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Aulani "Biokimia Enzim" Presentasi 10
Enzyme Phosphorylation
Aulanni’amBiochemistry LaboratoryChemistry DepartmentBrawijaya University
Aulani "Biokimia Enzim" Presentasi 10
Phosphorylation
ConformationalChangedephosphorylastion
Phosphatase
P
Protein
OH
SerSer Thr Tyr (His)
Active Inactive
Inactive Active
Glycogen phosphorylase b Glycogen phosphorylase a
Fischer, Kreb (1978)
Kinasephosphorylation
Aulani "Biokimia Enzim" Presentasi 10
Regulation of Blood Sugar
High blood sugarHigh blood sugar Insulin
Pancreas Glycogen Glucose
Decrease
Glycogen synthase
IncreaseIncrease
Hormone
Signal TransductionSignal Transduction
BloodLiverLiver
Low blood sugar Glucagon
GTP-protein-linked receptor
Tyrosine-kinase-linked receptor
Glycogen phosphorylase
Cori & Cori (1947)
Aulani "Biokimia Enzim" Presentasi 10
Rapid Response to Blood Sugar Concentration
Glycogen phosphorylase Glycogen synthaseE
nzym
e ac
tivity
0 2 4 6 8Time (min)
葡萄
糖
Very rapidly → Not controlled in gene level
Aulani "Biokimia Enzim" Presentasi 10
Glycogen Phosphorylase, GP
Glycogen
n n-1
Glc-1-P → Glc-6-P → Glycolysis
Glycogenphosphorylase a*
Phos
phat
ase
GPkinase
Glycogenphosphorylase b
(inactive)
ATP
Proteinkinase A
cAMP
Phosphorylase
+
+
AMP (+)ATP (-)Glc-6-P (-)
Glucose (-)Caffeine (-)
P
R
T6.2
6.3
6.4
P
P
Juang RH (2004) BCbasics
Aulani "Biokimia Enzim" Presentasi 10
cAMP Controls Protein Kinase A Activity
R C
R C
R
RA
A
A
A
AA
A
A
C
C
Regulatorysubunits
Catalyticsubunits
cAMPActive kinase
C
CREB
CREB
P
Nucleus
Activation
Geneexpression
DNA
Alb
ert
s e
t a
l (2
00
2)
Mo
lecu
lar
Bio
log
y o
f th
e C
ell
(4e
) p
. 8
57
, 8
58
Aulani "Biokimia Enzim" Presentasi 10
G protein
cAMP Is the Second Messenger
Glycogen Glc-1-P
PGP1 aGP b
PGP KinaseGP Kinase
Protein Kinase AProtein Kinase A
cAMPATP
Cyclase G protein
Adenylate cyclase
A Cyclic AMP (second messenger)
GP kinase
GP
ReceptorGlucagonSutherland (1971)
Cascade
Inactive
Active
Jua
ng
RH
(2
00
4)
BC
ba
sics
Aulani "Biokimia Enzim" Presentasi 10
SH2domain
Receptors on Cell Membrane
G protein
GDP
+ Signal
-GDP+GTP
GDP
GTP
GTP
Adenylate cyclase
+ Signal
ActivationP
ProteinPhosphatase
GlycogenSynthase
GlycogenSynthase P
active
Insulin
P P
PP kinase
Glucagon
A
G-protein-linked Receptor
Enzyme-linked ReceptorThe third group: Ion-channel-linked Receptor
Gilman, Rodbell (1994)
Glycogen breadkdown
Glycogen synthesis
Jua
ng
RH
(2
00
4)
BC
ba
sics
Aulani "Biokimia Enzim" Presentasi 10
P
P
A
GP kinase
GP kinase
GP a
GP b
Glycogen synthase
Glycogen synthase P
Protein phosphatase-1
Protein phosphatase-1
Protein phosphatase inhibitor-1
Protein phosphatase inhibitor-1
Glycogen
PKA
P
active
inactive
PhosphataseG
luca
gon
Adapted from Kleinsmith & Kish (1995) Principles of Cell and Molecular Biology (2e) p.217
Aulani "Biokimia Enzim" Presentasi 10
Signal Transduction
Receptor
Hormone Signal
G
Cyclase
Transducer
Effector Enzyme
Effector
Effect
各種荷爾蒙
各種接受體
不同的 G-protein
各種關鍵酵素
各種信息分子
各種效應Juang RH (2004) BCbasics