Mevalonic acid pathway

Terpenoid substances are of broad distribution and diverse function in insects. One set, elaborated by the mandibular glands of Acanthomyops claviger, acts both as a defensive secretion and as an alarm releaser. When fed Cu-labeled acetate or mevalonate, laboratory colonies of these ants produce radioactive citronellal and citral, providing unambiguous evidence for de novo synthesis of these terpenes by the ant. The incorporations of these precursors implicate the mevalonic acid pathway as the likely biosynthetic route. 

It is immediately clear that Acanthomyops need not rely on dietary sources of terpenes but can synthesize citronellal and citral from either acetate or mevalonate. The higher total activity of the citronellal as compared with the citral probably reflects the natural preponderance of citronellal (ca. 90%) in the ant secretion. As the specific activities show, these results are consistent with a common biogenetic origin of both terpenes. In the mevalonic acid pathway as described from other organisms (13), the radioactive carbon of l-C14-mevalonate is lost upon formation of isopentenyl pyrophosphate. 

In Acanthomyops, the strikingly different incorporations following the two mevalonate feedings indicate that mevalonate is not degraded before being built into terpenes but rather is decarboxylated, as in the classical mevalonic acid pathway. 

The isoprenoid side chains of quinones are biosynthesized mainly by the mevalonic acid pathway from acetyl-CoA. Another pathway to biosynthesizing isoprenoids is the so-called non-mevalonate ronte by which isopentenyldiphosphate (IPP) is formed from glyceraldehyde 3-phosphate and pyrnvate. The key molecule is the famesyl-diphosphate (FPP) that accepts other IPP molecules to form polyprenyl diphosphates. 

Plant metabolism can be separated into primary pathways that are found in all cells and deal with manipulating a uniform group of basic compounds, and secondary pathways that occur in specialized cells and produce a wide variety of unique compounds. The primary pathways deal with the metabolism of carbohydrates, lipids, proteins, and nucleic acids and act through the many-step reactions of glycolysis, the tricarboxylic acid cycle, the pentose phosphate shunt, and lipid, protein, and nucleic acid biosynthesis. In contrast, the secondary metabolites (e.g., terpenes, alkaloids, phenylpropanoids, lignin, flavonoids, coumarins, and related compounds) are produced by the shikimic, malonic, and mevalonic acid pathways, and the methylerythritol phosphate pathway (Fig. 3.1). This chapter concentrates on the synthesis and metabolism of phenolic compounds and on how the activities of these pathways and the compounds produced affect product quality. 

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... 

Fig. 11 Natural rubber is produced from a side branch of the ubiquitous isoprenoid pathway, with 3-hydroxy-methyl-glutaryl-CoA (HMG-CoA) as the key intermediate derived from acetyl-CoA by the general mevalonic-acid pathway. Mevalonate diphosphate decarboxylase (MPP-D) produces IPP, which is isomeiized to DMAPP by IPP isomerase (IPI). IPP is then condensed in several steps with DMAPP to produce GPP, FPP and GGPP by the action of a trani-prenyltransferase (TPT). The cA-l,4-polymeiization that yields natural rubber is catalyzed by cA-prenyltransferase (CPT), which uses the non-allylic IPP as substrate. Reprinted from [248], with permission from Elsevier...

Gershenzon, J. Croteau, R. In Recent Advances in Phytochemistry, Biochemistry of the Mevalonic Acid Pathway to Terpenoids Towers, G. H. N. Stafford, H. A., Eds. Plenum Press New Yoik, 1990. pp.99-159. 

The percentage composition of carotenoids in plants depends on growing conditions. The average weight percent ranges are /3-carotene, 25-40% lutein, 40-60% violaxanthin, 10-20% and neoxanthin, 5-13%. Carotenoids are biosynthesized by condensation of acetyl CoA through the mevalonic acid pathway and the Porter-Lincoln pathway. 

Towers, G.H., and H.A. Stafford Biocke/rustry of the Mevalonic Acid Pathway to Terpenoids, Kluwer Academic Publishers. Nonveil. MA, 1990. 

Of the more than 20,000 known species of lichens, only a few have been analyzed and identified as containing biologically active secondary compounds. Most of the unique secondary metabolites that are present in lichens are derived from the polyketide pathway, with a few originating from the shikimic acid and mevalonic acid pathways (Table 1.1). Previous studies have suggested that the para-depsides are precursors to mefa-depsides, depsones, diphenyl ethers, depsidones and dibenzofurans.9,12... 

