Isoprenyl pyrophosphate

Bacitracin (Fig. 4) is a cyclic peptide antibiotic. The lipid II molecule involved in the bacterial cell wall biosynthesis has a C55 isoprenyl pyrophosphate moiety that must be dephosphorylated so that it can reparticipate in another round of lipid II transfer. Bacitracin binds to the isoprenyl pyrophosphate and prevents the dephosphorylation which, in turn, blocks cell wall growth by interfering with the release of the muropeptide subunits to the outside of the bacterial cell membrane. Bacitracin inhibits similar reactions in eukaryotic cells. So, it is systemically toxic but is an effective and widely used topical antibiotic. 

Overhand, M., et al. (1998). Inhibitors of protein farnesyltransferase and protein geranyl-geranyl transferase I Synthesis of homologous diphosphonate analogues of isoprenylated pyrophosphate. Bioorg Chem 26 269-282. 

Conversion of mevalonate to isoprenyl pyrophosphates with loss of CO2 ... 

Isoprenyl pyrophosphates are synthesized by successive phosphorylation of mevalonate with ATP to yield the 5-monophosphate, 5-pyrophosphate, and 5-pyrophospho-3-monophospho derivatives. This last compound is very unstable and loses the 3-phosphate and the carboxyl group to yield isopentenyl pyrophosphate (IPPP), which is iso-merized to 3,3-dimethylallyl pyrophosphate (DMAPP). These reactions, catalyzed by cytosolic enzymes, are shown in Figure 19-13. 

According to this mechanism, natural rubber chains are expected to have one dimethylallyl terminal unit and one isoprenyl pyrophosphate terminal unit the latter may give rise to a hydroxyl group by hydrolysis. From this point of view, acyclic terpenes in the generalized structure (II) may be appropriate models for the structural characterization of natural polyisoprenes by 13C NMR spectroscopy. 

The initial reactions of terpene biosynthesis are catalyzed by short-chain prenyltransferases belonging to the class of trans- or cis- isoprenyl pyrophosphate synthases that catalyze chain elongation of allylic pyrophosphate substrates with IPP to generate linear polymers with defined chain length. Geranyl pyrophosphate... 

In animals, six molecules of isoprenyl pyrophosphate are used to construct the hydrocarbon squalene, which contains a 24-carbon chain and six methyl substituents. Squalene, in... 

The isoprenyl pyrophosphate synthases (IPPS) catalyse the formation of long-chain prenyl pyrophosphates by the addition of an aUylic cation generated from DMAPP, GPP or FPP to one or more molecules of IPP. Terpene synthases are responsible for the conversion of prenyl pyrophosphates into the classic terpene structures a large number of these are cyclic structures so these synthases are also known as terpene cyclases. Protein prenyltransferases catalyse the addition of isoprenoid chains to a protein or peptide. Here we consider mainly the first two of these. 

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