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Chol Syn & Met
USCSOM: Cholesterol Synthesis and Metabolism
| Question | Answer |
|---|---|
| What is the storage form of cholesterol? | Cholesterol ester |
| Cholesterol is a precursor of what (2) things | Steroid hormones & Vitamin D synthesis |
| Where does Cholesterol synthesis occur? | cytosol |
| What are the energy requirements for Ch synthesis? | 18 acetyl CoA, 18 ATP, 18 NADPH |
| What makes up HMG-CoA? | 3 acetyl CoA |
| What does HMG-CoA reductase do? What is required? | Catalyzes HMG-CoA to Mevalonate; 2NADPH |
| IPPP | Isoprene Pyrophosphate, Isopentyl-PPi |
| DMAPP | Dimethyl-allyl-PPi; an isomerase of IPPP |
| What forms Squalene? | 6 Isoprene-Phosphate; 2 Farnesyl-PPi |
| What forms Geranyl-PPi? | IPPP + DMAPP head-to-tail |
| What forms Farnesyl-PPi? | Geranyl-PPi + IPPP |
| What is the first cyclic precursor of cholesterol? | 2,3 epoxide |
| Cholesterol is a precursor of what hormones (9)? | Pregnenolone, Progesterone, DHEA, Androstendione, Testosterone,estradiol, estrone, cortisol, aldosterone |
| How many carbons are in HMG-CoA? | 6C |
| What are the intermediates of Mevalonate to IPPP? | Mevlaonate, Mevalonate 5-Phosphate, Mevalonate 5-PPi, 3-phosphate-5-pyrophosphate mevalonate, IPP |
| How many carbons are in Mevalonate? | 6C |
| How many carbons are in IPPP and DMAPP? | 5C |
| How many carbons is Geranyl-PPi? | 10C |
| How many carbons is Farnesyl-PPi? | 15C |
| How many carbons is Squalene? | 30C |
| What forms acetoacetyl CoA? | 2 Acetyl CoA |
| How man carbons are in acetoacetyl CoA? | 4C |
| What enzyme converts squalene to 2,3 epoxide? Where in the cell? | mono-oxygenase, smooth ER |
| What enzyme converts Squalene epoxide to Lanosterol | Oxidosqualene:Lanosterol Cyclase |
| What does oxidosqualene:lanosterol cyclase do? | moves methly groups; C14 to C13 and C8 to C14 |
| How many carbons is Lanosterol? | 30C |
| What three things are involved in the conversion of Lanosterol to Cholesterol? | 1. oxidation of methly's as CO2 |
| How many carbons is cholesterol? | 27C |
| What enzyme catalyzes the formation of HMG-CoA? | HMG-CoA synthase |
| What enzyme catalyzes HMG-CoA to Mevalonate? | HMG-CoA reductase |
| What enzyme catalyzes the formation of 5-phosphomevalonate | mevalonate kinase |
| What enzyme catalyzes the formation of 5-PPi mevalonate? | phophomevalonate kinase |
| What enzyme catalyzes the formation of 3-phophate 5-PPi mevalonate? | diphosphomevalonate kinase |
| What enzyme catalyzes the formation of IPPP? | diphosphomevalonate decarboxylase |
| What enzyme catalyzes the formation of geranyl-PPi? | cis-prenyl transferase |
| What enzyme catalyzes the formation of farnesyl-PPi? | cis-prenyl transferase |
| What enzyme catalyzes the formation of squalene? | squalene synthetase |
| What enzyme regulates cholesterol synthesis? | HMG-CoA reductase |
| What effect does fasting have on HMG-CoA reductase? | decreases activity |
| What effects do insulin and thyroxin have on HMG-CoA reductase? | increase activity |
| What effects do glucagon and glucocorticoids have on HMG-CoA reductase? | decrease activity |
| What is the active form of HMG-CoAR? | dephospohrylated |
| What is the inactive form of HMG-CoAR? | phosphorylated |
| What are the 3 forms of regulation of HMG-CoAR? | transcription of enzyme RNA, proteolysis, phophorylation |
| How does Ch inhibit HMG-CoAR? | indirect inhibition from sterols |
| Farnesyl-PPi is a precursor for what important molecules (3)? | Dolichol phosphate, ubiquinone, GTP-binding proteins |