At present, there is no doubt about the biosynthesis of ABA by the carotenoid pathway via the MEP pathway in plants. If ABA is biosynthesized by the direct pathway, the first cyclized intermediate will be ionylide-neethanol, having a hydroxyl group at C-l derived from farnesol however, ionylideneethanol has not been found in plants, so the direct pathway is not involved in ABA biosynthesis. The mevalonic acid pathway may also be excluded because almost no 13C label was incorporated into the carbons, which would be labeled in the mevalonic acid pathway in a feeding experiment with [l-13C]-D-glucose.640... 

In contrast to plants, it has been shown that fungi biosynthesize ABA via direct pathways from IDP supplied by the mevalonic acid pathway. B. cinerea and Cercospora pini-densiflorae fed with [l-13C]-D-glucose biosynthesized ABA, C-2, C-4, C-6, C-l, C-3, C-5, C-l, C-8, and C-9 of which were labeled with 13C, being coincident with the biosynthesis of IDP by the mevalonic acid pathway (Figure 2 7).640 Fungi produce ABA-related compounds, which are converted to ABA in feeding experiments. l, 4 -tr r-Diol (3) of ABA was found... 

McCaskill, D., and Croteau, R. (1993). Procedures for the isolation and quantification of the intermediates of the mevalonic acid pathway. Anal Biochem 215 142-149. 

Adam, K.P., Thiel, R., Zapp, J. and Becker, H. (1998) Involvement of the mevalonic acid pathway and the glyceraldehyde-pymvate pathway in terpenoid biosynthesis of the liverworts Ricciocarpos natans and Conocephalum conicum. Arch. Biochem. Biophys., 354,181-87. 

Monfar, M., Caelles, C., Balcells, L., Ferrer, A., Hegardt, PC. and Boronat, A. (1990) Molecular cloning and characterization of plant 3-hydroxy-3-methylglutaryl coenzyme A reductase, in Biochemistry of the Mevalonic Acid Pathway to Terpenoids (eds G.H.N. Towers and H.A. Stafford). Plenum, New York, pp. 83-97. 

In higher plants, two independent and differently located pathways are involved in the biosynthesis of these precursors, the classic mevalonic acid pathway and the non-mevalonate pathway. [270]. The... 

Many of the enzymes involved in the mevalonic acid pathway have been described. Fig. (6) however, studies on the genetic modifications of these enzymes are scarce in the literature. Here an attempt has been made to present the most relevant data on the terpenoid pathway, the enzymes involved and the genetic engineering of them. 

Isopentenyl diphosphate isomerase (IPI E.C. 5.3.3.2) catalyzes the isomerization of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMADP), a previous and mandatory step to create the electrophilic allylic diphosphates needed for the condensation reaction generating geranyl diphosphate, Fig. (6). Thus, IPI is an essential enzyme in organisms which synthesize IPP through the mevalonic acid pathway as archaea, eukaryota and some Gram-positive bacteria [275, 305]. 

The basic unit in the biosynthesis of terpenes is the isoprene molecule, isopren-fenylpyrophosphate formed from acetate in the mevalonic acid pathway, which can self-condense in various ways usually head to tail , less frequently, tail to tail or head to head . 

Processes affecting the carbon-isotopic compositions of isoprenoid lipids. The isoprene carbon skeleton is indicated schematically in Figure 27. The corresponding biosynthetic reactant—equivalent in its role to acetyl-CoA—is isopentenyl pyrophosphate. As shown in Figure 29, this compound can be made by two different and fully independent pathways. The mevalonic-acid pathway was until recently thought to be the only route to isoprenoids. The deoxyxylulose-phosphate, or methylerythritol-phosphate, pathway was first discovered in Bacteria by Rohmer and coworkers (Flesch and Rohmer... 

Figure 29. Relationships h een the carbon positions in isopentenyl pyrophosphate and their sources. In the mevalonic-acid pathway, all five caibon positions in isopentenyl pyrophosphate derive from acetate and, in turn from the C-1 + C-6 and C-2 + C5 positions of glucose. In the methyierythritol-phosphate pathway, one carbon derives from the C-3 + C-4 position in glucose. Moreover, the mapping of positions from preciu ors into products of the two pathways differs sharply, as indicated by stmctures of acyclic and steroidal carbon skeletons based on the MVA (a, c) and MEP pathways (b, d).

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