| 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 |
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