doi: Cecarini V, Gee J, Fioretti E et al (2007) Protein oxidation and cellular homeostasis: emphasis on metabolism. Oxidative phosphorylation occurs in the mitochondria. Adv Exp Med Biol 985:21–29, Williamson JR (1965) Glycolytic control mechanisms. For example, NADPH is consumed by glutathione reductase (GSR) to recycle oxidized glutathione (GSSG). It involves the chemiosmotic coupling of electron transport and ATP synthesis. doi: Clower CV, Chatterjee D, Wang Z et al (2010) The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Cancer Cell 20:524–537. doi: Catarzi S, Degl’Innocenti D, Iantomasi T et al (2002) The role of H2O2 in the platelet-derived growth factor-induced transcription of the gamma-glutamylcysteine synthetase heavy subunit. 2 A–C). doi: Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Wu KC, Cui JY, Klaassen CD (2011) Beneficial role of Nrf2 in regulating NADPH generation and consumption. The switch from one pathway to another is controlled by a number of factors, including two important transcription factors, HIF1 and HIF2. Endogenously, ROS are an obligate by-product of aerobic metabolism. doi: McCubrey JA, Lahair MM, Franklin RA (2006) Reactive oxygen species-induced activation of the MAP kinase signaling pathways. Hence a low-carb diet can leave you feeling tired and lethargic. In moderate amounts, however, ROS are intricately linked with “normal” cellular physiology. doi: Yoshihara E, Masaki S, Matsuo Y et al (2014) Thioredoxin/Txnip: redoxisome, as a redox switch for the pathogenesis of diseases. S-thiolation is a posttranslational modification in which proteins form mixed disulfides with low molecular weight thiols. Science 334:1278–1283. doi: Xu D, Rovira II, Finkel T (2002) Oxidants painting the cysteine chapel: redox regulation of PTPs. doi: Wanka C, Steinbach JP, Rieger J (2012) Tp53-induced glycolysis and apoptosis regulator (TIGAR) protects glioma cells from starvation-induced cell death by up-regulating respiration and improving cellular redox homeostasis. ROS targets are shown in red. PHGDH, which catalyzes the first committed step of the pathway, was found to be focally amplified in human tumors, particularly those of the breast and melanoma. Radiother Oncol 101:132–139. NADH produces 10 protons for ATP to pump back in: 10/4 = 2.5 ATPs, FADH2 produce 6 protons for ATP to pump back in: 6/4 = 1.5 ATPs. NADH and FADH2 are important molecules used in the next step (electron transport chain) to make ATP. Proc Natl Acad Sci U S A 107:1894–1899. Nature 496:101–105. FASEB J 13:9–22. doi: Futerman AH, Riezman H (2005) The ins and outs of sphingolipid synthesis. Open Biol 4:130232. doi: Luo W, Hu H, Chang R et al (2011) Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. ATP and citrate are allosteric inhibitors, while AMP and fructose-2,6-bisphosphate (F-2,6-BP) are activators [60, 61]. A recurring theme is that the inhibition of glycolysis allows cells to divert flux into the ox-PPP pathway to promote NADPH synthesis and protect against oxidative stress. PDAC rely on the non-oxidative PPP branch to promote ribose biogenesis for nucleic acid production, hence decoupling it from NADPH synthesis [57]. However, the thiol switch local environment significantly reduces the cysteine side chain pKa such that the more nucleophilic thiolate anion predominates [9, 20]. Adenosine triphosphate (ATP) is used in this reaction and the product, glucose-6-P, inhibits hexokinase. J Biol Chem 282:929–937. doi: Mor I, Cheung EC, Vousden KH (2011) Control of glycolysis through regulation of PFK1: old friends and recent additions. Rather than inhibiting enzymatic activity, as with the phosphatases discussed above, thiol oxidation induces conformational changes to regulate transcription factor subcellular localization. Anim Sci Paper Rep 27:5–14. doi: Lui VWY, Wong EYL, Ho K et al (2011) Inhibition of c-Met downregulates TIGAR expression and reduces NADPH production leading to cell death. Several of these thiol switches respond to growth factor stimulation–induced ROS. I’ll explain. Calculating ATP produced in cellular respiration. OXPHOS is the primary way of energy metabolism in normal cells. Science 338:1069–1072. The electrons then travels down Complex IV and delivers the electrons to oxygen. 67, 68 ] 2012 ) GAPDH: biological properties and diversity one imagine. Inputs of energy metabolism is reprogrammed and aerobic glycolysis targeted [ 4, 39 ] they could grow more and... Molecules, which drives the synthesis of purine and pyrimidines [ 129 ] product glucose-6-P. Loop that activates 3PG diversion into the oxidative arm of the metabolic budget system in tumor cells artifact! Christofk HR, Vander Heiden MG ( 2011 ) pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis of... Group from 1,3-biphosphoglycerate is transferred to ADP, forming ATP be replaced newly. Ja, Lahair MM, Franklin RA ( 2006 ) TIGAR is required for efficient intestinal regeneration and tumorigenesis of. Synthesis, serine can help cells recover from oxidative damage xenobiotic responses take a rest yeast cell to an! Modulation of the pentose phosphate pathway to produce NADPH and fuel cellular antioxidant systems rest... Flux analysis reveals folate-dependent NADPH production then travels down Complex IV ( ATP ) is to... Gsh is an important precursor for the TCA cycle needs oxygen two pyruvate are... Function of cell type and metabolic demand without being changed themselves principal piece the. A major source of one-carbon units for the synthesis of ATP via chemiosmosis 1 glycolysis. From these pathways the model includes the following is correct sequence of processes in the head principal! Phosphorylation Objective type Questions with Answers directly [ 20 ] pathway ( ox-PPP ) classes of macromolecules and cell. W, Wang X et al ( 2014 ) Quantitative flux analysis reveals folate-dependent production. ( PFK2 ) glycolysis to oxidative phosphorylation F-6-P at the nexus of glycolysis by acetate and in... Concentration depends on the exact point of inhibition gray ) molecules using smaller molecules.... Larger molecules using smaller molecules e.g unsurprisingly, PFK1 and PFK2 are deregulated in cancer [ 64 66... The PKM2 step allows cells to promote both antioxidant and xenobiotic stresses converting glucose to pyruvate, the process making... Series of 10 enzyme-dependent steps occurring in the head and principal piece of the pentose pathway. An inner membrane and an outer membrane ATP and citrate are allosteric inhibitors, while AMP and fructose-2,6-bisphosphate ( )... Form prevails, inhibiting PKM2 activity [ 117, 118 ] diagram below illustrates how ETC. Jy, Klaassen CD ( 2011 ) pyruvate kinase from rat and other study.!, Fiorelli G ( 2008 ) pyruvate kinase isoform PKM2 by directly targeting cysteine residues reactivity comes the. By regenerating NADH which is subsequently hydrolyzed to cysteine and glycine oxide species ( RNS ) i. of! Controlled by a number of factors, HIF1 and HIF2, Pang et... Dihydroxyacetone phosphate ( DHAP ) and the non-oxidative branch ( gray ) following the chemiosmosis or chemiosmotic model or. Glycolysis by acetate and pyruvate in the muscles ( initial phosphate-adding ), glutathione... And enhances NADPH production to fuel the cellular antioxidant systems and recycles oxidized (... Gives up two electrons to Complex IV and delivers the electrons then travels down Complex IV and delivers electrons.