| What is dolichol phosphate? | anchor upon which oligosaccharides are built before attachment to glycoproteins |
| What is the committed step in cholesterol synthesis? | HMG-CoA reductase |
| What class of drugs block the committed step in Ch synthesis? | statins |
| Why do statins cause muscle pain and weakness? | they block the farnesyl to ubiquinone process used in the ETC |
| Most Ch is transported in what form? | ChE |
| What form of Ch transport is the highest in blood plasma? | LDL |
| What are plasma concentrations in humans? | 5.2 mmol/L or 200 mg/dL |
| How is Ch and ChE absorbed by the gut? | chylomicrons |
| Dietary chylomicrons and biosynthetic VLDLs are depleted by what enzyme? | lipoproetein lipase |
| What receptor in the liver endocytoses chylomicrons? | Hepatic Apo-E receptor |
| What is the function of LDL? | moving cholesterol from the liver to tissues |
| What is the t1/2 of LDL? Why is this important? | 2 days |
| What types of cells have LDL receptors? | fibroblasts, lymphocytes, arterial smooth muscles cells, liver |
| What is the specific LDL receptor? | Apo-B100/E |
| What disease boasts defective Apo-B100/E receptors? | familial hypercholesterolemia |
| The Apo-B100 binding region is located on which terminal end? N or C | N-terminal end extracelluarly |
| The Apo-B100 receptor has what kind of affinity for LDL? Is it saturated? | "high affinity" LDL receptor, it is saturated under normal conditions |
| What are Ch unregulated LDL receptors (2)? | "low affinity" LDL receptor protein |
| What is a scavenger pathway? | present in macrophages, involve SR-A1 and SR-A2 receptors for oxidized LDL |
| What is the role of HDL? | reverse Ch transport; transporting Ch from tissues to the liver |
| What 2 enzymes does HDL donate to maturing chylomicrons and VLDLs? | ApoCII and ApoE |
| What is the role of ApoCII? | it activates lipoprotein lipase |
| What are the two organs that can make HDL? | liver and intestine |
| What are the two ways in which HDL can be synthesized? | ApoA-I binds PL to form pre-beta HDL; budding from ChM/VLDL |
| What enzyme transports Ch from tissues to HDL? | ABC-1 |
| What is ABC-1? | ATP-binding cassette trasporter |
| What enzyme converts Ch to ChE to be stored in HDL? | LCAT |
| What is LCAT? | Lecithin:Cholesterol Acyl Trasnferase |
| What form of HDL transports ChE back to the liver? | HDL2 |
| LCAT is present in HDL that contain what Apo enzyme | Apo A-1 which activates LCAT |
| LCAT transfers the FA from which carbon to Ch? | C-2 |
| What is the most potent form of HDL that can cause efflux of Ch from tissues? | pre-beta-HDL |
| What is the HDL receptor identified as? | SR-B1 |
| What is CETP? | Cholesterol ester transfer protein |
| What is the role of CETP? | facilitates transfer of ChE between lipoproteins |
| What is exchanged in CETP? | ChE from HDL is traded for TAG in VLDL |
| What is ACAT? | Acyl CoA:Cholesterol Acyl transferase |
| What is the role of ACAT? | it catalyzes storage of Ch to ChE |
| What time scale does it take dietary Ch to equilibrate with plasma? | days |
| What time scale does it take dietary Ch to equilibrate with tissue? | weeks |
| Where are primary bile salts formed? | liver |
| Where are secondary bile salts formed? | intestinal bacteria |
| What is the committed step in the synthesis of bile salts? | 7-alpha-hydroxylase |
| What is the main pathway for ridding the body of cholesterol? | bile salts |
Created by:
jlellerm
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