Isopentenyl pyrophosphate compounds derived from

Isoprenoid Any of a number of hydrophobic compounds derived from the polymerization of isopentenyl pyrophosphate and its isomer, dimethy-lallyl pyrophosphate. The isoprene unit is a five-carbon branched hydrocarbon (2-methyl-l,3-butadiene). 

The synthesis of mevalonate is required not only for the synthesis of cholesterol but also for the synthesis of a number of other important compounds derived from isopentenyl pyrophosphate, including ubiquinone (CoQ), an important component of the electron transport chain. Therefore, the complete blockage of mevalonate synthesis, even if adequate cholesterol is available in the diet, would be ill-advised. 

Mevalonic acid (MVA) is transformed into isopentenyl pyrophosphate (IPP) by decarboxylation, and is further transformed into dimethylallyl pyrophosphorate (DMAPP). IPP and DMAPP are the fundamental building blocks that are incorporated into terpenoids. Terpenoids are therefore regarded as compounds derived from the combination of multiple C5 units. These biosynthetic pathways are demonstrated by specific incorporation studies with T( H)- and C-labeled compounds [2-5],... 

The steroid hormones (glucocorticoids, mineralocorticoids, and sex hormones) are produced from cholesterol by alteration of the side chain and introduction of oxygen atoms into the steroid ring system. In addition to cholesterol, a wide variety of isoprenoid compounds are derived from mevalonate through condensations of isopentenyl pyrophosphate and dimethylallyl pyrophosphate. 

The biosynthesis of monoterpenoids and camphor has been described by several authors (108-llU). Ruzicka (115,116) proposed a unified biogenetic scheme for terpenes. The biosynthetic building blocks for these terpenes are iso-prene units. The biosynthetically active isoprene units are isopentenyl pyrophosphate [l] and dimethyl allyl pyrophosphate [2] the compounds that are derived from acetate via mevalonic acid (Scheme V). Geranyl pyrophosphate [3] is the C-10 precursor for the terpenes (117). Banthorpe and Baxendale (ll8) confirmed the biosynthetic pathway of (iamphor via acetate mevalonate by conducting degradation study of camphor, biosynthesized from l c labelled mevalonic acid. The biosynthesis of camphor is summarised in Scheme VI. 

All 27 carbon atoms of cholesterol are derived from acetyl Co A. First acetyl CoA and acetoacetyl CoA combine to form HMG CoA which, in turn, is reduced to mevalonate by HMG CoA reductase. Mevalonate is converted into the five-carbon isoprene compounds 3-isopentenyl pyrophosphate and its isomer dimethylallyl pyrophosphate. These two compounds condense to form the CIO geranyl pyrophosphate, which is elongated to the C15 farnesyl pyrophosphate by the addition of another molecule of isopentenyl pyrophosphate. Two molecules of farnesyl pyrophosphate condense to form the C30 squalene, which is then converted via squalene epoxide and lanosterol to cholesterol. 

The mevalonate pathway in the cytosol is responsible for biosynthesis of sterols, sesquiterpenes, and triterpenoids. After conversion of mevalonic acid to isopentenyl pyrophosphate, three C5 units can be joined head to tail to produce a C15 compound, famesyl pyrophosphate. Two famesyl pyrophosphates are then united head to head to form squalene, the progenitor of the C30 isoprenoids from which sterols are derived. The plant squalene synthetase, like its mammalian homologue, is found in the ER and the reaction proceeds via a presqualene pyrophosphate intermediate (Chapter 14). In the last step prior to cyclization, squalene is converted to squalene 2,3-epoxide. 

Cell-free extracts have been obtained from Claviceps paspali cultures which catalyse the formation of (115) and (120) from tryptophan and isopentenyl pyrophosphate. Both compounds were incorporated into lysergic acid amide. Another unidentified compound has been isolated as a product of the incubation, derived from (120) and convertible into lysergic acid amide " cf. ref. 9. 

This complexity of EOs phytochemistry led to a certain inconsistency of the chemical composition of an essential oil. In fact, several factors influence the balance of the compounds within EOs. Terpenoids and isoprenoid are synthesized through secondary metabolism of the plant. Monoterpenes are biosynthesized in plastid via two 5-carbon precursors, that is, isopentenyl pyrophosphate and dimethylallyl pyrophosphate, which condense to give the monoterpenes (10-carbon). The sesquiterpenes (15-carbon) are formed via the mevalonate pathway in the cytosol. Phenylpropanoids are derived mainly from the shikimate pathway [5]. 

As a glance at their structural formulae shows terpenoids are obviously constructed from 5 C building blocks. Recognition of this fact was summarized by Ruzicka in the Isoprene Rule. Indeed, it was first assumed that the known chemical compound isoprene is the naturally occurring 5 C building block. It is now known that it is the so-called active isoprene, isopentenyl pyrophosphate (IPP), and not isoprene itself, that plays a role in the biosynthesis of the terpenoids. The alternative name isoprenoids for the group of the terpenoids is derived from isoprene or active isoprene. 

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