Geranylgeranyl pyrophosphate-geranyl

Fig. 20.3. Schematic representation of the main pathways in the lipid metabolism of parasitic flatworms. Boxed substrates are supplied by the host. Pathways present in mammalian systems but absent in parasitic flatworms are shown by open arrows. Abbreviations DAG, diacylglycerol CDP-DAG, cytidine diphosphodiacylglycerol Farnesyl PP, farnesyl pyrophosphate Geranyl PP, geranylpyrophosphate Geranylgeranyl PP, geranylgeranylpyrophosphate FlMG-CoA, hydroxymethylglutaryl-CoA TAG, triacylglycerol PA, phosphatidic acid PC, phosphatidylcholine PE, phosphatidylethanolamine PI, phosphatidylinositol PS, phosphatidylserine.

Suggest a mechanism for the conversion of geranyl pyrophosphate to geranylgeranyl pyrophosphate. 

The five-carbon compound used for the synthesis of ter-penes is isopentenyl pyrophosphate. The reaction of dimethylallyl pyrophosphate (formed from isopentenyl pyrophosphate) with isopentenyl pyrophosphate forms geranyl pyrophosphate, a 10-carbon compound. Geranyl pyrophosphate can react with another molecule of isopentenyl pyrophosphate to form farnesyl pyrophosphate, a 15-carbon compound. Two molecules of farnesyl pyrophosphate form squalene, a 30-carbon compound. Squalene is the precursor of cholesterol. Farnesyl pyrophosphate can react with another molecule of isopentenyl pyrophosphate to form geranylgeranyl pyrophosphate, a 20-carbon compound. Two geranylgeranyl pyrophosphates join to... 

Isoprenoids may possess cis- or frans-configuration with respect to the double bonds. Most are derived from key products (prenyl pyrophosphates) with trans-configuration (geranyl, farnesyl, geranylgeranyl pyrophosphates, etc.). There are, however, also compounds with all-cis configuration such as rubber, or with mixed configuration such as... 

Fig. 2. A section of the isoprenoid pathway illustrating the branch to rubber biosynthesis. Rubber (the product) is synthesized in the cytosol from one molecule of allylic pyrophosphate (the initiator) and many molecules of isopentenyl pyrophosphate (the monomer). Isopentenyl pyrophosphate is produced by the cytosolic mevalonate pathway and by the plastidic methyl-erythritol pathway, as indicated by the shaded boxes. GPP, geranyl pyrophosphate FPP, farnesyl pyrophosphate GGPP, geranylgeranyl pyrophosphate.

GPP. See Geranyl pyrophosphate (GPP) GGPP. See Geranylgeranyl diphosphate (GGPP) Geranylgeranyl pyrophosphate (GGPP)... 

IPP and DMAPP react as shown in Scheme 102.4 to generate geranyl pyrophosphate (GPP), whose further reaction with IPP produce famesyl pyrophosphate (FPP) that reacts with another molecule of IPP to afford geranylgeranyl pyrophosphate (GGPP), representing the linear diterpene C20 precursor. 

Geranyl pyrophosphate can react with another molecule of isopentenyl pyrophosphate to form famesyl pyrophosphate, a 15-carbon compound. Famesyl pyrophosphate can react with another molecule of isopentenyl pyrophosphate to form geranylgeranyl pyrophosphate, a 20-carbon compound. 

FIGURE 4.18. Structure of the allylic oligoisoprene pyrophosphates. DMAPP dimethyl allyl pyrophosphate, GPP geranyl pyrophosphate, FPP famesyl pyrophosphate, GGPP geranylgeranyl pyrophosphate. 

Terpenes are synthesised in organisms by complex mechanisms from isoprene units, isopentenyl phosphate and dimethy-lallyl diphosphate (pyrophosphate). The first product is geranyl diphosphate, which is the universal precursor of monoterpenoids. The reaction of geranyl diphosphate with another molecule of isopentenyl diphosphate yields famesyl diphosphate, which is the precursor of sesquiterpenoids. Further reaction with isopentenyl diphosphate gives geranylgeranyl diphosphate, the precursor of diterpenoids (see Figure 3.10). 

Mevalonate kinase [E.C.2.7.1.36 (5) -> (6)] preparations from several plants are inhibited by geranyl, geranylgeranyl, farnesyl, and phytyl pyrophosphates, the most potent inhibitors being the latter two compounds.This enzyme may, therefore, be a control point of isoprenoid biosynthesis in plants. A cell-free system for conversion of mevalonic acid (5) into mevalonic acid S-pyro-phosphate (7) has been prepared from the sapogenin-producing plant Agave americana. ... 

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