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