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Pyruvate kinase PKM Pyruvate kinase isozymes R/L Solute carrier family 2, facilitated glucose transporter member 2 Mitochondrial pyruvate carrier 1 Monocarboxylate transporter 1 Neutral amino acid transporter B(0) Mitochondrial citrate transport protein Hexokinase-2 Glucose-6- phosphate isomerase 6- phosphofructokinase, liver type Fructose- bisphosphate aldolase B Glyceraldehyde- 3-phosphate dehydrogenase Phosphoglycerate kinase 1 Phosphoglycerate mutase 2 Alpha-enolase Pyruvate carboxylase, mitochondrial Pyruvate dehydrogenase complex Citrate synthase, mitochondrial L-lactate dehydrogenase A-like 6A Aconitate hydratase, mitochondrial Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial Oxoglutarate dehydrogenase complex Succinyl-CoA ligase Succinate dehydrogenase Fumarate hydratase, mitochondrial Malate dehydrogenase, cytoplasmic Glutamate dehydrogenase 1, mitochondrial Glutaminase liver isoform, mitochondrial Transaldolase Transketolase Ribose-5- phosphate isomerase 6- phosphogluconolactonase Glucose-6- phosphate isomerase Glucose-6- phosphate 1-dehydrogenase 6- phosphogluconate dehydrogenase, decarboxylating Cytoplasmic aconitate hydratase Isocitrate dehydrogenase [NADP] cytoplasmic D-Glucose D-Glucose Pyruvic acid Pyruvic acid L-Lactic acid L-Glutamine L-Glutamine L-Glutamine Citric acid Citric acid ATP Glucose 6-phosphate ADP Fructose 6-phosphate ATP Fructose 1,6-bisphosphate ADP D-Glyceraldehyde 3-phosphate NAD Glyceric acid 1,3-biphosphate NADH ADP 3-Phosphoglyceric acid ATP 2-Phospho-D-glyceric acid Phosphoenolpyruvic acid H2O ATP ADP ATP HCO3- ADP Pi Oxalacetic acid CoA NAD Acetyl-CoA CO2 NADH H2O CoA NAD NADH Isocitric acid NAD Oxoglutaric acid CO2 NADH NAD CoA Succinyl-CoA NADH CO2 Pi GDP Succinic acid CoA GTP Q FAD Fumaric acid QH2 FADH2 L-Malic acid H2O NAD NADH L-Glutamic acid H2O NH3 H2O NH3 D-Erythrose 4-phosphate D-Sedoheptulose 7-phosphate D-Ribose 5-phosphate Xylulose 5-phosphate D-Ribulose 5-phosphate 6-Phosphonoglucono-D-lactone H2O 6-Phosphogluconic acid β-D-Glucose 6-phosphate NADP NADPH H+ NADP CO2 NADPH Isocitric acid NADP Oxoglutaric acid NADPH CO2 Magnesium Potassium Magnesium Magnesium Biotin Manganese Thiamine pyrophosphate Lipoamide FAD 4Fe-4S Magnesium Thiamine pyrophosphate Lipoamide FAD Magnesium Thiamine pyrophosphate 4Fe-4S Magnesium L-Lactic acid Lactate shuttle Pentose Phosphate Shunt Citric Acid Cycle Inner Mitochondrial Membrane Outer Mitochondrial Membrane Mitochondrion Cytosol Glycolysis Phosphoenolpyruvic acid Pyruvic acid L-Lactic acid 2-Phospho-D-glyceric acid 3-Phosphoglyceric acid Glyceric acid 1,3-biphosphate D-Glyceraldehyde 3-phosphate Fructose 6-phosphate Fructose 1,6-bisphosphate Pyruvate kinase PKLR L-lactate dehydrogenase Pyruvate kinase PKM The production of ATP through the Citric Acid Cycle is limited to 1%. Lactic acid accumulation leads to a low pH microenvironment The large lactate efflux leads to activation of many factors in adjacent cells involved in angiogenesis. Low conversion of PEP into pyruvate can lead to the accumulation of upstream glycolytic intermediates. Intermediates are used for synthesis of nucleotides, amino acids and fatty acids required in proliferation. Angiogenesis Proliferation Cancer Cell Nucleus
