Glyceraldehyde phosphate/pyruvate pathway, isopentenyl diphosphate

Starting with the simple compounds acetyl-CoA, glyceraldehyde-3-phosphate, and pyruvate, which arise via the central pathways of metabolism, the key intermediate isopentenyl diphosphate is formed by two independent mutes. It is then converted by bacteria, fungi, plants, and animals into thousands of different naturally occurring products. These include high polymers, such as rubber, as well as vitamins, sterols, carotenoids, and over 30,000 different terpenes and related compounds. Many of the latter are found only in specific plants where they may function as defensive compounds or pheromones. 

The terpenes, carotenoids, steroids, and many other compounds arise in a direct way from the prenyl group of isopentenyl diphosphate (Fig. 22-1).16a Biosynthesis of this five-carbon branched unit from mevalonate has been discussed previously (Chapter 17, Fig. 17-19) and is briefly recapitulated in Fig. 22-1. Distinct isoenzymes of 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) in the liver produce HMG-CoA destined for formation of ketone bodies (Eq. 17-5) or mevalonate.7 8 A similar cytosolic enzyme is active in plants which, collectively, make more than 30,000 different isoprenoid compounds.910 However, many of these are formed by an alternative pathway that does not utilize mevalonate but starts with a thiamin diphosphate-dependent condensation of glyceraldehyde 3-phosphate with pyruvate (Figs. 22-1,22-2). 

Figure 22-2 The glyceraldehyde 3-phosphate pyruvate alternative pathway of isoprenoid biosynthesis. The intermediate 1-deoxyxylulose 5-phosphate may enter terpenes, vitamin B6, and thiamin. Isopentenyl diphosphate is shown as the final product, but the intermediate steps are uncertain. See Lange et al 2 ...

Fig. 15.2 Biosynthetic pathway of ubiquinone in prokaryotes. Enzyme names and intermediates are inferred from research studies in E. coli. The chain length of isoprenoids tmd ubiquinone pathway intermediates is kept unspecified (n) to generalize the pathway model to encompass all prokaryotes. (1) eiythtose-4-phosphate (2) phosphoenolpyruvate (3) 3-deoxy-ttfabino-heptulosonate 7-phosphate (4) 3-dehydroquinate (5) 3-dehydroshikimate (6) shikimate (7) shikimate-3-phos-phate (8) 5-enolpyruvyl-shikimate-3-phosphate (9) chorismate (10) para hydroxybenzoate (11) pyruvate (12) glyceraldehyde-3-phosphate (13) l-deoxy-D-xyMose-5-phosphate (14) 2-C-methyl-D-eiythrithol-5-phosphate (15) 4-diphosphocytidyl-2C-methyl-D-erythritol (16) 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate (17) 2-C-methyl-D-erythritol-2,4-cyclo-diphosphate (18) l-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (19) demethylaUyl diphosphate (20) isopentenyl diphosphate (21) farnesyl diphosphate (22) polyprenyl diphosphate (23) 3-polyprenyl-4-hydrobenzoate (24) 2-polyprenylphenol (25) 2-polypienyl-6-hydtoxyphenol ...

Carotenoids are synthesized from the basic C5 terpenoid precursor isopentenyl pyrophosphate (IPP) and dimethylallyl diphosphate (DMAPP). These precursors can be obtained from two distinct pathways the mevalonate pathway (MVA) and the non-MVA pathway also known as 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway [84, 85]. All eukaryotes use the MVA pathway, whereas plant plastids and most bacteria use the MEP pathway [86,87]. Some bacteria also use the MVA pathway [84]. In the MEP pathway, the first step in IPP biosynthesis is the formation of l-deoxy-D-xylulose-5-phosphate (DXP) from pyruvate and glyceraldehyde-3-phosphate catalyzed by DXP synthase (Figure 10.7). DXP is then reduced to MEP by DXP reductase. Additional MEP pathway enzymes are then used in subsequent reactions for converting MEP to IPP, which is isomer-ized to DMAPP by the enzyme IPP isomerase. The MVA pathway begins with the conversion of three molecules of acetyl-CoA to MVA through acetoacetyl-CoA... 

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