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cAMP-dependent protein kinase catalytic subunit alpha cAMP-dependent protein kinase catalytic subunit beta cAMP-dependent protein kinase type I-alpha regulatory subunit cAMP-dependent protein kinase catalytic subunit gamma cAMP-dependent protein kinase type I-beta regulatory subunit cAMP-dependent protein kinase type II-beta regulatory subunit cAMP-dependent protein kinase type II-alpha regulatory subunit 6- phosphofructo- 2- kinase/fructose- 2,6- bisphosphatase 1 cAMP-dependent protein kinase catalytic subunit alpha cAMP-dependent protein kinase catalytic subunit beta cAMP-dependent protein kinase type I-alpha regulatory subunit cAMP-dependent protein kinase catalytic subunit gamma cAMP-dependent protein kinase type I-beta regulatory subunit cAMP-dependent protein kinase type II-beta regulatory subunit cAMP-dependent protein kinase type II-alpha regulatory subunit 6- phosphofructo- 2- kinase/fructose- 2,6- bisphosphatase 1 6- phosphofructokinase, liver type Fructose-1,6- bisphosphatase 1 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 NADH-ubiquinone oxidoreductase chain 1 NADH-ubiquinone oxidoreductase chain 2 NADH dehydrogenase [ubiquinone] 1 subunit C2, isoform 2 NADH-ubiquinone oxidoreductase chain 3 NADH-ubiquinone oxidoreductase chain 4 NADH-ubiquinone oxidoreductase chain 4L NADH-ubiquinone oxidoreductase chain 5 NADH-ubiquinone oxidoreductase chain 6 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 Cytochrome c oxidase subunit NDUFA4 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial Acyl carrier protein, mitochondrial NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial NADH dehydrogenase [ubiquinone] 1 subunit C2 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial 5'-AMP- activated protein kinase catalytic subunit alpha-1 5'-AMP- activated protein kinase subunit gamma-1 5'-AMP- activated protein kinase subunit beta-1 Acetyl-CoA carboxylase 1 Adenylate cyclase type 10 Glucagon receptor Glucagon cAMP-dependent protein kinase catalytic subunit alpha cAMP-dependent protein kinase catalytic subunit beta cAMP-dependent protein kinase type I-alpha regulatory subunit cAMP-dependent protein kinase catalytic subunit gamma cAMP-dependent protein kinase type I-beta regulatory subunit cAMP-dependent protein kinase type II-beta regulatory subunit cAMP-dependent protein kinase type II-alpha regulatory subunit Serine/threonine- protein kinase SIK2 cAMP-specific 3',5'-cyclic phosphodiesterase 4B cAMP-dependent protein kinase catalytic subunit alpha cAMP-dependent protein kinase catalytic subunit beta cAMP-dependent protein kinase type I-alpha regulatory subunit cAMP-dependent protein kinase catalytic subunit gamma cAMP-dependent protein kinase type I-beta regulatory subunit cAMP-dependent protein kinase type II-beta regulatory subunit cAMP-dependent protein kinase type II-alpha regulatory subunit Pyruvate kinase