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

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

PKA cAMP Phosphorylase kinase Glycogen synthase PP1 I-1 PP1 Phos GS Glucagon receptor (Gs) Liver PFK2 FBPase F 2,6 bisP PK Glycolysis Gluconeogenesis Phosphorylase Glycogenolysis Glucose export

Epinephrine/Adrenalin Epinephrine: R = CH 3 Nor-epinephrine: R = H Where: adrenal medula When: stress – release of AcCholine by neurons stimulates chromaffin cells of adrenal medula to release adrenalin Receptors:  liver  liver and muscle (cAMP) Effect: liver increased glycogenolysis, gluconeogenesis muscle inclreased glycogenolysis, glycolysis

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

PKA cAMP Phosphorylase kinase Glycogen synthase PP1 I-1 PP1 Phos GS Adrenalin:  -receptor (Gs) Muscle F 2,6 bisP Glycolysis Phosphorylase Glycogenolysis FBPase Heart muscle Note: muscle isoform of PK is not phosphorylated by PKA

Insulin What: dimeric polypeptide 21 and 31 amino acids linked by S-S Where:  cells of pancreas (note:  cells contain GluT2) When: post absorptive state

Insulin receptor What: tetrameric (2 , 2  ), transmembrane tyrosine kinase Where: liver, muscle, adipocytes Effect: muscle – translocation of GluT4 increased glycogenesis liver: increased glycogenesis, increased glycolysis See figures 9-45 and 9-46 Horton

ISPK IRTK Glycogen synthase kinase Phos GS Insulin Liver PK PDH F 2,6 bisP Glycolysis Glycogen synthase Glycogenesis Several steps Several steps Phosphatase AcCoA (for biosynthetic purposes PFK2

ISPK IRTK Phos GS Insulin Muscle Several steps Several steps Phosphatase Translocation of GluT4 Glucose uptake Glycogenesis G6P

Summary of regulation of carbohydrate metabolism 1.Regulation by energy charge or metabolic intermediates Hexokinase G6P Glucokinase F6P (with regulatory protein) PFK1 ATP, citrate; AMP, F2,6 bisP PK ATP, F1,6 bisP PDH AcCoA, NADH F-1,6 bis Pase citrate, AMP, F2,6,bisP Pyruvate carboxylase AcCoA Isocitrate dehydrogenase NADH Phosphorylase b AMP (muscle), G6P, ATP Glycogen synthase b G6P 2. Regulation by phosphorylation PFK2: 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” GluT 2 liver, pancreas Glucokinase liver Phosphorylase a/PP1