No 21
Introduction to exercise no 22. Metabolism of cholesterol and lipoproteinsdr Janina ZawiertaObligatory learning material:Chapter 18: subchapters: I?; II?; III; IV; V; VI?; VIII?; Fig. 18.29Obligatory: knowledge of the course of metabolic pathways of cholesterol, bile acids, lipoproteins - reactions, enzymes, cofactors, regulationIssues to consider when self-learning:1. Cholesterol is one of the metabolites that is a risk factor for atherosclerosis. So think about why it is synthesized in our body and why do we take it in foods?2. What is the role of phytosterols in regulating cholesterol absorption?3. Note the tissue and subcellular location of cholesterol synthesis4. What metabolite is the basic substrate for cholesterol biosynthesis and what are the necessary cofactors for this process?5. What is the function of hepatic HMG-CoA synthase?6. Pay attention to the three characteristic stages of cholesterol synthesis: formation of mevalonate, squalene formation, cyclization of squalene to cholesterol. What are characteristic reactions of these stages?7. HMG-CoA reductase is a rate-limiting enzyme of cholesterol synthesis. Pay attention to the various mechanisms regulating the activity of this enzyme - the action of SREBP-2 and INSIG proteins, hormones, phosphorylation and dephosphorylation. What is the role of insulin in these mechanisms - on the one hand, it leads to the activation of HMG-CoA reductase, on the other hand, it increases the expression of genes for INSIG proteins? What is the mechanism of action of cholesterol synthesis lowering drugs?8. Can cholesterol be degraded to CO2 and H2O in the body?9. How can excess cholesterol be removed from the body?10. What are the characteristic reactions of the bile acid synthesis? Which of them is the rate-limiting step? What is the meaning of bile acid coupling reactions? What is the role of intestinal bacteria in bile acid metabolism?11. What is the difference between primary and secondary bile acids? Which of them are present in bile?12. How can enterohepatic circulation affect the regulation of bile acid synthesis and cholesterol homeostasis?13. What is the mechanism of action of cholestyramine or dietary fiber on blood cholesterol level?14. What health disorders result from a deficiency of bile salts and phospholipids in bile?15. Consider why the liver, among many body tissues, plays the most important role in regulating cholesterol homeostasis in the body?16. Note the classification and differences in the structure of lipoprotein particles of different classes. Can this affect their metabolic functions?17. In what tissue and in what state (fed or fasting) are chylomicrons synthesized? What is the difference between a newly secreted particle and a functionally mature one? What is the plasma metabolism of chylomicrons for? What tissues use fatty acids and glycerol released from TAG chylomicrons, and what is the fate of dietary cholesterol?18. What is the difference between VLDL metabolism and chylomicron metabolism? When are they synthesized?19. Lipoproteins transport lipid material between tissues. Despite this, individual classes have slightly different functions: chylomicrons transport food fats to many tissues and cholesterol to the liver, VLDL transport endogenous fats to extrahepatic tissues, LDL are the only lipoprotein supplying cholesterol to extrahepatic tissues. HDL perform special functions: they take part in reverse cholesterol transport (from tissues and lipoproteins to the liver), are apolipoprotein donors and acceptors, and are a cholesterol esterification site.20. Note the role of individual apolipoproteins in lipoprotein metabolism. Which of them perform structural functions, which are activators or inhibitors of enzymes, which are receptor ligands?21. Consider whether you can write the correct reactions for lipoprotein lipases and LCAT and determine their role in lipoprotein metabolism. Do you know how LPL differs from hepatic lipase? How is heart LPL different from LPL of fat tissue and how does it have metabolic significance? What is the meaning of plasma cholesterol esterification?22. Many different lipoprotein receptors function in lipoprotein metabolism. Do you know their tissue location? Do you know the mechanism of lipoprotein or cholesterol uptake by these receptors?23. Try to compare the function of two cholesterol-rich lipoprotein classes - LDL and HDL?24. Note the characteristic Lp (a) lipoprotein. When do we find its presence in plasma?25. Try to summarize the role of the liver in lipoprotein and cholesterol metabolism ................
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