Pentose phosphate cycle
From TBI
pentose phosphate pathway (PPP) in yeast.
Contents |
Introduction
The PPP degrades pentose sugars to triose phosphates. It can form a ribose and NADPH producing branch of glycolysis. Riboses enter the nucleotide metabolism as phosphoribose pyrophosphates. NADPH is used in various anabolic pathways, such as reduction of ribonucleotides to deoxyribonucleotides or fatty acid synthesis, but also for redox regulation by glutathione and the thioredoxin systems, ROS (reactive oxygen species) signaling.
The pentose-phosphate pathway (PPP) can be considered as a branch of glycolysis subtracting glucose-6-phosphate and feeding back fructose-6-phosphate and triose phosphates. It provides pentose phosphate sugars for nucleotide metabolism as well as NADPH for biosynthetic reactions. Even though flux measurements show that 10%- % of glucose is shuttled through the PPP (citations??) it has rarely been included in glycolysis models. Flux measurements in yeast species that can live from fatty acids indicate that the upper part of glycolysis runs in the reverse direction (gluconeogenesis), in part to feed the PPP cycle.
A simple model and parameter estimations by transient glucose pulse experiments are proposed by Vaseghi et al. 1999 [1].
The PPP is subject of optimization to construct yeast strains that can use pentose sugars, such xylose and arabinose, as nutrients [2, 3, 4, 5, 6].
models
A transient perturbation experiment (glucose pulse) to estimate parameters for a simple model of the PPP in yeast cells [1].
Interacting pathways
- glycolysis
- G6P -> . -> GAP, F6P
- gluconeogenesis
- nucleotide metabolism
Regulatory genes
Structural genes
Zwf1
glucose-6-phosphate dehydrogenase (G6PD), catalyzes the first step of the pentose phosphate pathway; involved in adapting to oxidatve stress;
- no cluster
Sol3
6-phosphogluconolactonase, catalyzes the second step of the pentose phosphate pathway; weak multicopy suppressor of los1-1 mutation; homologous to Sol2p and Sol1p
- no cluster
Sol4
6-phosphogluconolactonase with similarity to Sol3p
- cluster D
Gnd1
6-phosphogluconate dehydrogenase (decarboxylating), catalyzes an NADPH regenerating reaction in the pentose phosphate pathway; required for growth on D-glucono-delta-lactone and adaptation to oxidative stress
- no cluster
Gnd2
6-phosphogluconate dehydrogenase (decarboxylating), catalyzes an NADPH regenerating reaction in the pentose phosphate pathway; required for growth on D-glucono-delta-lactone
- cluster U
Rpe1
D-ribulose-5-phosphate 3-epimerase, catalyzes a reaction in the non-oxidative part of the pentose-phosphate pathway; mutants are sensitive to oxidative stress
- no cluster
Rki1
ribose-5-phosphate ketol-isomerase; participates in pyridoxine biosynthesis
- cluster B
Tkl1
transketolase, similar to Tkl2p; needed for synthesis of aromatic amino acids
- no cluster
Tkl2
transketolase, similar to Tkl1p; needed for synthesis of aromatic amino acids
- cluster U
Tal1
transaldolase
- no cluster
Metabolites
References
- Vaseghi S, Baumeister A, Rizzi M, and Reuss M. In vivo dynamics of the pentose phosphate pathway in Saccharomyces cerevisiae. Metab Eng 1999 Apr; 1(2) 128-40. doi:10.1006/mben.1998.0110 pmid:10935926.
- Schwender J, Ohlrogge JB, and Shachar-Hill Y. A flux model of glycolysis and the oxidative pentosephosphate pathway in developing Brassica napus embryos. J Biol Chem 2003 Aug 8; 278(32) 29442-53. doi:10.1074/jbc.M303432200 pmid:12759349.
- Sonderegger M, Jeppsson M, Hahn-Hägerdal B, and Sauer U. Molecular basis for anaerobic growth of Saccharomyces cerevisiae on xylose, investigated by global gene expression and metabolic flux analysis. Appl Environ Microbiol 2004 Apr; 70(4) 2307-17. pmid:15066826.
- Jeffries TW and Jin YS. Metabolic engineering for improved fermentation of pentoses by yeasts. Appl Microbiol Biotechnol 2004 Feb; 63(5) 495-509. doi:10.1007/s00253-003-1450-0 pmid:14595523.
- Kleijn RJ, van Winden WA, van Gulik WM, and Heijnen JJ. Revisiting the 13C-label distribution of the non-oxidative branch of the pentose phosphate pathway based upon kinetic and genetic evidence. FEBS J 2005 Oct; 272(19) 4970-82. doi:10.1111/j.1742-4658.2005.04907.x pmid:16176270.
- Frick O and Wittmann C. Characterization of the metabolic shift between oxidative and fermentative growth in Saccharomyces cerevisiae by comparative 13C flux analysis. Microb Cell Fact 2005 Nov 3; 4 30. doi:10.1186/1475-2859-4-30 pmid:16269086.
