Karbohidrat Metabolizmasi

1
GLUCAGON AND ADRENALINE ACTION - REGULATION OF
METABOLISM
2
Overview of fuel mobilisation in different tissues
LIVER
BRAIN
glycogenolysis
glucose
glucose
glycogen
glucose
gluconeogenesis
glycerol
CO2 H2O
AA
FA glycerol
glycogen
AA
FA
lipolysis
triglyceride
protein
CO2 H2O
ADIPOSE TISSUE
MUSCLE
FA fatty acids AA amino acids
Glucagon acts on liver to maintain blood glucose
levels (gluconeogenesis and glycogenolysis) Adrena
line acts on muscle glycogenolysis liver -
glycogenolysis adipose
lipolysis tissue
3
Regulation of glycogenolysis by glucagon and
adrenaline (remember also allosteric regulation
see Prof. Denton's lectures)
glycogen
GLYCOGEN SYNTHASE
PHOSPHORYLASE
glucose-1-P
4
PKA acts on phosphorylase kinase
5
PKA directly phosphorylates glycogen synthase
PKA
glycogen synthase a
glycogen synthase b
(inactive)
6
Protein phosphatase-1 is inactivated by an
inhibitor protein
PKA
ATP
ADP
PP-1
Pi
AMPLIFICATION occurs by simultaneous activation
of glycogen breakdown and inhibition of glycogen
synthesis
7
1500
30-fold increase in phosphorylase kinase activity
1000
activity
500
10-7
10-5
10-4
10-6
Ca2 M
8
Glucagon stimulates gluconeogenesis in liver -
role of F2,6,P2
PC and PEPCK subject to long-term regulation
amino acids, lactate
pyruvate
PC
glycerol
oxaloacetate
PK
PKA
PEPCK
phosphoenol pyruvate
9
Adrenaline stimulates glycolysis in muscle (heart)
10
Regulation of triglyceride breakdown (lipolysis)
11
Net effect of adrenaline.. (Fight-or-flight
response)

• glycogen breakdown
• triglyceride breakdown
• stimulate glucagon release
• inhibit insulin release