Geranylgeranyl pyrophosphate

Whereas dimerization of two famesyl pyrophosphates (35) generates squalene (114) on the path to steroids (89), the addition of one more C unit, as isopentenyl pyrophosphate (31) or its isomer, 3,3-dimethyl ally pyrophosphate (32), to the C compound famesyl pyrophosphate produces the C2Q diterpene precursor geranylgeranyl pyrophosphate [6699-20-3] (122). 

Geranylgeranyl pyrophosphate [6699-20-3 (NH4 salt)] M 450.5, pKEst(i)-<2, pKesk2) <2, pKEst(3) 3.95, pKes,(4) 6.26. Purified by counter-current distribution between two phases of a... 

AiTKEN s M, ATTUCCi s, IBRAHIM R K. and GULIK p J (1995) A cDNA encoding geranylgeranyl pyrophosphate synthase from white lupin . Plant Physiol, 108, 837-8. 

KUNTZ M, ROMER s, suiRE c, HUGUENEY p, WEIL j H, scHANTZ R and CAMARA B (1992) Identification of a cDNA for the plastid-located geranylgeranyl pyrophosphate synthase from Capsicum annuum correlative increase in enzyme activity and transcript level during fruit ripening , Plant J, 2, 25-34. 

Ament K, Van Schie CC, Bouwmeester HJ, Haring MA, Schumink RC (2006) Induction of a leaf specific geranylgeranyl pyrophosphate synthase and emission of (it -4,8,12-trimethyltrideca-l,3,7,ll-tetraene in tomato are dependent onboth jasmonic acid and salicylic acid signahng pathways. Planta 224 1197-1208... 

In Hevea, the MW of the polymer has a bimodal distribution with some polymers in the range of 106 Da and others 105 Da. Both the Hevea polymers and the C55-C120 oligomeric isoprenes appear to have well-controlled molecular weights [270]. In vitro studies reveal the size of the polymer is related to the relative concentrations of the putative primer (farnesyl pyrophosphate or geranylgeranyl pyrophosphate)... 

In similar fashions, the core pathway up to C25 compounds (five isoprene units) is formed by sequential addition of C5 moieties derived from IPP to a starter unit derived from DMAPP. Thus, sesquiterpenes are formed form the precursor 2E, hS-farnesyl pyrophosphate (FPP), and diterpenes from 2E, 6E, IO -geranylgeranyl pyrophosphate (GGPP). The parents of triterpenes and tetraterpenes are formed by reductive coupling of two FPPs or GGPPs, respectively. Rubbers and other polyisoprenoids are produced from repeated additions of C5 units to the starter unit GGPP. 

Although sterols like cholesterol are not synthesized de novo by parasitic flatworms, they do possess an active mevalonate pathway (Fig. 20.3) (reviewed in Coppens and Courtoy, 1996). This pathway has been studied in 5. mansoni, and all available evidence indicates that it is similar to the lipid metabolism seen in F. hepatica. The mevalonate pathway was shown to be used by 5. mansoni for the synthesis of dolichols for protein glycosylation, of quinones as electron transporters in the respiratory chain and of farnesyl and geranylgeranyl pyrophosphates as substrates for the isopreny-lation of proteins (Chen and Bennett, 1993 Foster et a/., 1993). A key enzyme in the mevalonate pathway is 3-hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) and it was shown that the schistosomal enzyme differs from the mammalian type, both structurally and in its regulatory properties (Rajkovic et ai, 1989 Chen et at., 1991). Farnesyl pyrophosphate plays a key role in the mevalonate pathway as it is the last common substrate for the synthesis of all end products (Fig. 20.3). As mentioned already, the branch leading from farnesyl pyrophosphate via squalene to cholesterol is not operative in parasitic flatworms, whereas the other branches are active, at least in S. mansoni and probably also in F. hepatica and FI. diminuta. 

Isopentenyl pyrophosphate acts as an alkylating agent toward famesyl pyrophosphate. Alkylation is followed by loss of a proton from the carbocation intermediate, giving geranylgeranyl pyrophosphate. Hydrolysis of the pyrophosphate yields geranylgeraniol. 

Farnesyl pyrophosphate and the C20 compound geranylgeranyl pyrophosphate (which is formed by the condensation of another isopentenyl pyrophosphate with farnesyl pyrophosphate) are covalently linked to cysteine residues in a number of proteins, promoting their association with membranes (see Topic E2). Dolichol, which contains some 20 isoprene units is used to carry the biosynthetic precursor of the N-linked oligosaccharides that are subsequently attached to proteins (see Topic H5). 

A diterpene hydrocarbon, assigned the trivial epithet nasutene, has been reported to be the trail pheromone of Nasutitermes exitiosus (27). This compound, which contains an unusual 14-membered ring structure, has been assigned the structure of neocembrene-A (I). Neocembrene can be derived from Cp CiA cyclization of geranylgeranyl pyrophosphate. 

The larger terpenes are formed in the same manner as the monoterpenes and sesquiterpenes. The precursor for the diterpenes is the C2o compound geranylgeranyl pyrophosphate, which is formed from farnesyl pyrophosphate in a manner similar to that shown in Figure 28.2 ... 

Suggest a mechanism for the conversion of geranylgeranyl pyrophosphate to Iabdadi-enyl pyrophosphate. 

Show a mechanism for the formation of sclareol from geranylgeranyl pyrophosphate. 

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