Glucagon What 29 amino acid peptide Where a

Glucagon What: 29 amino acid peptide Where: a cells of pancreas When: low blood glucose in response to adrenalin (stress)

Glucagon receptor What: 7 transmembrane, G protein coupled Where: liver, adipocytes, and elsewhere (brain, pancreas a cells) Effect: increased production of c. AMP liver: increased glyogenolysis and gluconeogenesis adipocytes: increased lipolysis

Glucagon receptor (Gs) Liver c. AMP I-1 PKA PP 1 GS PP 1 PFK 2 Phosphorylase kinase Glycogen synthase Phos F 2, 6 bis. P FBPase PK Phosphorylase Glycogenolysis Glucose export Glycolysis Gluconeogenesis

Epinephrine/Adrenalin Epinephrine: R = CH 3 Nor-epinephrine: R = H Where: adrenal medula When: stress – release of Ac. Choline by neurons stimulates chromaffin cells of adrenal medula to release adrenalin Receptors: a liver b liver and muscle (c. AMP) Effect: liver increased glycogenolysis, gluconeogenesis muscle inclreased glycogenolysis, glycolysis

Adrenalin: a 1 -receptor (Gq) liver Ca 2+ Phosphorylase kinase Glycogen synthase PKC Insulin receptor Glycogenesis Phosphorylase Glycogenolysis Epinephrine: R = CH 3 Nor-epinephrine: R = H

Adrenalin: b-receptor (Gs) c. AMP Muscle I-1 PKA PP 1 GS PP 1 FBPase Phosphorylase kinase Glycogen synthase Phos F 2, 6 bis. P Heart muscle Glycolysis Phosphorylase Glycogenolysis Note: muscle isoform of PK is not phosphorylated by PKA

Insulin What: dimeric polypeptide 21 and 31 amino acids linked by S-S Where: b cells of pancreas (note: b cells contain Glu. T 2) When: post absorptive state

Insulin receptor What: tetrameric (2 a, 2 b), transmembrane tyrosine kinase Where: liver, muscle, adipocytes Effect: muscle – translocation of Glu. T 4 increased glycogenesis liver: increased glycogenesis, increased glycolysis See figures 9 -45 and 9 -46 Horton

Insulin Liver IRTK Several steps ISPK Phos Several steps Phosphatase GS PK Glycogen synthase kinase PFK 2 F 2, 6 bis. P PDH Glycogen synthase Glycogenesis Glycolysis Ac. Co. A (for biosynthetic purposes

Insulin Muscle IRTK Several steps ISPK Several steps Translocation of Glu. T 4 Glucose uptake Phosphatase GS Glycogenesis G 6 P

Summary of regulation of carbohydrate metabolism 1. Regulation by energy charge or metabolic intermediates • Hexokinase G 6 P • Glucokinase F 6 P (with regulatory protein) • PFK 1 ATP, citrate; AMP, F 2, 6 bis. P • PK ATP, F 1, 6 bis. P • PDH Ac. Co. A, NADH • F-1, 6 bis Pase citrate, AMP, F 2, 6, bis. P • Pyruvate carboxylase Ac. Co. A • Isocitrate dehydrogenase NADH • Phosphorylase b AMP (muscle), G 6 P, ATP • Glycogen synthase b G 6 P 2. Regulation by phosphorylation • PFK 2: inhibited in liver, activated in heart muscle • F-2, 6 -bis Pase: activated in liver • Pyruvate kinase: inhibited • Pyruvate dehydrogenase: inhibited (liver, PDH kinase and PDH phosphatase) • Phosphorylase activated by phosphorylase kinase • Glycogen synthase inhibited PKA and glycogen synthase kinase

3. Regulation by calcium - muscle • PDH phosphatase activated • Phosphoryae kinase activated • Isocitrate dehydrogenase activated • a-ketoglutarate dehydrogenase activated 4. Glucose “sensors” • Glu. T 2 liver, pancreas • Glucokinase liver • Phosphorylase a/PP 1