IL-1[beta] .
The methylerythritol phosphate (MEP) pathway leads to the biosynthesis of geranylgeranyl diphosphate
and the diterpenoid biosynthesis pathway (OKADA, 2007).
A new geranylgeranyl diphosphate
synthase gene from Ginkgo biloba, which intermediates the biosynthesis of the key precursor for ginkgolides.
Likewise, Geranylgeranyl diphosphate
synthase (GGPPS) uses FPP as a substrate and adds another IPP to form Geranylgeranyl diphosphate
(GGPP) with 20 carbons.
Hohl, "Geranylgeranyl diphosphate
synthase: an emerging therapeutic target," Clinical Pharmacology and Therapeutics, vol.
Previous studies supporting the hypothesis that obesity alters isoprenoid signaling include work demonstrating that mice lacking the obesity gene product leptin (ob/ob) exhibit increased expression of the isoprenoid synthesis enzyme geranylgeranyl diphosphate
synthase (GGPS) compared to controls .
By inhibiting FPP synthase, N-BPs prevent the synthesis of FPP and its downstream metabolite geranylgeranyl diphosphate
They are made by the cyclization of geranylgeranyl diphosphate
(GGPP) to form the intermediate elisabethatriene, which is in turn converted to a variety of final products (Figure 6).