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Sterol
regulatory
element-binding
protein
cleavage-
activating
protein
Sterol
regulatory
element-binding
protein
cleavage-
activating
protein
Sterol
regulatory
element-binding
protein
cleavage-
activating
protein
3-Hydroxy-3-
methylglutaryl-
coenzyme A
reductase
Sterol
regulatory
element-binding
protein 1
Sterol
regulatory
element-binding
protein 1
Sterol
regulatory
element-binding
protein 1
Importin
subunit beta-1
Low-density
lipoprotein
receptor
Low-density
lipoprotein
receptor
Solute carrier
organic anion
transporter
family member
1B1
Sterol
regulatory
element-binding
protein 1
Insulin-induced
gene 1 protein
Insulin-induced
gene 1 protein
Sterol
regulatory
element-binding
protein
cleavage-
activating
protein
Membrane-bound
transcription
factor site-1
protease
Membrane-bound
transcription
factor site-2
protease
Acetyl-CoA
acetyltransferase,
cytosolic
Hydroxymethylglutaryl-
CoA synthase,
cytoplasmic
Sterol
regulatory
element-binding
protein 1
Atorvastatin
Acetyl-CoA
Mevalonic acid
Atorvastatin
Acetoacetyl-CoA
CoA
H
2
O
3-Hydroxy-3-
methylglutaryl-
CoA
CoA
H
+
CoA
NADP
H
+
NADPH
Calcium
Zinc
Low-density lipoprotein receptor
Promoter
Glycolysis
Cholesterol
Biosynthesis
Cholesterol
Binds reversibly to the
active site of the
rate-limiting enzyme in
cholesterol biosynthesis
INSIG no longer binds to the
SCAP-SREBP complex when
sterol concentrations are
low
SCAP-SREBP travels to the
Golgi apparatus from the ER
as cargo in COPII vesicles
Two proteases, , S1P and
S2P, sequentially cleave the
SCAP-SREBP complex,
releasing the mature form of
SREBP into the cytoplasm
SREBP translocates to the
nucleus
SREBP binds to the sterol
regulatory element (SRE)
present in the promoter
region of genes involved in
cholesterol uptake
The elevated amount of LDL-R
results in the binding of
more circulating free LDL
cholesterol
Nucleoplasm
Golgi Apparatus Membrane
Endoplasmic Reticulum
Membrane
Cytoplasm
Nucleus
Endoplasmic Reticulum
Golgi Apparatus
SCAP
SCAP
SCAP
HMGCR
SREBF1
SREBF1
SREBF1
KPNB1
LDLR
LDLR
SLCO1B1
SREBF1
INSIG1
INSIG1
SCAP
MBTPS1
MBTPS2
ACAT2
HMGCS1
SREBF1
Atorvastatin
Acetyl-CoA
Mevalonic acid
Atorvastatin
Acetoacetyl-CoA
Coenzyme A
Water
3-Hydroxy-3-
methylglutaryl-
CoA
Coenzyme A
Hydrogen Ion
Coenzyme A
NADP
Hydrogen Ion
NADPH
Low-density
lipoprotein
receptor
Promoter
Glycolysis
Cholesterol
Biosynthesis
Cholesterol
SCAP
SCAP
SCAP
HMGCR
SREBF1
SREBF1
SREBF1
KPNB1
LDLR
LDLR
SLCO1B1
SREBF1
INSIG1
INSIG1
SCAP
MBTPS1
MBTPS2
ACAT2
HMGCS1
SREBF1
atorva
Ac-CoA
Mva
atorva
ActaCoA
CoA
H
2
O
HMG-CoA
CoA
H
+
CoA
NADP
H
+
NADPH
Ca2+
Zinc
LDL-R
P
PW000146
Cho Bio
Lanol
Binds reversibly to the
active site of the
rate-limiting enzyme in
cholesterol biosynthesis
INSIG no longer binds to the
SCAP-SREBP complex when
sterol concentrations are
low
SCAP-SREBP travels to the
Golgi apparatus from the ER
as cargo in COPII vesicles
Two proteases, , S1P and
S2P, sequentially cleave the
SCAP-SREBP complex,
releasing the mature form of
SREBP into the cytoplasm
SREBP translocates to the
nucleus
SREBP binds to the sterol
regulatory element (SRE)
present in the promoter
region of genes involved in
cholesterol uptake
The elevated amount of LDL-R
results in the binding of
more circulating free LDL
cholesterol
Nucleoplasm
Golgi Apparatus Membrane
Endoplasmic Reticulum
Membrane
Cytoplasm