isozymes R/L Solute carrier family 2, facilitated glucose transporter member 2 Calcium-binding mitochondrial carrier protein Aralar1 Mitochondrial 2- oxoglutarate/malate carrier protein ADP/ATP translocase 4 Solute carrier family 22 member 1 Glucose-6- phosphate isomerase Glucose-6- phosphatase Fructose- bisphosphate aldolase B Triosephosphate isomerase Glycerol-3- phosphate dehydrogenase [NAD(+)], cytoplasmic Alpha-enolase Phosphoenolpyruvate carboxykinase, cytosolic [GTP] Malate dehydrogenase, cytoplasmic Malate dehydrogenase, cytoplasmic Aspartate aminotransferase, mitochondrial Adenylate kinase isoenzyme 1 Fatty acid synthase Phosphoenolpyruvate carboxykinase, cytosolic [GTP] Glucose-6- phosphatase Phosphoglycerate kinase 1 Phosphoglycerate mutase 1 D-Fructose 2,6- bisphosphate D-Fructose 2,6- bisphosphate AMP 1,1-Dimethylbiguanide 1,1-Dimethylbiguanide Oxaloacetate NADH FADH2 ATP D-Glucose D-Glucose L-Aspartic acid L-Aspartic acid L-Glutamic acid L-Glutamic acid Malate Malate Oxoglutaric acid Oxoglutaric acid Malate Oxaloacetate Oxaloacetate H+ H+ ATP ADP ADP 1,1- Dimethylbiguanide Glucose 6-phosphate Fructose 6-phosphate Pi H2O Fructose 1,6- bisphosphate H2O Pi ATP ADP D- Glyceraldehyde 3-phosphate Dihydroxyacetone phosphate Pi NAD Glyceric acid 1,3-biphosphate NADH H+ 2- Phosphoglyceric acid Phosphoenolpyruvate H2O GTP CO2 GDP NAD NADH H+ NAD NADH H+ Pi H2O Pi H2O Q NADH QH2 NAD H+ Acetyl-CoA ATP HCO3- Malonyl-CoA ADP NADPH Acetyl-CoA CoA H2O NADP CO2 ATP H2O AMP H+ 3- Phosphoglyceric acid ATP ADP ADP Pyruvate ATP Magnesium Magnesium Magnesium Magnesium Potassium Magnesium Manganese Pyridoxal 5'-phosphate Manganese Long chain fatty acid Triglyceride cAMP CREB CRTC2 CRTC2 CREB PPi Citric Acid Cycle Oxidative Phosphorylation Triglyceride Synthesis & Storage Insulin resistance Magnesium Flavin Mononucleotide Fe3+ Magnesium Biotin Manganese Magnesium Calcium Metformin inhibits complex I of the respiratory chain, reducing ATP formation There is a high AMP:ADP ratio High AMP and fructose 2,6-bisphosphate inhibits fructose 1 bisphosphatase, preventing glucose formation Low concentrations of active PKA reduces inhibition on 6-phosphofructo-2- kinase/fructose-2,6- biphosphatase 1, preventing formation of glucose fructose-2,6-bisphosphate activates phosphofructokinase, bringing the reaction in the opposite direction to gluconeogenesis Metformin activates AMPK AMP inhibits adenylate cyclase, preventing the formation of cAMP High AMP activates AMP kinase AMPK inhibits acetyl-coA carboxylase, inhibiting fat synthesis and promoting fat oxidation instead, thus reducing hepatic lipid stores and enhancing hepatic insulin sensitivity AMPK inhibits the transcription factors necessary to produce G6P and PEP, needed for gluconeogenesis Low concentrations of active PKA occurs since PKA is activated by cAMP, and cAMP levels are low Mitochondria Inner membrane Outer membrane Intermembrane space Cytosol
