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Chol Syn & Met

USCSOM: Cholesterol Synthesis and Metabolism

QuestionAnswer
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