Isopentenyl-diphosphate: dimethylallyl

As a general comment, the cations that have been implicated in such biosyntheses are of the type for which analogues have been observed in superacids. However, many of these cations, (e.g., 106 and 109) would have a questionable existence as a free cation in an aqueous solution. This finding raises an interesting question whether they do have more than a fleeting existence within the active site of the enzyme. Does the enzyme provide some form of stabilization, such as that suggested when 106 is formed in the active site of isopentenyl diphosphate dimethylallyl diphosphate isomerase ... 

A central role in the biosynthesis of isoprenoids is filled by the isopentenyl diphosphate-dimethylallyl diphosphate isomerase (IDl) that catalyzes the interconversion of IPP and DMAPP. The necessity for such an enzyme was suggested in the 1950s when only IPP was known as a monomeric isoprenoid precursor, but an allylic diphosphate such as DMAPP was assumed to have the higher intrinsic reactivity for polyisoprenoid synthesis [22, 88, 89]. The first enzymatic isomerization of IPP to DMAPP was observed in 1959 from a cell-free extract of baker s yeast [90, 91]. Two types of IDI with essentially no amino acid sequence or structural similarities are able to catalyze this interconversion by completely different enzyme mechanisms. The well-known IDI-I have been identified in animals, plants, fungi, and bacteria, whereas the IDI-II can be found mainly in archaea but also in some bacteria [92, 93]. 

Identification, 1967, 3369, 3614 Identification tests, 890 IDI. See Isopentenyl diphosphate-dimethylallyl diphosphate-isomerase (IDI) Idioblasts, 1604 IgA nephropathy, 3142 IGF-binding proteins (IGFBPs), 2198 IgGa, 3215... 

Two SN1 reactions occur during the biosynthesis of geraniol, a fragrant alcohol found in roses and used in perfumery. Geraniol biosynthesis begins with dissociation of dimethylallyl diphosphate to give an allylic carbocation, which reacts with isopentenyl diphosphate (Figure IT 15). From the viewpoint of isopentenyl diphosphate, the reaction is an electrophilic alkene addition, but from tile viewpoint of dimethylallyl diphosphate, the process in an Sjjl reaction in which the carbocation intermediate reacts with a double bond as the nucleophile. 

The conversion of isopentenyl diphosphate (IPP) to terpenoids begins with its isomerization to dimethylallyl diphosphate, abbreviated DMAPP and formerly called dimethylallyl pyrophosphate. These two C5 building blocks then combine to give the C10 unit geranyl diphosphate (GPP). The corresponding alcohol, geraniol, is itself a fragrant terpenoid that occurs in rose oil. 

Figure 27.9 Mechanism of the coupling reaction of dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP), to give geranyl diphosphate (GPP).

Isopentenyl diphosphate is isomerized by a shift of the double bond to form dimethylallyl diphosphate, then condensed with another molecule of isopentenyl diphosphate to form the ten-carbon intermediate ger-anyl diphosphate (Figure 26-2). A further condensation with isopentenyl diphosphate forms farnesyl diphosphate. Two molecules of farnesyl diphosphate condense at the diphosphate end to form squalene. Initially, inorganic pyrophosphate is eliminated, forming presqualene diphosphate, which is then reduced by NADPH with elimination of a further inorganic pyrophosphate molecule. 

Rodriguez-Concepcion, M., Campos, N., Lois, L.M. et al. (2000) Genetic evidence of branching in the isoprenoid pathway for the production of isopentenyl diphosphate and dimethylallyl diphosphate in Escherichia coli. FEBS Letters, 473, 328-332. 

Figure 73. The carotenoid biosynthetic pathway. Enzymes are named according to the designation of their genes Ccs, capsanthin-capsorubin synthase CrtL-b, lycopene-b-cyclase CrtL-e, lycopene-e-cyclase CrtR-b, b-ring hydroxylase, CrtR-e, e-ring hydroxylase DMADP, dimethylallyl diphosphate GGDP, geranylgeranyl diphosphate Ggps, geranylgeranyl-diphosphate synthase IDP, isopentenyl diphosphate Ipi, IDP isomerase Pds, phytoene desaturase Psy, phytoene synthase Vde, violaxanthin de-epoxidase Zds, z-carotene desaturase Zep, zeaxanthin epoxidase. (From van den Berg and others 2000.)...

McClard, R.W., Fujita, T.S., Stremler, K.E., and Poulter, C.D., Novel phospho-nylphosphinyl (P-C-P-C-) analogues of biochemically interesting diphosphates. Syntheses and properties of P-C-P-C- analogues of isopentenyl diphosphate and dimethylallyl diphosphate, ]. Am. Chem. Soc., 109,5544,1987. 