Mitochondria PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PFKFB1 PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PFKFB1 PFKL FBP1 NDUFB11 NDUFB7 MT-ND1 MT-ND2 NDUFC2- KCTD14 MT-ND3 MT-ND4 MT-ND4L MT-ND5 MT-ND6 NDUFA1 NDUFA2 NDUFA3 NDUFA4 NDUFA5 NDUFA6 NDUFA7 NDUFA8 NDUFA9 NDUFA10 NDUFAB1 NDUFB1 NDUFB2 NDUFB3 NDUFB4 NDUFB5 NDUFB6 NDUFV3 NDUFA13 NDUFB11 NDUFA12 NDUFA4L2 NDUFS2 NDUFS3 NDUFV1 NDUFS4 NDUFS5 NDUFS6 NDUFS8 NDUFV2 NDUFB7 NDUFB8 NDUFB9 NDUFB10 NDUFC1 NDUFC2 NDUFS1 PRKAA1 PRKAG1 PRKAB1 ACACA ADCY10 GCGR GCG PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A SIK2 PDE4B PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PKLR SLC2A2 SLC25A12 SLC25A11 SLC25A31 SLC22A1 GPI G6PC ALDOB TPI1 GPD1 ENO1 PCK1 MDH1 MDH1 GOT2 AK1 FASN PCK1 G6PC PGK1 PGAM1 D-Fructose 2,6- bisphosphate D-Fructose 2,6- bisphosphate Adenosine monophosphate 1,1- Dimethylbiguanide 1,1- Dimethylbiguanide Oxaloacetate NADH FADH Adenosine triphosphate D-Glucose D-Glucose L-Aspartic acid L-Aspartic acid L-Glutamic acid L-Glutamic acid Malate Malate Oxoglutaric acid Oxoglutaric acid Malate Oxaloacetate Oxaloacetate Hydrogen Ion Hydrogen Ion Adenosine triphosphate Adenosine diphosphate Adenosine diphosphate 1,1- Dimethylbiguanide Glucose 6-phosphate Fructose 6-phosphate Phosphate Water Fructose 1,6- bisphosphate Water Phosphate Adenosine triphosphate Adenosine diphosphate D- Glyceraldehyde 3-phosphate Dihydroxyacetone phosphate Phosphate NAD Glyceric acid 1,3-biphosphate NADH Hydrogen Ion 2- Phosphoglyceric acid Phosphoenolpyruvate Water Guanosine triphosphate Carbon dioxide Guanosine diphosphate NAD NADH Hydrogen Ion NAD NADH Hydrogen Ion Phosphate Water Phosphate Water Coenzyme Q10 NADH QH2 NAD Hydrogen Ion Acetyl-CoA Adenosine triphosphate Hydrogen carbonate Malonyl-CoA Adenosine diphosphate NADPH Acetyl-CoA Coenzyme A Water NADP Carbon dioxide Adenosine triphosphate Water Adenosine monophosphate Hydrogen Ion 3- Phosphoglyceric acid Adenosine triphosphate Adenosine diphosphate Adenosine diphosphate Pyruvate Adenosine triphosphate Long chain fatty acid Triglyceride cAMP CREB CRTC2 CRTC2 CREB Pyrophosphate Citric Acid Cycle Oxidative Phosphorylation Triglyceride Synthesis & Storage Insulin resistance
PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PFKFB1 PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PFKFB1 PFKL FBP1 NDUFB11 NDUFB7 MT-ND1 MT-ND2 NDUFC2- KCTD14 MT-ND3 MT-ND4 MT-ND4L MT-ND5 MT-ND6 NDUFA1 NDUFA2 NDUFA3 NDUFA4 NDUFA5 NDUFA6 NDUFA7 NDUFA8 NDUFA9 NDUFA10 NDUFAB1 NDUFB1 NDUFB2 NDUFB3 NDUFB4 NDUFB5 NDUFB6 NDUFV3 NDUFA13 NDUFB11 NDUFA12 NDUFA4L2 NDUFS2 NDUFS3 NDUFV1 NDUFS4 NDUFS5 NDUFS6 NDUFS8 NDUFV2 NDUFB7 NDUFB8 NDUFB9 NDUFB10 NDUFC1 NDUFC2 NDUFS1 PRKAA1 PRKAG1 PRKAB1 ACACA ADCY10 GCGR GCG PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A SIK2 PDE4B PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PKLR SLC2A2 SLC25A12 SLC25A11 SLC25A31 SLC22A1 GPI G6PC ALDOB TPI1 