Isoprene pyrophosphate

Mevalonate is converted to isoprene units (isoprene pyrophosphate having five carbons). 

Six isoprene pyrophosphate molecules are converted to squalene (having 30 carbon atoms). 

The activated derivative of isoprene pyrophosphate (IPP), as noted in the Introduction, comprises the five-carbon starting synthon for a host of hydrocarbon-Uke compounds that occur in both animals and plants. The term terpene is customarily used to denote the class of compounds made up of two isoprenes. Triterpene thus comprises compounds built from six isoprenes or 30 carbon atoms. That leads to an enormous number of possible structures since there are few restraints on the manner in which IPP couples. Literally hundreds of 30-carbon triterpene natural products have thus been isolated and characterized. Only one member of that group, lanosterol (4-1), is relevant to this discussion of steroids. 

D-Mevalonic acid is the fundamental intermediate in the biosynthesis of the terpenoids and steroids, together classed as poly-isoprenoids. The biogenetic isoprene unit is isopentenyl pyrophosphate which arises by enzymic decarboxylation-dehydration of mevalonic acid pyrophosphate. D-Mevalonic acid is almost quantitatively incorporated into cholesterol synthesized by rat liver homogenates. 

Isopentenyl pyrophosphate is the biological isoprene unit it contains five carbon atoms connected m the same order as m isoprene... 

The chemical properties of isopentenyl pyrophosphate and dimethylallyl pyrophosphate are complementary m a way that permits them to react with each other to form a carbon-carbon bond that unites two isoprene units Using the tt electrons of its double... 

Section 26 9 Carbon-carbon bond formation between isoprene units can be understood on the basis of nucleophilic attack of the tt electrons of a double bond on a carbocation or an allyhc carbon that bears a pyrophosphate leaving group... 

Biological isoprene unit (Section 26.8) Isopentenyl pyrophosphate, the biological precursor to terpenes and steroids ... 

During the second step, mevalonic acid is implicated in a number of enzymic reactions involving ATP, and is converted to isopentyl pyrophosphate and to its isomer 3,3-dimethylallyl pyrophosphate. Actually, the two compounds constitute the active isoprene , which... 

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)... 

Earlier work by Nancy Bucher showed an ATP requirement for cholesterol biosynthesis. The involvement of phosphorylated intermediates was established by Comforth, Popjak, and their associates in the early 1960s with the discovery of kinases which successively phosphorylated MVA to MVA-P and MVA-P to MVA-PP. MVA-PP was decar-boxylated and dehydrated to give the biological C5 isoprene unit, isopentenyl pyrophosphate. This undergoes successive head-to-tail condensations to give the linear 15C terpenoid, famesyl pyrophosphate. 

In pepper as in many plants, there are two sources of isoprene monomers the mevalonic acid pathway and the plastidal pool from pymvate and glyceraldehyde-3-phosphate [26], Pepper carotenoid biosynthesis uses the plastidal pathway for the isopentyl pyrophosphate monomers and the resident terpenoid synthases and transferases [27], Using the 5-carbon isoprene pool, the prenyl transferases sequentially... 

In Hevea, the MW of the polymer has a bimodal distribution with some polymers in the range of 106 Da and others 105 Da. Both the Hevea polymers and the C55-C120 oligomeric isoprenes appear to have well-controlled molecular weights [270]. In vitro studies reveal the size of the polymer is related to the relative concentrations of the putative primer (farnesyl pyrophosphate or geranylgeranyl pyrophosphate)... 

In similar fashions, the core pathway up to C25 compounds (five isoprene units) is formed by sequential addition of C5 moieties derived from IPP to a starter unit derived from DMAPP. Thus, sesquiterpenes are formed form the precursor 2E, hS-farnesyl pyrophosphate (FPP), and diterpenes from 2E, 6E, IO -geranylgeranyl pyrophosphate (GGPP). The parents of triterpenes and tetraterpenes are formed by reductive coupling of two FPPs or GGPPs, respectively. Rubbers and other polyisoprenoids are produced from repeated additions of C5 units to the starter unit GGPP. 

Stage (J) Condensation of Six Activated Isoprene Units to Form Squalene Isopentenyl pyrophosphate and dimethylallyl pyrophosphate now undergo a head-to-tail condensation, in which one pyrophosphate group is displaced and a 10-carbon chain, geranyl pyrophosphate, is formed (Fig. 21-36). (The head is the end to which pyrophosphate is joined.) Geranyl pyrophosphate undergoes another head-to-tail condensation with isopentenyl pyro-... 

Cholesterol is formed from acetyl-CoA in a complex series of reactions, through the intermediates /3-hydroxy-/3-methylglutaryl-CoA, mevalonate, and two activated isoprenes, dimethylallyl pyrophosphate and isopentenyl pyrophosphate. Condensation of isoprene units produces the noncyclic squalene, which is cyclized to yield the steroid ring system and side chain. 

C]acetyl-CoA is added to a rat liver homogenate that is synthesizing cholesterol, where will the 14C label appear in A3-isopentenyl pyrophosphate, the activated form of an isoprene unit ... 

Addition of Isoprenyl Groups A number of eukaryotic proteins are modified by the addition of groups derived from isoprene (isoprenyl groups). A thioether bond is formed between the isoprenyl group and a Cys residue of the protein (see Fig. 11-14). The isoprenyl groups are derived from pyrophosphorylated intermediates of the cholesterol biosynthetic pathway (see Fig. 21-33), such as famesyl pyrophosphate (Fig. 27-30). Proteins modified in this way include the Ras proteins, products of the ras oncogenes and proto-oncogenes, and G proteins (both discussed in Chapter 12), and lamins, pro-... 

A five-carbon isoprene unit—isopentenyl pyrophosphate (IPP)— is formed by the decarboxylation of 5-pyrophosphomevalonate. The reaction requires ATP. [Note IPP is the precursor of a family of molecules with diverse functions, the isoprenoids. Cholesterol is a sterol isoprenoid. Non-sterol isoprenoids include dolichol (see p. 165) and ubiquinone (see p. 75).]... 

This evidently accounts for the presence of isoprene in the breath.34 Isoprene is also formed by many plants and is released into the atmosphere in large amounts, which contribute to photochemical formation of haze. A Mg2+-dependent enzyme catalyzes the elimination of pyrophosphate.35 Isoprene emissions rise with increasing temperature, and it has been suggested that the isoprene may dissolve in chloroplast membranes and in some way confer increased heat resistance.36 37 Hydrolytic dephosphorylation can lead to dimethylallyl alcohol, which is oxidized in the liver to dimethy-lacrylyl-CoA (Eq. 22-1). 

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