ENTRY ko04922 Pathway NAME Glucagon signaling pathway DESCRIPTION Glucagon is conventionally regarded as a counterregulatory hormone for insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. Glucagon also stimulates hepatic mitochondrial beta-oxidation to supply energy for glucose production. Glucagon performs its main effect via activation of adenylate cyclase. The adenylate-cyclase-derived cAMP activates protein kinase A (PKA), which then phosphorylates downstream targets, such as cAMP response element binding protein (CREB) and the bifunctional enzyme 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase (one of the isoforms being PFK/FBPase 1, encoded by PFKFB1). CLASS Organismal Systems; Endocrine system PATHWAY_MAP ko04922 Glucagon signaling pathway ORTHOLOGY K00016 LDH; L-lactate dehydrogenase [EC:1.1.1.27] K00161 PDHA; pyruvate dehydrogenase E1 component subunit alpha [EC:1.2.4.1] K00162 PDHB; pyruvate dehydrogenase E1 component subunit beta [EC:1.2.4.1] K00688 PYG, glgP; glycogen phosphorylase [EC:2.4.1.1] K00693 GYS; glycogen synthase [EC:2.4.1.11] K00850 pfkA, PFK; 6-phosphofructokinase 1 [EC:2.7.1.11] K00871 PHKG; phosphorylase kinase gamma subunit [EC:2.7.11.19] K00873 PK, pyk; pyruvate kinase [EC:2.7.1.40] K01084 G6PC; glucose-6-phosphatase [EC:3.1.3.9] K01596 E4.1.1.32, pckA, PCK; phosphoenolpyruvate carboxykinase (GTP) [EC:4.1.1.32] K01834 PGAM, gpmA; 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase [EC:5.4.2.11] K01946 ACACB; acetyl-CoA carboxylase / biotin carboxylase 2 [EC:6.4.1.2 6.3.4.14 2.1.3.15] K02183 CALM; calmodulin K03841 FBP; fructose-1,6-bisphosphatase I [EC:3.1.3.11] K04345 PKA; protein kinase A [EC:2.7.11.11] K04348 PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16] K04374 ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4 K04450 ATF2, CREBP1; cyclic AMP-dependent transcription factor ATF-2 K04456 AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1] K04498 EP300, CREBBP, KAT3; E1A/CREB-binding protein [EC:2.3.1.48] K04515 CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] K04583 GCGR; glucagon receptor K04632 GNAS; guanine nucleotide-binding protein G(s) subunit alpha K04634 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1 K04959 ITPR2; inositol 1,4,5-triphosphate receptor type 2 K04960 ITPR3; inositol 1,4,5-triphosphate receptor type 3 K05259 GCG; glucagon K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K05870 CREB1; cyclic AMP-responsive element-binding protein 1 K06268 PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit K07190 PHKA_B; phosphorylase kinase alpha/beta subunit K07198 PRKAA, AMPK; 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31] K07199 PRKAB; 5'-AMP-activated protein kinase, regulatory beta subunit K07200 PRKAG; 5'-AMP-activated protein kinase, regulatory gamma subunit K07201 FOXO1; forkhead box protein O1 K07202 PPARGC1A, PGC1A; alpha peroxisome proliferator-activated receptor gamma coactivator 1-alpha K07294 NR1C1, PPARA; peroxisome proliferator-activated receptor alpha K07299 SLC2A1, GLUT1; MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1 K07593 SLC2A2, GLUT2; MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 2 K08042 ADCY2; adenylate cyclase 2 [EC:4.6.1.1] K08765 CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [EC:2.3.1.21] K09047 CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5 K09048 CREB3; cyclic AMP-responsive element-binding protein 3 K11262 ACACA; acetyl-CoA carboxylase / biotin carboxylase 1 [EC:6.4.1.2 6.3.4.14 2.1.3.15] K11411 SIRT1, SIR2L1; NAD-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286] K11434 PRMT1; type I protein arginine methyltransferase [EC:2.1.1.319] K12407 GCK; glucokinase [EC:2.7.1.2] K13296 PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [EC:3.1.4.17] K15423 PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit [EC:3.1.3.16] K16311 SIK2; serine/threonine-protein kinase SIK2 [EC:2.7.11.1] K16333 CRTC2, TORC2; CREB-regulated transcription coactivator 2 K17491 SMEK, PPP4R3; protein phosphatase 4 regulatory subunit 3 K19008 SIK1; serine/threonine-protein kinase SIK1 [EC:2.7.11.1] K19028 PFKFB1; 6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 1 [EC:2.7.1.105 3.1.3.46] K19523 CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [EC:2.3.1.21] K19524 CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [EC:2.3.1.21] COMPOUND C00022 Pyruvate C00024 Acetyl-CoA C00026 2-Oxoglutarate C00031 D-Glucose C00036 Oxaloacetate C00040 Acyl-CoA C00042 Succinate C00074 Phosphoenolpyruvate C00076 Calcium cation C00083 Malonyl-CoA C00085 D-Fructose 6-phosphate C00103 D-Glucose 1-phosphate C00122 Fumarate C00149 (S)-Malate C00158 Citrate C00182 Glycogen C00186 (S)-Lactate C00197 3-Phospho-D-glycerate C00311 Isocitrate C00354 D-Fructose 1,6-bisphosphate C00575 3',5'-Cyclic AMP C00631 2-Phospho-D-glycerate C00665 beta-D-Fructose 2,6-bisphosphate C00668 alpha-D-Glucose 6-phosphate C01172 beta-D-Glucose 6-phosphate C01245 D-myo-Inositol 1,4,5-trisphosphate REFERENCE PMID:12626323 AUTHORS Jiang G, Zhang BB TITLE Glucagon and regulation of glucose metabolism. 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JOURNAL Nature 485:128-32 (2012) DOI:10.1038/nature10988 REL_PATHWAY ko00010 Glycolysis / Gluconeogenesis ko00020 Citrate cycle (TCA cycle) ko00061 Fatty acid biosynthesis ko00190 Oxidative phosphorylation ko04020 Calcium signaling pathway ko04024 cAMP signaling pathway ko04068 FoxO signaling pathway ko04910 Insulin signaling pathway ///