4 Cholesterol and Bile Synthesis

1. HMG-CoA reductase is embedded in the ER membrane but catalyzes reactions on the cytosolic side. This orientation most directly facilitates access to:

mitochondrial NADH
cytosolic acetyl-CoA
nuclear DNA
extracellular cholesterol

2. Foam cell formation contributes to atherosclerosis because foam cells:

oxidize fatty acids excessively
accumulate cholesterol esters
increase HDL production
degrade LDL receptors

3. The formation of squalene requires condensation of how many activated isoprene units?

4. The rate-limiting step of bile acid synthesis is catalyzed by:

HMG-CoA reductase
7-α-hydroxylase
LCAT
CETP

5. The conversion of squalene to cholesterol requires which type of reaction?

decarboxylation only
cyclization and reduction
phosphorylation only
transamination

6. Conversion of cholesterol to bile acids occurs only in:

muscle tissue
liver
intestine
pancreas

7. Oxygen is required during cholesterol synthesis primarily for:

ATP formation
epoxide formation
acetyl-CoA production
isoprene activation

8. Bile salts function as detergents because they:

hydrolyze peptide bonds
form micelles that solubilize lipids
degrade triglycerides enzymatically
increase ATP production

9. NADPH is required in cholesterol synthesis because:

cholesterol is highly oxidized
reduction reactions are necessary during ring formation
NADPH activates acetyl-CoA
NADPH hydrolyzes cholesterol esters

10. Conjugation of bile acids improves emulsification primarily because it:

increases molecular weight
lowers pKa, increasing ionization at intestinal pH
decreases polarity
inhibits bacterial metabolism

11. High intracellular cholesterol decreases HMG-CoA reductase levels primarily through:

increased translation of reductase mRNA
decreased transcription mediated by SREBP
increased mitochondrial import of reductase
inhibition of acetyl-CoA formation

12. Secondary bile acids differ from primary bile acids primarily because they:

contain additional hydroxyl groups
lack hydroxyl groups at position 7
are synthesized only in pancreas
contain fewer carbon atoms

13. SREBPs regulate cholesterol synthesis by controlling:

bile salt secretion
transcription of enzymes in cholesterol biosynthesis
fatty acid oxidation in mitochondria
lipoprotein degradation

14. Statins lower serum cholesterol primarily by:

inhibiting bile acid synthesis directly
increasing triglyceride synthesis
inhibiting HMG-CoA reductase, increasing LDL receptor expression
preventing cholesterol absorption in intestine

15. SCAP plays a role in cholesterol regulation primarily by:

degrading cholesterol directly
activating proteases involved in SREBP processing
transporting cholesterol into bile
synthesizing bile acids

16. Insulin increases cholesterol synthesis primarily because it:

stimulates phosphorylation of HMG-CoA reductase
promotes dephosphorylation of HMG-CoA reductase
increases bile acid secretion
decreases acetyl-CoA availability

17. Cholesterol is described as highly nonpolar primarily because it:

lacks oxygen atoms
contains a tetracyclic hydrocarbon ring system
is synthesized only in mitochondria
cannot interact with lipoproteins

18. Glucagon decreases cholesterol synthesis primarily by:

increasing reductase transcription
increasing reductase phosphorylation
activating SREBP cleavage
increasing LDL uptake

19. Humans cannot degrade the tetracyclic ring structure of cholesterol. This implies that cholesterol removal must occur primarily through:

oxidation to CO₂
conversion into glucose
conversion into bile acids
conversion into amino acids

20. Increased cholesterol concentration increases proteolysis of HMG-CoA reductase. This mechanism represents:

feedback inhibition
competitive inhibition
allosteric activation
irreversible enzyme denaturation

21. Approximately what fraction of cholesterol used physiologically is derived from endogenous synthesis?

20%
50%
80%
100%

22. Cholesterol synthesized in the liver is transported to peripheral tissues primarily via:

HDL only
LDL formed from VLDL metabolism
chylomicrons only
albumin-bound cholesterol

23. Dietary cholesterol is absorbed in the small intestine primarily via:

simple diffusion only
mixed micelles containing lipids
active transport with ATP hydrolysis
chylomicron receptors

24. HDL contributes to cardiovascular protection primarily by:

synthesizing cholesterol
transporting cholesterol from tissues to liver
converting cholesterol directly into bile acids
inhibiting LDL receptor expression

25. Cholesterol’s extreme hydrophobicity contributes to its biological usefulness but also presents challenges because it:

cannot be stored in membranes
must be transported in specialized particles
spontaneously degrades in cytosol
inhibits enzyme activity directly

26. LCAT contributes to reverse cholesterol transport by:

converting cholesterol to bile acids
esterifying cholesterol within HDL
hydrolyzing triglycerides in VLDL
converting LDL to HDL

27. Cholesterol synthesis occurs primarily in which cellular location?

mitochondrial matrix
cytosol and cytoplasmic face of ER
nucleus
lysosome

28. CETP facilitates lipid exchange by transferring:

cholesterol esters to HDL only
triglycerides to HDL only
cholesterol esters from HDL to VLDL
phospholipids to albumin

29. The rate-limiting step of cholesterol synthesis involves conversion of:

acetyl-CoA → citrate
HMG-CoA → mevalonate
squalene → cholesterol
mevalonate → isoprene

30. ABCA1 promotes cholesterol homeostasis primarily by:

synthesizing bile acids
transporting cholesterol out of cells
converting cholesterol to triglycerides
degrading cholesterol in lysosomes