Geranyl pyrophosphate synthetase

Croteau, R., Felton, M. and Ronald, R.C. (1980b) Biosynthesis of monoterpenes preliminary characterization of /-encfo-fenchol synthetase from fennel (Foeniculum vulgare) and evidence that no free intermediate is involved in the cyclization of geranyl pyrophosphate to the rearranged product. Archives of Biochemistry and Biophysics 200(2), 534-546. 

Manganese acts as a cofactor of mevalonate kinase and farnesyl pyrophosphate synthetase. Mevalonate kinase and possibly one other manganese-activated enzyme are necessary for the formation of mevalonate from acetate (3). Farnesyl pyrophosphate synthetase acts to add one 5-carbon unit to geranyl pyrophosphate to make farnesyl pyrophosphate (4) (Figure 1). 

Steroids are members of a large class of lipid compounds called terpenes. Using acetate as a starting material, a variety of organisms produce terpenes by essentially the same biosynthetic scheme (Fig. 8). The self-condensation of two molecules of acetyl coenzyme A (CoA) forms acetoacetyl CoA. Condensation of acetoacetyl CoA with a third molecule of acetyl CoA, then followed by an NADPH-mediated reduction of the thioester moiety produces mevalonic acid [150-97-0] (72). Phosphorylation of (72) followed by concomitant decarboxylation and dehydration processes produce isopentenyl pyrophosphate. Isopentenyl pyrophosphate isomerase establishes an equilibrium between isopentenyl pyrophosphate and 3,3-dimethylallyl pyrophosphate (73). The head-to-tail addition of these isoprene units forms geranyl pyrophosphate. The addition of another isopentenyl pyrophosphate unit results in the sesquiterpene (C15) famesyl pyrophosphate (74). Both of these head-to-tail additions are catalyzed by prenyl transferase. Squalene synthetase catalyzes the head-to-head addition of two achiral molecules of famesyl pyrophosphate, through a chiral cyclopropane intermediate, to form the achiral triterpene, squalene (75). 

The stereochemistry is well established, and many questions concerning the overall mechanism of the condensation have now been resolved. Famesyl pyrophosphate synthetase (EC 2.5.1.1) is the key enzyme in the biosynthetic pathways for several classes of terpenes. This enzyme catalyzes l -4 condensation between IPP and DMAPP, or geranyl pyrophosphate, polymerizations that constitute the major building steps of terpenoid biosynthesis (Fig. 21.2) (Poulter and Rilling, 1978 Poulter et al., 1978, 1981). The condensation... 

The enzyme, farnesyl pyrophosphate synthetase (prenyl transferase), is responsible for the condensation of (4.14) with (4.15) to give geranyl pyrophosphate (4.41). The same enzyme mediates addition of a further molecule of (4.14) to (4.41) yielding 2- ran5-farnesyl pyrophosphate (4.19). This is the basic unit for the elaboration of the structurally diverse sesquiterpenes. The results obtained on biosynthesis are as interesting as the sesquiterpene structures. The 2 cis... 

The condensation of dimethyallyl pyrophosphate, an isomerization product of isopentenyl pyrophosphate, with isopentenyl pyrophosphate, has been shown to yield geranyl pyrophosphate (Lynen et al., 1959). The enzyme, isopentenyl pyrophosphate isomerase, has been described (Agranoff et al., 1960). Geranyl pyrophosphate may condense with another molecule of isopentenyl pyrophosphate to yield farnesyl pyrophosphate. The enzyme farnesyl synthetase had been isolated by Lynen et al. (1959). The reductive dimerization of two molecules of... 

Croteau R, Karp F 1979 Biosynthesis of monoterpenes preliminary characterization of bornyl pyrophosphate synthetase from sage Salvia officinalis) and demonstration that geranyl pyrophosphate is the preferred substrate for cyclization. Arch Biochem Biophys 198 512-522... 

Ethylbut-3-enyl pyrophosphate also acts" as a substrate for farnesyl pyrophosphate synthetase with dimethylallyl pyrophosphate or geranyl pyrophosphate as the starter unit to afford homologues of farnesyl pyrophosphate. 

Mash, E. A., G. M. Gurria, and C. D. Poulter, Famesylpyrophos-phate synthetase. Evidence for a rigid geranyl cation-pyrophosphate anion pair, J. Am. Chem. Soc., 103, 3927-3929 (1981). 

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