DMAPP

The principal steps in the mechanism of polyisoprene formation in plants are known and should help to improve the natural production of hydrocarbons. Mevalonic acid, a key intermediate derived from plant carbohydrate via acetylcoen2yme A, is transformed into isopentenyl pyrophosphate (IPP) via phosphorylation, dehydration, and decarboxylation (see Alkaloids). IPP then rearranges to dimethylaHyl pyrophosphate (DMAPP). DMAPP and... 

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. 

The isomerization of isopentenyl diphosphate to dimethylally diphos phate is catalyzed by JPP isomerase and occurs through a carbocation pathway Protonation of the IPP double bond by a hydrogen-bonded cysteine residue ir the enzyme gives a tertiary carbocation intermediate, which is deprotonated b a glutamate residue as base to yield DMAPP. X-ray structural studies on the enzyme show that it holds the substrate in an unusually deep, well-protectec pocket to shield the highly reactive carbocation from reaction with solvent 01 other external substances. 

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

IPP and its DMAPP structural isomer are produced from glycolytic products by the methyl erythritol phosphate (MEP) pathway (Figure 5.3.1, Pathway 1). These isoprene units are condensed in a stepwise fashion to form the precursor to all carotenoids, geranylgeranyl di-phosphate (GGPP). GGPP is not solely metabolized to make carotenoids, but is a precursor for many other primary and secondary metab-... 

DXP undergoes rearrangement and then is reduced by a reductioisomerase (DXR) to methyl erythritol phosphate (MEP), the first substrate committed to IPP and DMAPP.51.92... 

There are two distinct pathways for biosynthesis of the IPP and DMAPP the mevalonate (MVA) pathway and the DXP pathway (Figure 12.3). The MVA pathway functions primarily in eukaryotes, while the DXP pathway is typically present in prokaryotes and the plastids of plants [90,91]. The first reaction in the DXP pathway is the condensation of pyruvate and D-glyceraldehyde-3-phosphate (G3P) to form DXP, which is catalyzed by DXP synthase encoded by the gene dxs [92]. In the second step, DXP is reduced to 2-C-methyl-D-erythritol-4-phosphate (MEP) by DXP reductoisomerase, which is encoded by the gene dxr (ispC) in E. coli. An array of other enzymes encoded by is pi), ispE, ispF, ispG, and ispH act in subsequent sequential reactions, leading to the conversion of MEP to IPP and DMAPP, which are interconverted by the enzyme encoded by idi [93-97],... 

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... 

Chrysanthemic acid (1) consists of ten carbons, suggesting that it is a monoterpene. The cyclopropane ring of the acid moiety is a feature of pyrethrins. Rivera et al. isolated chrysanthemyl pyrophosphate synthase (CPPase or alternatively referred to as chrysanthemyl diphosphate synthase) underlying the formation of chrysanthemyl pyrophosphate (16) containing a cyclopropane ring from two molecules of dimethylallyl pyrophosphate (15) (DMAPP) and the gene thereof [21]. They found that the reaction involves the cF-2-3 cyclopropanation of DMAPPs in a non-head-to-tail manner. 

The CPPase substrate DMAPP (15) is formed from isopentenyl pyrophosphate (IPP) (14) via the IPP isomerase reaction. It had been assumed that IPP was generated only via mevalonic acid (12) (Fig. 2), but Rohmer discovered another route, 2-C-methyl-D-erythritol 4-phosphate (13) (MEP) pathway (Fig. 2) [22, 23]. A key step in the MEP pathway is the reaction catalyzed by 1-deoxy-D-xylulose 5-phosphate synthase (DXS), which combines hydroxyethyl thiamine pyrophosphate (hydroxyethyl TPP) generated from pyruvic acid (17) and TPP with glyceral-dehyde 3-phosphate (18) to yield 1-deoxy-D-xylulose 5-phosphate (19) containing five carbons. The mevalonate pathway operates in the cytosol of plants and animals, whereas the MEP pathway is present in the plastid of plants or in eubacteria [24-27]. 

More than half of the reported secondary metabolites from macroalgae are isoprenoids. Terpenes, steroids, carotenoids, prenylated quinines, and hydroqui-nones make up the isoprenoid class, which is understood to derive from either the classical mevalonate pathway, or the mevalonate-independent pathway (Stratmann et al. 1992). Melavonic acid (MVA) (Fig. 1.2) is the first committed metabolite of the terpene pathway. Dimethylallyl (dl meth al lal) pyrophosphate (DMAPP) (Fig. 1.3) and its isomer isopentenyl pyrophosphate (IPP, Fig. 1.3) are intermediates of the MVA pathway and exist in nearly all life forms (Humphrey and Beale 2006). Geranyl (ja ran al) (C10) and famesyl (C15) units are generated by head-to-tail (Fig. 1.3) condensation of two (for C10) or three (for C15) 5-carbon DMA-like isoprene units, identifiable in final products by the characteristic fish-tail repeating units, as traced over the structure of a sesquiterpene in Fig. 1.3 (Humphrey and Beale 2006). Additional IPP condensation with famesyl pyrophosphate (FPP)... 

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... 

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