Isopentenyl diphosphate structure

In the Chapter 6 Focus On, "Terpenes Naturally Occurring Alkenes," we looked briefly at terpenoids, a vast and diverse group of lipids found in all living organisms. Despite their apparent structural differences, all terpenoids are related. All contain a multiple of five carbons and are derived biosynthetically from the five-carbon precursor isopentenyl diphosphate (Figure 27.6). Note that formally, a... 

The terpenoid precursor isopentenyl diphosphate, formerly called isopentenyl pyrophosphate and abbreviated IPP, is biosynthesized by two different pathways depending on the organism and the structure of the final product. In animals and higher plants, sesquiterpenoids and triterpenoids arise primarily from the mevalonate pathway, whereas monoterpenoids, diterpenoids, and tetraterpenoids are biosynthesized by the 1-deoxyxylulose 5-phosphate (DXP) pathway. In bacteria,... 

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. 

Eicosanoids and terpenoids are still other classes of lipids. Eicosanoids, of which prostaglandins are the most abundant kind, are derived biosynthetically from arachidonic acid, are found in all body tissues, and have a wide range of physiological activity. Terpenoids are often isolated from the essential oils of plants, have an immense diversity of structure, and are produced biosynthetically from the five-carbon precursor isopentenyl diphosphate (IPP). lsopentenyl diphosphate is itself biosynthesized from 3 equivalents of acetate in the mevalonate pathway. 

Diterpenoids are derived biosynthetically from geranylgeranyl diphosphate (GGPP), which is itself biosynthesized by reaction of farnesvl diphosphate with isopentenyl diphosphate. Show the structure of GGPP, and propose a mechanism for its biosynthesis horn FPP and IPP. 

Subsequent cyclizations, dehydrogenations, oxidations, etc., lead to the individual naturally occurring carotenoids, but little is known about the biochemistry of the many interesting final structural modifications that give rise to the hundreds of diverse natural carotenoids. The carotenoids are isoprenoid compounds and are biosynthesised by a branch of the great isoprenoid pathway from the basic C5-terpenoid precursor, isopentenyl diphosphate (IPP). The entire biosynthesis takes place in the chloroplasts (in green tissues) or chromoplasts (in yellow to red tissues). 

Most terpenoids are derived from mevalonic acid (MVA) through the universal precursor isopentenyl diphosphate (IPP) and its allylic isomer dimethylallyl diphosphate (DMAPP). Thus, the vast majority of terpenoids contain the basic structural residue 2-methylbutane, often less precisely referred to as isoprene units. These C5 hemiterpene units combine with... 

The isoprenoids are derived from mevalonic acid (MVA), which is formed from three molecules of acetyl-CoA (Fig. 3). Two molecules of acetyl-CoA are condensed, yielding acetoacetyl-CoA. Subsequently, this product is coupled with another molecule of acetyl-CoA to yield 35-hydroxy-3-methylglutaryl-CoA (HMG-CoA). By reduction of HMG-CoA MVA is obtained. MVA is further converted in some steps to yield the Cs-unit isopentenyl diphosphate (IPP), which is then isomerized to dimethy-lallyl diphosphate (DMAPP), the starter molecule of the isoprenoid pathway. Coupling of DMAPP with one or more IPP molecules yields the basic structures which form the backbone of terpenoid biosynthesis. A number of reviews on the early steps in the terpenoid biosynthesis have been published (70-77). 

Poly(c -l,4-isoprene) belongs to the family of polyisoprenoids, which are the most structurally diverse and abundant natural products known, with more than 23,000 primary and secondary metabolites. This huge family comprises, for example, sterols which display not only structural functions (control of biological membrane fluidity) but also hormonal functions (steroid hormones). Key phyto-hormones, such as abscisic acid, gibberellins and cytokinins, are isoprenoids too. Moreover, isoprenoids are used in protein prenylation, which is a key step in the activation and the localization of metabolic enzymes in many organisms. The first common step of all isoprenoid biosynthesis pathways is the formation of isopentenyl diphosphate (IPP). ... 

Isopentenyl diphosphate and dimethylallyl diphosphate are structurally similar—both contain a double bond and a diphosphate ester unit—but the chemical reactivity expressed by each is different. The principal site of reaction in dimethylallyl diphosphate is the carbon that bears the diphosphate group. Diphosphate is a reasonably good leaving group in nucleophilic substitution reactions, especially when, as in dimethylallyl diphosphate, it is located at an allylic carbon. Isopentenyl diphosphate, on the other hand, does not have its leaving group attached to an allylic carbon and is far less reactive than dimethylallyl diphosphate toward nucleophilic reagents. The principal site of reaction in isopentenyl diphosphate is the carbon-carbon double bond, which, like the double bonds of simple alkenes, is reactive toward electrophiles. 

Beyond this direct effect played by isoprene, the five carbons of dimethylallyl diphosphate and isopentenyl diphosphate serve as realized precursors to the idealized concept of thousands of naturally occurring compounds whose structures are multiples of C5 and with the particular branching seen there. Although not originally recognized as such, they may be considered as the parent of 2-methyl-l,3-butadiene or isoprene, and it is from here that the concept of an isoprene rule begins. ... 

Problem 11.4. Examine the structure of (5)-(+)-solanone in Figure 11.21. It is clear that it cannot follow the pattern dictated by the isoprene rule, which has sets of live carbons added in a linear fashion from isopentenyl diphosphate to geranyl diphosphate to farnesyl diphosphate as shown earlier. Of course, (5)-(+)-solanone also has only 13 carbon atoms. How might it have, nevertheless, been formed ... 

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]. 

As artemisinin has a terpenic structure, its biosynthesis starts in the formation of isopentenyl diphosphate GPP)> as in all the natural terpenoids. In plants, IPP is synthesized either via the mevalonate pathway in the cytosol or via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in the plastid. The IPP derived from the mevalonate pathway is generally used in the biosynthesis of sesquiterpenes (such as artemisinin), phytosterols, and triterpenes, and the IPP derived from the non-mevalonate pathway is employed in the biosynthesis of monoterpenes, diterpenes, and tetraterpenes (Fig. 89.15). 

As Taxol has a diterpenic structure, its biosynthesis starts in the formation of isopentenyl diphosphate (IPP) via the 2-C-methyl-D-erythritol 4-phosphate (MEP)... 

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