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Glucagon

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increased glycogenesis. liver: increased glycogenesis, increased glycolysis ... Glycogenesis. G6P. Summary of regulation of carbohydrate metabolism ... – PowerPoint PPT presentation

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Title: Glucagon


1
Glucagon
What 29 amino acid peptide Where a cells of
pancreas When low blood glucose in response
to adrenalin (stress)
2
Glucagon receptor
What 7 transmembrane, G protein
coupled Where liver, adipocytes, and
elsewhere (brain, pancreas a cells) Effect
increased production of cAMP liver increased
glyogenolysis and gluconeogenesis adipocytes
increased lipolysis
3
Glucagon receptor (Gs)
cAMP
Liver
I-1
Phos
PP1
PKA
GS
PP1
PFK2
F 2,6 bisP
Phosphorylase kinase
Glycogen synthase
FBPase
PK
Phosphorylase
Glycolysis
Glucose export
Glycogenolysis
Gluconeogenesis
4
Epinephrine/Adrenalin
Epinephrine R CH3
Nor-epinephrine R H
Where adrenal medula When stress release
of AcCholine by neurons stimulates chromaffin
cells of adrenal medula to release adrenalin
Receptors a liver b liver and muscle
(cAMP)
Effect liver increased glycogenolysis,
gluconeogenesis muscle inclreased
glycogenolysis, glycolysis
5
Adrenalin a1-receptor (Gq)
liver
Ca2
PKC
Insulin receptor
Glycogen synthase
Phosphorylase kinase
Glycogenesis
Phosphorylase
Glycogenolysis
Epinephrine R CH3
Nor-epinephrine R H
6
Adrenalin b-receptor (Gs)
Muscle
cAMP
Phos
I-1
PP1
PKA
GS
PP1
FBPase
F 2,6 bisP
Phosphorylase kinase
Glycogen synthase
Heart muscle
Glycolysis
Phosphorylase
Note muscle isoform of PK is not
phosphorylated by PKA
Glycogenolysis
7
Insulin
What dimeric polypeptide 21 and 31 amino acids
linked by S-S Where b cells of pancreas
(note b cells contain GluT2) When post
absorptive state
8
Insulin receptor
What tetrameric (2a, 2b), 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
9
Insulin
IRTK
Liver
Several steps
Phos
Several steps
ISPK
Phosphatase
GS
PK
Glycogen synthase kinase
PFK2
F 2,6 bisP
PDH
Glycogen synthase
AcCoA (for biosynthetic purposes
Glycolysis
Glycogenesis
10
Insulin
IRTK
Muscle
Several steps
Phos
Several steps
ISPK
Phosphatase
GS
Translocation of GluT4
Glycogenesis
G6P
Glucose uptake
11
Summary of regulation of carbohydrate metabolism
  • 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

12
  • 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
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