Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
27 Cards in this Set
- Front
- Back
|
1. What is the structure of cholesterol?
What type of molecule is it? Why is cholesterol associated w/ vascular disease? |
Tetracyclic fused ring
Very nonpolar -insoluble in water (esp when esterified) No known enzymes in human can degrade it and its high relative nonpolarity |
|
|
2. Where do all the carbons in cholesterol come from?
What is cholesterol synthesized from? What are the major sites of cholesterol synthesis? |
Acetate
Acetyl CoA Liver and intestinal epithelial cells |
|
|
3. What happens in phase I of cholesterol synthesis?
|
1. Acetyl CoA undergoes 2 condensation reactions to form HMG-CoA
*enzymes in cytosol catalyze 2. HMG-CoA is converted to mevalonate **HMG-CoA reductase is enzyme (cholesterol decreases its activity) |
|
|
4. Why is the conversion of HMG-CoA to mevalonate important?
What is the cofactor in this reaction? |
It is the rate limiting step and regulated step in cholesterol synthesis
Its activity controls the amount of cholesterol produced by a cell NADPH (reducing agent) |
|
|
5. What happens in phase II of cholesterol synthesis?
|
1. Mevalone --> 5 C isoprene unit
2. Phosphorylated and condensed to form squalene (30 C) |
|
|
6. What happens in phase III of cholesterol synthesis?
|
1. Squalene cyclizes so have rings of steroid nucleus
2. Modifications to form cholesterol |
|
|
7. What happens to dietary cholesterol?
What happens endogenously synthesized cholesterol? |
Incorporated into chylomicrons
-secreted from lymph to blood to deliver cholesterol to other tissues Transported in the blood in VLDL and LDL (very low and low density lipoproteins) |
|
|
8. Where is the major site of cholesterol synthesis?
Why is HDL good cholesterol? Why is LDL bad cholesterol? |
Liver
Picks up cholesterol and takes it back to the liver and to endocrine glands for steroid hormone synthesis Takes cholesterol to peripheral tissues |
|
|
9. How is cholesterol synthesis controlled?
Why is the rate of cholesterol synthesis higher in the liver than the other tissues? |
Feedback regulation
-cholesterol represses transcription of HMG-CoA reductase gene Cholesterol serves as a precursor for bile salts -synthesis of HMG-CoA reductase is also repressed by bile salts |
|
|
10. How does insulin and glucagon affect HMG-CoA reductase?
|
High insulin/low glucagon (fed)
-dephosphorylate -active Low insulin/high glucagon (fasting) -phosphorylate -inactive |
|
|
11. Besides regulating de novo synthesis of cholesterol from acetate how does the concentration of cholesterol regulate the amount of cholesterol entering the cell?
|
Determines the amount of synthesis of LDL receptors of the plasma membrane
When cholesterol is high in the cell, the synthesis of LDL receptors are reduced |
|
|
12. What are the commonly used cholesterol lowering drugs?
How do they lower cholesterol? |
Statins
Have side chain similar to HMG-CoA so they block active site of HMG-CoA reductase Competitive inhibition |
|
|
13. How do statins affect LDL receptors?
|
They cause a decrease in intracellular free cholesterol which results in an increase in LDL receptors (up regulation of LDL receptors)
This leads to increased cholesterol uptake and reduced serum cholesterol **Lower cholesterol level in blood is final target |
|
|
14. How do cholesterol esters compare to regular cholesterol?
What are the enzymes that esterifies cholesterol? What enzyme hyrolyses cholesterol esters? |
More hydrophobic
1. LCAT (lecithin:cholesterol acyltransferase) 2. ACAT (acteyl:cholesterol acyltransferase) Cholesterol ester hydrolase (CEH) |
|
|
15. Where is LCAT located?
Why type of cholesterol does LCAT esterify? Where is ACAT located? |
In the blood
Cholesterol associated w/ HDL In cells -particularly those that store cholesterol for synthesis of steroid hormones |
|
|
16. What does cholesterol do in cell membranes?
What do the effects of cholesterol on membrane structure and function depend upon? What is cholesterol a precursor to? |
Stabilizes components b/c it reduces membrane solute permeability and increases membrane rigidity
Its concentration in the membrane Bile salts (liver) and steroid hormones (endocrine glands) |
|
|
17. What purpose do cholesterol and cholesterol esters in lipoproteins serve?
What four diseases can inappropriate amounts of cholesterol in the body lead to? |
Maintain cholesterol homeostasis
1. Atherosclerosis 2. Diabetes 3. Alzheimer's 4. Strokes |
|
|
18. Why can bile salt production be helpful to the body?
What is the rate limiting step of bile salt synthesis? Where does this reaction occur? |
It's a good way to get rid of cholesterol
Cholesterol --> 7 α hydroxycholesterol ONLY in the LIVER -this is why it is important to transport cholesterol from peripheral tissues to the liver (achieved by HDL) |
|
|
19. What is the enzyme that catalyzes the rate-limiting step?
What happens in this reaction? How is this enzyme regulated? |
7 α-hydroxylase
Add OH group to the C7 position Feedback inhibition -bile salts inhibit the enzyme |
|
|
20. Where are the primary bile acids formed?
Where are bile salts stored? Where are bile salts modified? |
Liver
Gallbladder Intestine |
|
|
21. What creates secondary bile acids?
|
Bacteria
-deconjugate -dehydroxylate |
|
|
22. What are the bile acids made directly from cholesterol?
(two) In healthy individuals, how are these two unconjugated bile acids and why? Which form of bile salt is active in the enterohepatic system? |
1. Cholic acid
2. Chenocholic acid Conjugated (either to glycine or taurine) Conjugation lowers the pK of the bile acid, making them better detergents Only the conjugated salt forms |
|
|
23. Why are the unconjugated bile salts non-functional?
What are primary bile salts? |
Not sufficiently acidic and are mostly nonionized at the pH of the intestine
Conjugated bile salts made directly from cholesterol by human livers |
|
|
24. What can bacterial enzymes in the intestine do to bile salts?
|
Deconjugate (remove) glyco- and tauro- bile salts to free bile salts
Also can dehydroxylate the OH at the C7 position **convert primary bile salts to secondary bile salts -return them to liver |
|
|
25. What are the two secondary bile salts?
What happens to most of the lithocholic acid and why? |
1. Glycodeoxycholate
2. Taurodeoxycholate Excreted in feces b/c this bile salt is too nonpolar to be reabsorbed and taken back to the liver |
|
|
26. What is the enterhepatic system?
What are the components? |
Metabolism related to cholesterol or else cholesterol would accumulate
1. Liver cholesterol --> bile salts 2. Gallbladder 3. Intestine -pool of bile salts -bacteria deconjugate 4. Bile salts reabsorbed and returned to liver for recycling |
|
|
27. What percent of bile salts are reabsorbed by the liver?
What percent of bile salts are secreted in feces? |
95%
5% (due to modifications by bacteria - no longer have right polarity to be reabsorbed by liver) |