The biosynthesis of monoterpenes, the major components of peppermint essential oils, can be divided into four stages (Fig. 9.4). Stage 1 includes the formation of isopentenyl diphosphate (IPP) and dimethylallyl alcohol (DMAPP). In plants, two separate pathways are utilized for the synthesis of these universal C5 intermediates, with the cytosolic mevalonate pathway being responsible for the formation of sterols and certain sesquiterpenes, and the plastidial mevalonate-independent pathway being involved in the biosynthesis of isoprene, monoterpenes, certain sesquiterpenes, diterpenes, tetraterpenes, as well as the side chains of chlorophyll and plastoquinone.16 In peppermint oil gland secretory cells, however, the mevalonate pathway is blocked and the biosynthesis of monoterpenoid essential... 

Ginsenosides are bios)mthesized via the isoprenoid pathway in the cytosol with mevalonic acid as the precursor for isopentenyl diphosphate (IFF) and dimethylallyl diphosphate (DMAPP), which are the two C5 starting units in the bios)mthesis of ginsenosides and other terpenoids... 

Fig. 2. Schematic representation of paclitaxel biosynthesis. Dimethylallyl-diphosphate and isopentenyl-diphosphate are condensed through geranylgeranyl diphosphate synthase activity to render geranylgeranyl-diphosphate (GGPP). GGPP is converted into taxa-4(5), 11 (12)-diene in a reaction catalyzed by the taxane synthase (TS). A series of reactions catalyzed by cytochrome P450 monoxygenases lead to the production of a taxane intermediate that is further converted to baccatin III through enzymes-driven oxidation and oxetane ring formation. The side chain moiety of paclitaxel is derived from L-phenylalanine. Three consecutive arrows mean multiple steps. Ac, acetyl Bz, benzoyl.

Isopentenyl diphosphate isomerase catalyzes the isomerization of isopentenyl diphosphate to dimethylallyl diphosphate (Equation (6)) " ... 

Formation of squalene. Isopentenyl diphosphate undergoes isomerization to form dimethylallyl diphosphate. The two C5 molecules condense to yield geranyl diphosphate, and the addition of another isopentenyl diphosphate produces farnesyl diphosphate. This can then undergo dimerization, in a head-to-head reaction, to yield squalene. Farnesyl diphosphate is also the starting-point for other polyisoprenoids, such as doli-chol (see p. 230) and ubiquinone (see p. 52). 

This enzyme [EC 2.5.1.10], also known as farnesyl-di-phosphate synthase, catalyzes the reaction of geranyl diphosphate with isopentenyl diphosphate to produce trans,trans-farnesyl diphosphate and pyrophosphate (or, diphosphate). Some forms of this enzyme will also utilize dimethylallyl diphosphate as a substrate. However, the enzyme will not accept larger prenyl diphosphates as an efficient substitute for geranyl diphosphate. 

Phytoene synthase [EC 2.5.1.32] (also known as gera-nylgeranyl-diphosphate geranylgeranyltransferase and prephytoene-diphosphate synthase) catalyzes the reaction of two geranylgeranyl diphosphate to produce pyrophosphate (or, diphosphate) and prephytoene diphosphate. Isopentenyl pyrophosphate isomerase [EC 5.3.3.2] catalyzes the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate. See also Geranylgeranyl Diphosphate Geranylgeranyltransferase... 

A second example is isomerization of isopentenyl diphosphate to dimethylallyl diphosphate (Eq. 13-56) 304-307 The stereochemistry has been investigated using the 3H-labeled compound shown in Eq. 13-56. The pro-R proton is lost from C-2 and a proton is added to the re face at C-4. When the reaction was carried out in 2H20 a chiral methyl group was produced as shown.304 A concerted proton addition and abstraction is also possible, the observed trans stereochemistry being expected for such a mechanism. However, the... 

Fig. 2 Biosynthetic route to terpenes. Geranyl diphosphate (5) famesyl diphosphate (6) gera-nylgeranyl diphosphate (7) (-)-limonene (8) (-)-camphene (9) taxadiene (10) casbene (II) capsidiol (12). IPP = isopentenyl diphosphate, DMAPP = dimethylallyl diphosphate...

The absence of dimethylallyl-group in NR indicates that the initiating species for rubber formation in Hevea tree is not FDP, but FDP modified at the dimethylallyl-group, which is abbreviated here as (o [103,109,110]. This was confirmed by 13C-NMR analysis of in vitro polymerised rubber by incubation of the bottom fraction of fresh latex and isopentenyl diphosphate (IDP) [111]. The newly synthesised in vitro rubber formed in the presence of FDP and IDP showed the dimethylallyl group derived from FDP. On the other hand, no dimethylallyl group was detected in the in vivo rubber prepared without the addition of FDP [112]. 

Isoprene itself is not the true biological precursor of terpenoids.. As we ll see in Chapter 27, nature instead uses two "isoprene equivalents"—isopentenyl diphosphate and dimethylallyl diphosphate—which are themselves made by two different routes depending on the organism. Lanosterol, in particular, is biosynthesized from acetic acid by a complex pathway that has been workeo out in great detail. 

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