GPD1 ENO1 PCK1 MDH1 MDH1 GOT2 AK1 FASN PCK1 G6PC PGK1 PGAM1 Fru2,6P Fru2,6P AMP DMBG DMBG Oxalo NADH FADH2 ATP D-Glc D-Glc Asp Asp Glu Glu Malate Malate AKG AKG Malate Oxalo Oxalo H+ H+ ATP ADP ADP DMBG Gluc-6P Fru6P Pi H2O Fru1,6P H2O Pi ATP ADP Glyc3P Dhapp Pi NAD GlyABp NADH H+ 2-PPGA Phosp H2O GTP CO2 GDP NAD NADH H+ NAD NADH H+ Pi H2O Pi H2O Q NADH QH2 NAD H+ Ac-CoA ATP HCO3- MalyCoA ADP NADPH Ac-CoA CoA H2O NADP CO2 ATP H2O AMP H+ G3P ATP ADP ADP Pyruv ATP Mg2+ Mg2+ Mg2+ Mg2+ K+ Mg2+ Mn2+ Pyr-5'P Mn2+ L c f a TG cAMP CREB CRTC2 CRTC2 CREB PPi PW000005 Oxi Pho T S & S Ins res Mg2+ FlvnMnt Fe3+ Mg2+ Biotin Mn2+ Mg2+ Ca2+ Metformin inhibits complex I of the respiratory chain, reducing ATP formation There is a high AMP:ADP ratio High AMP and fructose 2,6-bisphosphate inhibits fructose 1 bisphosphatase, preventing glucose formation Low concentrations of active PKA reduces inhibition on 6-phosphofructo-2- kinase/fructose-2,6- biphosphatase 1, preventing formation of glucose fructose-2,6-bisphosphate activates phosphofructokinase, bringing the reaction in the opposite direction to gluconeogenesis Metformin activates AMPK AMP inhibits adenylate cyclase, preventing the formation of cAMP High AMP activates AMP kinase AMPK inhibits acetyl-coA carboxylase, inhibiting fat synthesis and promoting fat oxidation instead, thus reducing hepatic lipid stores and enhancing hepatic insulin sensitivity AMPK inhibits the transcription factors necessary to produce G6P and PEP, needed for gluconeogenesis Low concentrations of active PKA occurs since PKA is activated by cAMP, and cAMP levels are low Mitochondria Inner membrane Outer membrane Intermembrane space Cytosol
Mitochondria PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PFKFB1 PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PFKFB1 PFKL FBP1 NDUFB11 NDUFB7 MT-ND1 MT-ND2 NDUFC2- KCTD14 MT-ND3 MT-ND4 MT-ND4L MT-ND5 MT-ND6 NDUFA1 NDUFA2 NDUFA3 NDUFA4 NDUFA5 NDUFA6 NDUFA7 NDUFA8 NDUFA9 NDUFA10 NDUFAB1 NDUFB1 NDUFB2 NDUFB3 NDUFB4 NDUFB5 NDUFB6 NDUFV3 NDUFA13 NDUFB11 NDUFA12 NDUFA4L2 NDUFS2 NDUFS3 NDUFV1 NDUFS4 NDUFS5 NDUFS6 NDUFS8 NDUFV2 NDUFB7 NDUFB8 NDUFB9 NDUFB10 NDUFC1 NDUFC2 NDUFS1 PRKAA1 PRKAG1 PRKAB1 ACACA ADCY10 GCGR GCG PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A SIK2 PDE4B PRKACA PRKACB PRKAR1A PRKACG PRKAR1B PRKAR2B PRKAR2A PKLR SLC2A2 SLC25A12 SLC25A11 SLC25A31 SLC22A1 GPI G6PC ALDOB TPI1 GPD1 ENO1 PCK1 MDH1 MDH1 GOT2 AK1 FASN PCK1 G6PC PGK1 PGAM1 Fru2,6P Fru2,6P AMP DMBG DMBG Oxalo NADH FADH ATP D-Glc D-Glc Asp Asp Glu Glu Malate Malate AKG AKG Malate Oxalo Oxalo H+ H+ ATP ADP ADP DMBG Gluc-6P Fru6P Pi H2O Fru1,6P H2O Pi ATP ADP Glyc3P Dhapp Pi NAD GlyABp NADH H+ 2-PPGA Phosp H2O GTP CO2 GDP NAD NADH H+ NAD NADH H+ Pi H2O Pi H2O Coq NADH QH2 NAD H+ Ac-CoA ATP HCO3 MalyCoA ADP NADPH Ac-CoA CoA H2O NADP CO2 ATP H2O AMP H+ G3P ATP ADP ADP Pyruv ATP L c f a TG cAMP CREB CRTC2 CRTC2 CREB Ppi PW000005 Oxi Pho T S & S Ins res