![\"\"](\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/Lipid38.png\")
<\/a>Statins<\/h2>\n<\/span>\n\n\nStatins are a class of drugs often prescribed for the treatment of hypercholesterolemia<\/strong> (increased blood cholesterol levels), in order to reduce the risk for cardiovascular disease, by inhibiting the production of endogenous cholesterol through the inhibition of the\u00a0HMG-CoA reductase<\/strong> enzyme\u00a0(Figure 1<\/strong>).<\/p>\n\n\n<\/span>\nHMG-CoA reductase<\/h2>\n<\/span>\n\n\nIt is in the membrane of the endoplasmic reticulum. There are several INSIGs (\u201cinsulin-induced genes\u201d) membrane proteins that are temporarily binding for high cholesterol levels to specific proteins of the membrane, including HMG-CoA reductase and SCAP.<\/p>\n\n\n\n
SCAP (Sterol regulatory element-binding protein cleavage activating protein) is a regulatory protein that is required for the proteolytic cleavage of the sterol regulatory element-binding protein (SREBP).<\/p>\n\n\n\n
INSIG binds to HMG-CoA reductase type complexes with proteins that produce ubiquitin (Ubq-ligase) and the extraction of the ubiquitylated protein. In high cholesterol levels, INSIG and its related proteins result in rapid proteasomal degradation of HMG-CoA reductase in the cytoplasm. Thus, the cholesterol-synthesizing capacity of the cell (e.g., liver cell) decreases.<\/p>\n\n\n\n
![\"\"](\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/Lipid39-1024x955.png\")
<\/a>Figure 2. Low level of cholesterol<\/strong><\/figcaption><\/figure><\/div>\n\n\n<\/span>\nThe role of the SREBP transcription factor<\/h2>\n<\/span>\n\n\nThe sterol response element-binding is also an ER membrane protein with the cytoplasmic domain and when it is cleaved by SCAP, it acts as a transcriptional factor and enhances the expression of genes that increase the cell\u2019s cholesterol content. Separated and nucleated SREBP induces the production of enzymes of LDL receptor and cholesterol synthesis (e.g. HMG-CoA reductase) (Figure 2).<\/p>\n\n\n\n
![\"\"](\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/Lipid40-1024x482.png\")
<\/a>Figure 3. High cholesterol level<\/strong><\/figcaption><\/figure><\/div>\n\n\n\nSREBP binds to the \u201cSREBP cleavage-activating protein\u201d (SCAP) in the membrane of the endoplasmic reticulum and can be contacted with vesicular transport to Golgi, where SCAP, according to its name, promotes SREBP cleavage by proteases.<\/p>\n\n\n\n
However, this happens only at low cholesterol levels because otherwise an INSIG protein binds to SCAP and \u2013 as it never leaves the endoplasmic reticulum \u2013 prevents SCAP and SREBP from reaching Golgi (Figure 3<\/strong>).<\/p>\n\n\n<\/span>\nReferences<\/h2>\n<\/span>\n\n\nSnider MDS. Devlin\u2019s Textbook of Biochemistry with Clinical Correlations<\/strong>, the 8th Edition. John Wiley & Sons, Incorporated, 2020; 2019.<\/span> <\/p>\n\n\n\nhttps:\/\/www.rcsb.org\/3d-view\/1N7D\/1<\/a> (LDL receptor 3D structure)<\/p>\n<\/span>
HMG-CoA reductase<\/h2>\n<\/span>\n\n\nIt is in the membrane of the endoplasmic reticulum. There are several INSIGs (\u201cinsulin-induced genes\u201d) membrane proteins that are temporarily binding for high cholesterol levels to specific proteins of the membrane, including HMG-CoA reductase and SCAP.<\/p>\n\n\n\n
SCAP (Sterol regulatory element-binding protein cleavage activating protein) is a regulatory protein that is required for the proteolytic cleavage of the sterol regulatory element-binding protein (SREBP).<\/p>\n\n\n\n
INSIG binds to HMG-CoA reductase type complexes with proteins that produce ubiquitin (Ubq-ligase) and the extraction of the ubiquitylated protein. In high cholesterol levels, INSIG and its related proteins result in rapid proteasomal degradation of HMG-CoA reductase in the cytoplasm. Thus, the cholesterol-synthesizing capacity of the cell (e.g., liver cell) decreases.<\/p>\n\n\n\n
