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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the ''PCSK9'' gene in humans.〔 PCSK9 binds to the receptor for low-density lipoprotein (LDL) cholesterol. In the liver, the LDL receptor removes LDL cholesterol from the blood. When PCSK9 binds to the LDL receptor, the receptor is broken down and can no longer remove LDL cholesterol from the blood. If PCSK9 is blocked, more LDL receptors will be present on the surface of the liver and will remove more LDL cholesterol from the blood. Therefore, blocking PCSK9 can lower blood cholesterol levels. Similar genes (orthologs) are found across many species. PCSK9 is inactive when first synthesized, because a section of peptide chains blocks their activity; proprotein convertases remove that section to activate the enzyme.〔 PCSK9 has medical significance because it acts in cholesterol homeostasis. Drugs that can block PCSK9, thus lowering low-density lipoprotein cholesterol (LDL-C). The first two PCSK9 inhibitors, alirocumab and evolocumab, were approved by the U.S. Food and Drug Administration in 2015 for lowering cholesterol where statins and other drugs were insufficient. The manufacturers did not submit data to show that the drugs actually improved outcomes of cardiovascular disease, but they assumed that lowering cholesterol would improve cardiovascular disease.〔Reducing LDL with PCSK9 Inhibitors -- The Clinical Benefit of Lipid Drugs, DOI: 10.1056/NEJMp1508120〕 == Function == This gene encodes a proprotein convertase belonging to the proteinase K subfamily of the secretory subtilase family. The encoded protein is synthesized as a soluble zymogen that undergoes autocatalytic intramolecular processing in the endoplasmic reticulum. The protein may function as a proprotein convertase. This protein plays a major regulatory role in cholesterol homeostasis. PCSK9 binds to the epidermal growth factor-like repeat A (EGF-A) domain of the low-density lipoprotein receptor (LDLR), inducing LDLR degradation. Reduced LDLR levels result in decreased metabolism of LDL-C, which could lead to hypercholesterolemia.〔 PCSK9 may also have a role in the differentiation of cortical neurons.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「PCSK9」の詳細全文を読む スポンサード リンク
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