http___en.wikipedia.org_wiki_Cholesterol_synthesis_1.xml
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Изопентенил пирофосфат Изопентенил пирофосфатът (IPP) е междинен метаболит в класическия, мевалонатен път, използван от организмите за синтеза на терпеноиди. IPP се синтезира от ацетил-КоА. В последствие IPP може да бъде изомеризиран до диметилалил пирофосфат от ензима изопентенил пирофосфат изомераза. IPP може да бъде синтезиран и по алтернативен немевалонатен път на изопреноиднен синтез, където той се образува от (E)-4-хидрокси-3-метил-бут-2-енил пирофосфат (HMB-PP) от ензима HMB-PP редуктаза (LytB, IspH). Немевалонатният път се използва от някои бактерии, апикомплексни протозои като маларийноя плазмодий и пластидите на растенията.
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Mevalonate pathway The mevalonate pathway or HMG-CoA reductase pathway or mevalonate-dependent (MAD) route or isoprenoid pathway, is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria.[1] It is important for the production of dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP), which serve as the basis for the biosynthesis of molecules used in processes as diverse as terpenoid synthesis, protein prenylation, cell membrane maintenance, hormones, protein anchoring, and N-glycosylation. It is also a part of steroid biosynthesis.[2] Contents Regulation and feedback[edit] Several key enzymes can be activated through DNA transcriptional regulation on activation of SREBP (sterol regulatory element-binding protein-1 and -2). This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the LDL-receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation. - For more information on regulation, see HMG-CoA reductase Pharmacology[edit] A number of drugs target the mevalonate pathway: - Statins (used to decrease cholesterol levels); - Bisphosphonates (used to treat various bone-degenerative diseases) Alternative[edit] Plants and apicomplexan protozoa such as malaria parasites have the ability to produce their isoprenoids (terpenoids) using an additional alternative pathway called the methylerythritol phosphate (MEP) or non-mevalonate pathway, which takes place in their plastids. In addition, most bacteria including important pathogens, such as Mycobacterium tuberculosis, synthesize IPP and DMAPP via the non-mevalonate pathway instead. Reactions[edit] References[edit] - ^ Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th ed. New York: W.H. Freeman. xxxviii, 974, [976] (various pagings). - ^ Wiemer, AJ; Hohl, RJ; Wiemer, DF (June 2009). "The intermediate enzymes of isoprenoid metabolism as anticancer targets.". Anti-cancer agents in medicinal chemistry 9 (5): 526–42. External links[edit] - Rensselaer Polytechnic Institute page on cholesterol synthesis (including regulation)