萜类化合物合成途.ppt

Long-term regulation is by varied formation and degradation of HMG-CoA Reductase and other enzymes of the pathway for synthesis of cholesterol. Regulated proteolysis of HMG-CoA Reductase: Degradation of HMG-CoA Reductase is stimulated by cholesterol, oxidized derivatives of cholesterol, mevalonate, farnesol (dephosphorylated farnesyl pyrophosphate). HMG-CoA Reductase includes a transmembrane sterol-sensing domain that has a role in activating degradation of the enzyme via the proteasome (proteasome to be discussed later). Regulated transcription: A family of transcription factors designated SREBP (sterol regulatory element binding proteins) regulate synthesis of cholesterol and fatty acids. Of these, SREBP-2 mainly regulates cholesterol synthesis. (SREBP-1c mainly regulates fatty acid synthesis.) When sterol levels are low, SREBP-2 is released by cleavage of a membrane-bound precursor protein. SREBP-2 activates transcription of genes for HMG-CoA Reductase and other enzymes of the pathway for cholesterol synthesis. MVA pathway and Non-MVA pathway Isoprenoids pathway One of the basic pathways exist in organisms MEP pathway in plants and bacteria MVA pathway in yeast and animals Products from Isoprenoids pathway Drugs: taxol, artemisinin and so on Biofuels: farnesol, farnesene, terpene-based biofuels Materials: Isoprenoid → rubber MEP pathway in E. coli DXS: the first, rate-limiting step in MEP pathway thiamin diphosphate-dependent reaction Also involved in pyridoxal 5-phosphate and thiamine biosynthesis pathways DXR: the first committed step in MEP pathway NADPH-dependent, and required a bivalent metal cofactor IspD: CTP-dependent IspE: ATP-dependent IspF: Mn2+or Mg2+ dependent One Zn2+ is bound at each active site IspG: depends on as-yet unidentified additional proteins, most likely involved in the oxidation portion of the reaction In vitro reconstitution of IspH functions requires the presence of a reducing system, such as flav