<\/a>Figure 2. Low level of cholesterol<\/strong><\/figcaption><\/figure><\/div>\n\n\n<\/span>\nThe role of the SREBP transcription factor<\/h2>\n<\/span>\n\n\nThe sterol response element-binding is also an ER membrane protein with the cytoplasmic domain and when it is cleaved by SCAP, it acts as a transcriptional factor and enhances the expression of genes that increase the cell\u2019s cholesterol content. Separated and nucleated SREBP induces the production of enzymes of LDL receptor and cholesterol synthesis (e.g. HMG-CoA reductase) (Figure 2).<\/p>\n\n\n\n
<\/a>Figure 3. High cholesterol level<\/strong><\/figcaption><\/figure><\/div>\n\n\n\nSREBP binds to the \u201cSREBP cleavage-activating protein\u201d (SCAP) in the membrane of the endoplasmic reticulum and can be contacted with vesicular transport to Golgi, where SCAP, according to its name, promotes SREBP cleavage by proteases.<\/p>\n\n\n\n
However, this happens only at low cholesterol levels because otherwise an INSIG protein binds to SCAP and \u2013 as it never leaves the endoplasmic reticulum \u2013 prevents SCAP and SREBP from reaching Golgi (Figure 3<\/strong>).<\/p>\n\n\n<\/span>\nReferences<\/h2>\n<\/span>\n\n\nSnider MDS. Devlin\u2019s Textbook of Biochemistry with Clinical Correlations<\/strong>, the 8th Edition. John Wiley & Sons, Incorporated, 2020; 2019.<\/span> <\/p>\n\n\n\nhttps:\/\/www.rcsb.org\/3d-view\/1N7D\/1<\/a> (LDL receptor 3D structure)<\/p>\n<\/span>
<\/a>The role of the SREBP transcription factor<\/h2>\n<\/span>\n\n\nThe sterol response element-binding is also an ER membrane protein with the cytoplasmic domain and when it is cleaved by SCAP, it acts as a transcriptional factor and enhances the expression of genes that increase the cell\u2019s cholesterol content. Separated and nucleated SREBP induces the production of enzymes of LDL receptor and cholesterol synthesis (e.g. HMG-CoA reductase) (Figure 2).<\/p>\n\n\n\n
<\/a>Figure 3. High cholesterol level<\/strong><\/figcaption><\/figure><\/div>\n\n\n\nSREBP binds to the \u201cSREBP cleavage-activating protein\u201d (SCAP) in the membrane of the endoplasmic reticulum and can be contacted with vesicular transport to Golgi, where SCAP, according to its name, promotes SREBP cleavage by proteases.<\/p>\n\n\n\n
However, this happens only at low cholesterol levels because otherwise an INSIG protein binds to SCAP and \u2013 as it never leaves the endoplasmic reticulum \u2013 prevents SCAP and SREBP from reaching Golgi (Figure 3<\/strong>).<\/p>\n\n\n<\/span>\nReferences<\/h2>\n<\/span>\n\n\nSnider MDS. Devlin\u2019s Textbook of Biochemistry with Clinical Correlations<\/strong>, the 8th Edition. John Wiley & Sons, Incorporated, 2020; 2019.<\/span> <\/p>\n\n\n\nhttps:\/\/www.rcsb.org\/3d-view\/1N7D\/1<\/a> (LDL receptor 3D structure)<\/p>\n<\/span>
<\/a>SREBP binds to the \u201cSREBP cleavage-activating protein\u201d (SCAP) in the membrane of the endoplasmic reticulum and can be contacted with vesicular transport to Golgi, where SCAP, according to its name, promotes SREBP cleavage by proteases.<\/p>\n\n\n\n
However, this happens only at low cholesterol levels because otherwise an INSIG protein binds to SCAP and \u2013 as it never leaves the endoplasmic reticulum \u2013 prevents SCAP and SREBP from reaching Golgi (Figure 3<\/strong>).<\/p>\n\n\n<\/span>\n Snider MDS. Devlin\u2019s Textbook of Biochemistry with Clinical Correlations<\/strong>, the 8th Edition. John Wiley & Sons, Incorporated, 2020; 2019.<\/span> <\/p>\n\n\n\n https:\/\/www.rcsb.org\/3d-view\/1N7D\/1<\/a> (LDL receptor 3D structure)<\/p>\n<\/span>References<\/h2>\n<\/span>\n\n\n