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

Aulani "Biokimia Enzim" Presentasi 10