Isoprenoid synthesis

Some proteins can be posttranslationally modified by the addition of prenyl groups. Prenyl groups are long-chain, unsaturated hydrocarbons that are intermediates in isoprenoid synthesis. The farnesyl group has 15 carbons, and the geranylgeranyl has 20 carbons. They are attached to a cysteine residue near the end of the protein as a thiol ether (Protein-S-R). Other proteins can have a long-chain fatty acid (C14=myristoyl, C16=palmitoyl) attached to the amino terminus as an amide. These fatty acid modifications can increase the association of proteins with the membrane. 

Cholesterol is one of the isoprenoids, synthesis of which starts from acetyl CoA (see p. 52). In a long and complex reaction chain, the C27 sterol is built up from C2 components. The biosynthesis of cholesterol can be divided into four sections. In the first (1), mevalonate, a Ce compound, arises from three molecules of acetyl CoA. In the second part (2), mevalonate is converted into isopen-tenyl diphosphate, the active isoprene. In the third part (3), six of these C5 molecules are linked to produce squalene, a C30 compound. Finally, squalene undergoes cycliza-tion, with three C atoms being removed, to yield cholesterol (4). The illustration only shows the most important intermediates in biosynthesis. 

Zhang, D., and Poulter, C.D. (1995). Biosynthesis of non-head-to-tail isoprenoids. Synthesis of I -l and l -3 structures by recombinant yeast squalene synthase. J Am Chem Soc 117 1641-1642. 

Gibbs, R.A., Krishnan, U., Dolence, J.M., and Poulter, CD. (1995). A stereoselective palladium/copper-catalyzed route to isoprenoids synthesis and biological evaluation of 13-methylidenefarnesyl diphosphate. J Org Chem 60 7821-7829. 

Fig. 8.1. Isoprenoid synthesis pathway, related prenyltransferases, and potential therapeutic interventions.

Heintze, A., Goerlach, J., Leuschner, C., Hoppe, R, Hagelstein, R, Schulze-Siebert, D. and Schultz, G. (1990) Rlastidic isoprenoid synthesis during chloroplast development change from metabolic autonomy to division-of-labor stage. Plant Physiol., 93,1121-7. 

THE KETONE BODIES Most of the acetyl-CoA produced during fatty acid oxidation is used by the citric acid cycle or in isoprenoid synthesis (Section 12.3). Under normal conditions, fatty acid metabolism is so carefully regulated that only small amounts of excess acetyl-CoA are produced. In a process called ketogenesis, acetyl-CoA molecules are converted to acetoacetate, /3-hydroxybutyrate, and acetone, a group of molecules called the ketone bodies (Figure 12.7). 

Isoprenoids occur in all eukaryotes. Despite the astonishing diversity of isoprenoid molecules, the mechanisms by which different species synthesize them are similar. In fact, the initial phase of isoprenoid synthesis (the synthesis of isopentenyl pyrophosphate) appears to be identical in all of the species in which this process has been investigated. Figure 12.22 illustrates the relationships among the isoprenoid classes. 

Isoprenoid synthesis is regulated by sterol and non-sterol components of the biosynthetic pathway, oxysterols, and also by physiological factors. The cholesterol content of the... 

IPP) is the other. IPP is synthesized from 3-phospho-5-pyrophosphomevalonate, as shown in Figure 19.19. The first step in isoprenoid synthesis is as follows ... 

Isoprenoid synthesis. This reagent has been used as an isoprene synthon, since cyclobutenes are converted into 1,3-dienes on pyrolysis. For example, the anion (1) reacts with prenyl bromide (5, 64) to give a mixture of (2) and... 

The iterative and convergent protocol using (E)- and/or (Z)-l,4-diiodo-2-methyl-1-butenes is efficient as well as regio- and stereoselective, requiring hardly any isomeric separation even in the synthesis of a decameric isoprenoid. It permits both iterative and convergent modes of construction of oligomeric isoprenoids in any desired ratio of the two modes of operation to best suit a given synthetic task. At any point of synthesis, either the E- or Z-trisubstituted Cs-alkene unit can be incorporated. This synthetic method promises to find many additional applications in the area of isoprenoid synthesis. 

PLASTIDIC ISOPRENOID SYNTHESIS CHANGES PROM AN AUTONOMOUS TO A DIVISION-OP-LABOR STAGE DURING CHLOROPLAST MATURATION... 

Plastidic Isoprenoid Synthesis Changes from an Autonomous to a Division-of-Labor Stage During Chloroplast Maturation 857... 

Schultz, G. and Schulze-Siebert, Chloroplast isoprenoid synthesis in spinach and barley Direct intermediate supply by photosynthetic carbon fixation, in Biological Role of Plant Lipids (P. 

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