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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 H2O 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 H2O 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