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HMG-CoA reductase Sterol regulatory element-binding protein 1 Sterol regulatory element-binding protein cleavage- activating protein Sterol regulatory element-binding protein 1 Sterol regulatory element-binding protein cleavage- activating protein Sterol regulatory element-binding protein 1 Sterol regulatory element-binding protein 1 Importin subunit beta-1 Low-density lipoprotein receptor Low-density lipoprotein receptor 3-Hydroxy-3- methylglutaryl- CoA Transporter Solute carrier organic anion transporter family member 1B1 Acetyl-CoA acetyltransferase, mitochondrial Hydroxymethylglutaryl- CoA synthase, cytoplasmic 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 Sterol regulatory element-binding protein cleavage- activating protein Pitavastatin Acetyl-CoA Mevalonate Cholesterol 3-Hydroxy-3-methylglutaryl-CoA 3-Hydroxy-3-methylglutaryl-CoA Pitavastatin Pitavastatin Acetoacetyl-CoA NADPH H+ NADP CoA Calcium Zinc Low-density lipoprotein receptor Promoter Glycolysis Cholesterol Biosynthesis Endoplasmic Reticulum Golgi Apparatus Nucleus Hepatocyte Pitavastatin inhibits HMG-CoA Reductase by binding reversibly to the active site, thus stopping any further cholersterol biosynthesis. Inhibition by pitavastatin reduces cholesterol levels, due to these decreased levels INSIG no longer binds to SCAP-SREBP complex. S1P and S2P proteases cleaves the SCAP-SREBP complex to release the mature form of SREBP into the cytoplasm. SREBP is transported into the nucleus and binds to sterol regulatory element (SRE) found within the promoter. This element is responsible for expression of cholesterol receptors and uptake. Cytosol The binding of SREBP to SRE up regulates the expression of low density lipoprotein receptor on the cell membrane surface. Increased low density lipoprotein receptors binds circulating low density lipoprotein cholesterol therefore decreasing the LDL cholesterol levels in the body. SCAP-SREBP complex is then transported from the endoplasmic reticulum to the golgi apparatus via COPII vesicles. COPII Vesicle Pitavastatin is taken orally and absorbed through the gastrointestinal system into the blood and travels to the liver. Blood vessel Liver
Endoplasmic Reticulum Nucleus Golgi Apparatus HMGCLL1 SREBF1 SCAP SREBF1 SCAP SREBF1 SREBF1 KPNB1 LDLR LDLR Unknown SLCO1B1 ACAT1 HMGCS1 SREBF1 INSIG1 INSIG1 SCAP MBTPS1 MBTPS2 SCAP Pitavastatin Acetyl-CoA Mevalonate Cholesterol 3-Hydroxy-3- methylglutaryl- CoA 3-Hydroxy-3- methylglutaryl- CoA Pitavastatin Pitavastatin Acetoacetyl-CoA NADPH Hydrogen Ion NADP Coenzyme A Low-density lipoprotein receptor Promoter Glycolysis Cholesterol Biosynthesis
HMGCLL1 SREBF1 SCAP SREBF1 SCAP SREBF1 SREBF1 KPNB1 LDLR LDLR SLCO1B1 ACAT1 HMGCS1 SREBF1 INSIG1 INSIG1 SCAP MBTPS1 MBTPS2 SCAP NK 104 Ac-CoA Meval Lanol HMG-CoA HMG-CoA NK 104 NK 104 ActaCoA NADPH H+ NADP CoA Ca2+ Zinc LDL-R P PW000146 Cho Bio Endoplasmic Reticulum Golgi Apparatus Nucleus Hepatocyte Pitavastatin inhibits HMG-CoA Reductase by binding reversibly to the active site, thus stopping any further cholersterol biosynthesis. Inhibition by pitavastatin reduces cholesterol levels, due to these decreased levels INSIG no longer binds to SCAP-SREBP complex. S1P and S2P proteases cleaves the SCAP-SREBP complex to release the mature form of SREBP into the cytoplasm. SREBP is transported into the nucleus and binds to sterol regulatory element (SRE) found within the promoter. This element is responsible for expression of cholesterol receptors and uptake. Cytosol The binding of SREBP to SRE up regulates the expression of low density lipoprotein receptor on the cell membrane surface. Increased low density lipoprotein receptors binds circulating low density lipoprotein cholesterol therefore decreasing the LDL cholesterol levels in the body. SCAP-SREBP complex is then transported from the endoplasmic reticulum to the golgi apparatus via COPII vesicles. COPII Vesicle Pitavastatin is taken orally and absorbed through the gastrointestinal system into the blood and travels to the liver. Blood vessel Liver
Endoplasmic Reticulum Nucleus Golgi Apparatus HMGCLL1 SREBF1 SCAP SREBF1 SCAP SREBF1 SREBF1 KPNB1 LDLR LDLR SLCO1B1 ACAT1 HMGCS1 SREBF1 INSIG1 INSIG1 SCAP MBTPS1 MBTPS2 SCAP NK 104 Ac-CoA Meval Lanol HMG-CoA HMG-CoA NK 104 NK 104 ActaCoA NADPH H+ NADP CoA LDL-R P PW000146 Cho Bio