Mitochondria PKM PKLR SLC2A2 MPC1 SLC16A1 SLC1A5 Unknown HK2 GPI PFKL ALDOB GAPDH PGK1 PGAM2 ENO1 PC PDHA1 CS LDHAL6A ACO2 IDH3A IDH3B IDH3G OGDH SUCLG1 SUCLG2 SDHA SDHB SDHC SDHD FH MDH1 GLUD1 GLS2 TALDO1 TKT RPIA PGLS GPI G6PD PGD ACO1 IDH1 D-Glucose D-Glucose Pyruvic acid Pyruvic acid L-Lactic acid L-Glutamine L-Glutamine L-Glutamine Citric acid Citric acid Adenosine triphosphate Glucose 6-phosphate Adenosine diphosphate Fructose 6-phosphate Adenosine triphosphate Fructose 1,6- bisphosphate Adenosine diphosphate D- Glyceraldehyde 3-phosphate NAD Glyceric acid 1,3-biphosphate NADH Adenosine diphosphate 3- Phosphoglyceric acid Adenosine triphosphate 2-Phospho-D- glyceric acid Phosphoenolpyruvic acid Water Adenosine triphosphate Adenosine diphosphate Adenosine triphosphate Hydrogen carbonate Adenosine diphosphate Phosphate Oxalacetic acid Coenzyme A NAD Acetyl-CoA Carbon dioxide NADH Water Coenzyme A NAD NADH Isocitric acid NAD Oxoglutaric acid Carbon dioxide NADH NAD Coenzyme A Succinyl-CoA NADH Carbon dioxide Phosphate Guanosine diphosphate Succinic acid Coenzyme A Guanosine triphosphate Coenzyme Q10 FAD Fumaric acid QH(2) FADH L-Malic acid Water NAD NADH L-Glutamic acid Water Ammonia Water Ammonia D-Erythrose 4-phosphate D-Sedoheptulose 7-phosphate D-Ribose 5-phosphate Xylulose 5-phosphate D-Ribulose 5-phosphate 6- Phosphonoglucono- D-lactone Water 6- Phosphogluconic acid β-D-Glucose 6-phosphate NADP NADPH Hydrogen Ion NADP Carbon dioxide NADPH Isocitric acid NADP Oxoglutaric acid NADPH Carbon dioxide L-Lactic acid
PKM PKLR SLC2A2 MPC1 SLC16A1 SLC1A5 HK2 GPI PFKL ALDOB GAPDH PGK1 PGAM2 ENO1 PC PDHA1 CS LDHAL6A ACO2 IDH3A IDH3B IDH3G OGDH SUCLG1 SUCLG2 SDHA SDHB SDHC SDHD FH MDH1 GLUD1 GLS2 TALDO1 TKT RPIA PGLS GPI G6PD PGD ACO1 IDH1 D-Glc D-Glc Pyr Pyr Lactate Gln Gln Gln CA CA ATP Gluc-6P ADP Fru6P ATP Fru1,6P ADP Glyc3P NAD GlyABp NADH ADP G3P ATP 2PDG Pep H2O ATP ADP ATP HCO3- ADP Pi Oaa CoA NAD Ac-CoA CO2 NADH H2O CoA NAD NADH I-cita NAD AKG CO2 NADH NAD CoA Suc-CoA NADH CO2 Pi GDP Succini CoA GTP Q FAD Fumarat QH2 FADH2 Malate H2O NAD NADH Glu H2O NH3 H2O NH3 D-Ery4P D-SH7P DRib-5P Xyl-5-P RP 6-PGDL H2O 6-PPGA BDGlu6P NADP NADPH H+ NADP CO2 NADPH I-cita NADP AKG NADPH CO2 Mg2+ K+ Mg2+ Mg2+ Biotin Mn2+ ThiamPP Lipoamd FAD 4Fe-4S Mg2+ ThiamPP Lipoamd FAD Mg2+ ThiamPP 4Fe-4S Mg2+ Lactate Lactate shuttle Pentose Phosphate Shunt Citric Acid Cycle Inner Mitochondrial Membrane Outer Mitochondrial Membrane Mitochondrion Cytosol Glycolysis Phosphoenolpyruvic acid Pyruvic acid L-Lactic acid 2-Phospho-D-glyceric acid 3-Phosphoglyceric acid Glyceric acid 1,3-biphosphate D-Glyceraldehyde 3-phosphate Fructose 6-phosphate Fructose 1,6-bisphosphate Pyruvate kinase PKLR L-lactate dehydrogenase Pyruvate kinase PKM The production of ATP through the Citric Acid Cycle is limited to 1%. Lactic acid accumulation leads to a low pH microenvironment The large lactate efflux leads to activation of many factors in adjacent cells involved in angiogenesis. Low conversion of PEP into pyruvate can lead to the accumulation of upstream glycolytic intermediates. Intermediates are used for synthesis of nucleotides, amino acids and fatty acids required in proliferation. Angiogenesis Proliferation Cancer Cell Nucleus
Mitochondria PKM PKLR SLC2A2 MPC1 SLC16A1 SLC1A5 HK2 GPI PFKL ALDOB GAPDH PGK1 PGAM2 ENO1 PC PDHA1 CS LDHAL6A ACO2 IDH3A IDH3B IDH3G OGDH SUCLG1 SUCLG2 SDHA SDHB SDHC SDHD FH MDH1 GLUD1 GLS2 TALDO1 TKT RPIA PGLS GPI G6PD PGD ACO1 IDH1 D-Glc D-Glc Pyr Pyr Lactate Gln Gln Gln CA CA ATP Gluc-6P ADP Fru6P ATP Fru1,6P ADP Glyc3P NAD GlyABp NADH ADP G3P ATP 2PDG Pep H2O ATP ADP ATP HCO3 ADP Pi Oaa CoA NAD Ac-CoA CO2 NADH H2O CoA NAD NADH I-cita NAD AKG CO2 NADH NAD CoA Suc-CoA NADH CO2 Pi GDP Succini CoA GTP Coq FAD Fumarat QH(2) FADH Malate H2O NAD NADH Glu H2O NH3 H2O NH3 D-Ery4P D-SH7P DRib-5P Xyl-5-P RP 6-PGDL H2O 6-PPGA BDGlu6P NADP NADPH H+ NADP CO2 NADPH I-cita NADP AKG NADPH CO2 Lactate