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Enzyme Phosphorylation
Aulanni’am
Biochemistry Laboratory
Chemistry Department
Brawijaya University
Aulani "Biokimia Enzim"
Presentasi 10
Phosphorylation
Fischer, Kreb (1978)
Ser Thr Tyr (His)
OH
Protein
Kinase
phosphorylation
dephosphorylastion
Phosphatase
Glycogen phosphorylase b
P
Conformational
Change
Glycogen phosphorylase a
Inactive
Active
Active
Inactive
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Regulation of Blood Sugar
Cori & Cori (1947)
Signal Transduction
Decrease
Tyrosine-kinase-linked receptor
High blood sugar Insulin
Liver
Blood Pancreas Hormone Glycogen
Low blood sugar Glucagon
Glycogen
synthase
Glucose
Glycogen
phosphorylase
GTP-protein-linked receptor
Increase
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Rapid Response to Blood Sugar Concentration
Enzyme activity
Glycogen phosphorylase
Very rapidly →
Glycogen synthase
葡
萄
糖
0
2
4
6
Time (min)
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8
Not controlled in gene level
Glycogen Phosphorylase, GP
Glc-1-P → Glc-6-P → Glycolysis
Glycogen
Glycogen
phosphorylase a*
P
Phosphorylase
Protein
kinase A
+
6.2
+
cAMP
6.3
P
GP
kinase
ATP
Phosphatase
n
P
R
Glucose (-)
Caffeine (-)
T
6.4
Glycogen
phosphorylase b
(inactive)
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n-1
AMP (+)
ATP (-)
Glc-6-P (-)
Juang RH (2004) BCbasics
cAMP Controls Protein Kinase A Activity
A
A
A
Active kinase
cAMP
A
R
R
C
A
C
A
A
Catalytic
subunits
Nucleus
A
R
R
C
CREB
Activation
P
C
Gene
expression
CREB
DNA
C
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Presentasi 10
Alberts et al (2002) Molecular Biology of the Cell (4e) p. 857, 858
Regulatory
subunits
cAMP Is the Second Messenger
Sutherland (1971)
Adenylate cyclase
Cyclase G protein
ATP
cAMP
Protein Kinase A
Glucagon
Receptor
A
G protein
Cyclic AMP (second messenger)
Protein Kinase A
Cascade
GP Kinase
GP Kinase
P
GP b
GP1 a
Inactive
Active
P
GP
Glycogen
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Presentasi 10
Glc-1-P
Juang RH (2004) BCbasics
GP kinase
Receptors on Cell Membrane
Gilman, Rodbell (1994)
Adenylate cyclase
a
a
GTP
GTP
G-protein-linked Receptor
Glucagon
+ Signal
-GDP
+GTP
a
g
b
GDP
a
GDP
b
g
G protein
Glycogen breadkdown
The third group:
Ion-channel-linked Receptor
Glycogen
Synthase
active
Glycogen
Synthase
P
P
Enzyme-linked Receptor
a
Insulin
+ Signal
Activation P
Protein
Phosphatase
P
kinase
P
Glycogen synthesis
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P
SH2
domain
b
Juang RH (2004) BCbasics
A
Phosphatase
GP kinase
GP b
Glucagon
GP kinase P
GP a
Glycogen synthase
Glycogen synthase
A
PKA
P
Glycogen
Protein phosphatase-1
Protein phosphatase-1 P
Protein phosphatase inhibitor-1
active
inactive
Protein phosphatase inhibitor-1
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P
Adapted from Kleinsmith & Kish (1995) Principles of Cell and Molecular Biology (2e) p.217
Signal Transduction
各種荷爾蒙
Hormone Signal
各種接受體
Receptor
不同的 G-protein
各種關鍵酵素
G
Cyclase
Transducer
Effector Enzyme
各種信息分子
Effector
各種效應
Effect
Aulani "Biokimia Enzim"
Presentasi 10
Juang RH (2004) BCbasics
Aulani "Biokimia Enzim"
Presentasi 10