Dimethylallyl pyrophosphate, terpene

So is isopentenyl pyrophosphate the C5 intermediate at last Well, yes and no. There are actually two closely related C5 intermediates, each of which has a specific and appropriate role in terpene biosynthesis. Isopentenyl pyrophosphate is in equilibrium with dimethylallyl pyrophosphate by a simple allylic proton transfer. 

All terpenes are synthesized from dimethylallyl pyrophosphate and isopentenyl pyrophosphate. Both of these five-carbon compounds are synthesized, in turn, in a multistep process from three molecules of acetyl CoA (Section 22.17). 

The overall strategy of terpene biosynthesis from dimethylallyl pyrophosphate and isopentenyl pyrophosphate is summarized in Figure 29.9. 

The isoprene rule is a convenient formalism, but isoprene itself is not the biological precursor of terpenes. Nature instead uses two isoprene equivalents —isopentenyl pyrophosphate and dimethylallyl pyrophosphate. These five-carbon molecules are themselves made from condensation of three acetyl CoA units (Section 21.9). 

Prostaglandins and terpenes are still other classes of lipids. Prostaglandins, which are found in all body tissues, have a wide range of physiological actions. Terpenes arc often isolated from the essential oils of plants. They have an immense diversity of structure and are produced biosynthetically by head-to-tail coupling of two five-carbon isoprene equivalents —isopentenyl pyrophosphate and dimethylallyl pyrophosphate. 

Assume that the three terpenes in Problem 27,22 are derived biosynthetically from isopentenyl pyrophosphate and dimethylallyl pyrophosphate, each of which was iso-topically labeled at the pyrophosphate-boaring carbon atom (Cl). At what positions would the terpenes be isotopically labeled ... 

Most successful attempts to isolate the enzymes involved in terpene biosynthesis have come from these early stages. Crude in vitro systems will frequently convert - [2- C]mevalonic acid (1) into its phosphate (2) and pyrophosphate (3), isopentenyl pyrophosphate (4), and dimethylallyl pyrophosphate (5). However, only traces of radioactivity are recovered from the prenol pyrophosphates (6). As well as phosphorylating mevalonic acid the same enzyme, or a related one, is... 

The formation of terpenes and other isoprenoid lipids involves the condensation of dimethylallyl pyrophosphate with isopentenyl pyrophosphate (29). In this case (Scheme 11), the leaving group is the pyrophosphate (PP) of an allylic pyrophosphate, such as dimethylallyl pyrophosphate, generating an allylic carbonium ion derivative (and inorganic pyrophosphate, which forms as an ion pair with the carbonium ion). The electron-rich agent that adds to the electron-deficient center to form the carbon-carbon bond is the rr-electron density of the isopentenyl pyrophosphate. The stereochemical course of the biosynthesis of complex natural products has been determined and is consistent with such a mechanism (30). 

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). 

Modern research has shown that terpenes do not arise from isoprene it has never been detected as a natural product. Instead, the terpenes arise from an important biochemical precursor compound called mevalonic acid (see above). This compound arises from acetyl coenzyme A, a product of the biological degradation of glucose (glycolysis), and is converted to a compound called isopentenyl pyrophosphate. Isopentenyl pyrophosphate and its isomer 3,3-dimethylallyl pyrophosphate (double bond moved to the second position) are the five-carbon building blocks used by nature to construct all the terpene compounds. 

Biosynthetically, majority of terpenoids are formed via the mevalonic acid, but they may also be formed through methyl-erythritol-4-phosphate (MEP) pathway. The C5 isoprene unit which can be linked together head to tail to form linear chains or cyclized to form rings is considered the building blocks of terpenes. Rather the C5 units exist as isopentenyl pyrophosphate or its isomer dimethylallyl pyrophosphate by enzymatic conversion and phosphorylation from mevalonic acid. The IPP may be considered as the precursor of hemiterpenes. In the biosynthesis of mono- and higher terpenes/terpenoids, the starting molecule is DMAPP, which... 

Although the isoprene rule considers terpenes to be constructed from isoprene units, the actual building blocks are dimethylallyl pyrophosphate and isopentenyl pyrophosphate. 

The reaction between dimethylallyl pyrophosphate and isopentenyl pyrophosphate yields a monoterpene called geranyl pyrophosphate, which is the starting material for all other mono-terpenes (Mechanism 26.5). 

All terpenes are biosynthesized from dimethylallyl pyrophosphate and isopentenyl pyrophosphate. 

The multiples of isoprene units in a terpene serve to classify it Cio, monoterpenes C15, sesquiterpenes C20, diterpenes C30, tri-terpenes to which the steroids are closely related C25, sesterpenes. It is a curious thing to note that the isoprene rule, sound and powerfully useful not least for structure elucidation, has unnatural foundations. Isoprene (4.1) is not a naturally occurring compound. Instead the clay from which the terpenes are so orderly fashioned is isopentenyl pyrophosphate (4.14) and dimethylallyl pyrophosphate (4.15). The latter is seen in many natural compounds, e.g. (4.11) as a prenyl ... 

Both isopentenyl pyrophosphate and dimethylallyl pyrophosphate are needed for the biosynthesis of terpenes. Therefore, some isopentenyl pyrophosphate is converted to dimethylaUyl pyrophosphate in a two-step enzyme-catalyzed reaction. 

Figure 16.2). Dimethylallyl pyrophosphate (DMAPP), the common consohdated metabolite of both pathways, is converted to isoprene by isoprene synthase (IspS). DMAPP and its isomer isopentenyl diphosphate (IPP) are also the building units of terpenes and higher isoprenoids (see Section 16.5) in all living organisms [12]. 

Cell-free extracts and acetone powder preparations from Agave amerkana have been shown to phosphorylate mevalonic acid to give phosphomevalonic acid and thence pyrophosphomevalonic acid at an optimum pH of 7.0. Glutathione and mercaptoethanol enhance the activity of these preparations. Tracer studies with tissue cultures derived from Tanacetum vulgare have revealed the formation of phosphomevalonic acid, pyrophosphomevalonic acid, isopentenyl pyrophosphate, dimethylallyl pyrophosphate, and the incorporation of mevalonic acid into monoterpenes. However, the mono-terpene components of the tissue culture differed from those of the whole plant, sabinene being formed rather than isothujone. 

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)... 

The chemical structure of naturally occurring ais polyisoprenes was determined by 13C NMR spectroscopy using acyclic terpenes and polyprenols as model compounds. The arrangement of the isoprene units along the polymer chain was estimated to be in the order dimethylallyl terminal unit, three trans units, a long block of ais units, and ais isoprenyl terminal unit. This result demonstrates that the biosynthesis of cis-polyisoprenes in higher plants starts from trans,trans,trarcs-geranylgeranyl pyrophosphate. ... 

According to this mechanism, natural rubber chains are expected to have one dimethylallyl terminal unit and one isoprenyl pyrophosphate terminal unit the latter may give rise to a hydroxyl group by hydrolysis. From this point of view, acyclic terpenes in the generalized structure (II) may be appropriate models for the structural characterization of natural polyisoprenes by 13C NMR spectroscopy. 

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