Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

BMIS 435 > Cholesterol and Atherosclerosis > Flashcards

Cholesterol and Atherosclerosis Flashcards

(63 cards)

Start Studying
1
Q

What is cardiovascular disease

A

Condition that affects the structure or function of the heart

Heart disease is the #1 killer in the USA
2nd leading cause of death in Canada

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is atherosclerosis? What are plaques? What is atherosclerosis caused by?

A

Occurs when your arteries become clogged with plaque, causing them to lose elasticity and become narrower
The hardening of the arteries
Plaques are hard deposits of cholesterol and macrophages
Caused by damage to the inner layers of the arteries (smoking, high blood pressure, high cholesterol)
INCREASED LDL = ATHEROSCLEROSIS
Plaque narrows the arteries and can rupture and block arteries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is atherogenesis? What are the 5 steps?

A

Atherosclerotic plaque formation

  1. Damage to artery wall which causes accumulation of LDL
  2. Inflammatory response which attracts monocytes to damaged site
  3. Monocytes differentiate into macrophages which take up cholesterol
  4. Macrophages become lipid-rich foam cells
  5. Foam cells accumulate to form plaque
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is a macrophage foam cell

A

Cytoplasm filled with a large number of lipid droplets that contain cholesterol ester

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

roles of cholesterol

A

Bile acids
Steroid hormones
Membrane fluidity
cholesterol ester

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the synthesis of primary bile acids? What is the role of bile acids?

A

synthesis occurs in liver, the rate limiting step is when C7 of cholesterol is acted on by 7a-hydroxylase to become 7a hydroxycholesterol
Goes through a series of reactions to create primary bile acids
Bile acids are involved in dietary lipid digestion
acts as emulsifiers and help in cholesterol excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the rate-limiting step of bile acid synthesis

A

Rate-limiting step is cholesterol to 7a-hydroxycholesterol

Catalyzed by 7a-hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the synthesis of conjugate bile acids (bile salts)

A

Primary bile acids are converted to bile salts by the addition of glycine via an amide bond

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where are secondary bile acids produced

A

Produced in the small intestine by gut flora

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the only significant way to eliminate cholesterol

A

Excretion of bile in feces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What percentage of bile acids are recycled

A

98%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the enterohepatic circulation of bile acids

A

We also excrete 1g of cholesterol per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Can pancreatic lipase degrade TG alone? What needs to happen to TG?

A

Pancreatic lipase cannot degrade TG efficiently so bile acids help this process

TG has to be emulsified into mixed micelles by bile acids so they can be acted upon by pancreatic lipase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Role of bile acids

A

Needed for intestinal breakdown of TG

Bile acids are detergents that solubilize dietary fats to facilitate their breakdown and absorption

Stored in gall bladder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Bile salt structure

A

Amphipathic
can interact with water and lipids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What do detergents do? example?

A

Bile salts are detergents

solubilize lipids by forming mixed micelles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are gallstones? Cause? Treatment?

A

Solid particles that collect in gall bladder
formed from bile supersaturated with cholesterol
can block bile duct and lead to infection

Caused by high cholesterol and obesity

Drugs can dissolve gallstones
soundwave can break stones into smaller pieces to be passed
Gall bladder removal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

three things

Importance of bile acids

A

Bile acid excretion in feces is the only significant way cholesterol can be eliminated

Can solubilize cholesterol preventing gallstone formation

Facilitate dietary fat absorption by acting as emulsifying agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Sources of cholesterol

A

Diet and synthesized in body

majority synthesized in the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How many stages is cholesterol synthesized in? Starting material?

A

4 stages
Starts with 3 acetyl CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe stage 1 of cholesterol synthesis

A

HMG CoA –> Mevalonate

Synthesized by HMG-CoA reductase

Rate limiting step of cholesterol biosynthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Stage 2 of cholesterol synthesis

A

Activated isoprene formation

Catalyzed by pyrophospho-mevalonate decarboxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Stage 3 of cholesterol synthesis

A

Condensation of 6 isoprene units to squalene
Takes 6 isoprene units to create squalene
catalyzed by squalene synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Stage 4 of cholesterol synthesis

A

Squalene undergoes cyclization to become lanosterol and then multiple steps to become cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Describe the esterification of cholesterol
cholesterol becomes cholesteryl ester catalyzed by ACAT
26
What is cholesteryl ester
Storage form of cholesterol stored in lipid droplets
27
How is cholesterol balance maintained
cholesterol is synthesized in the liver and there is a balance between synthesis and dietary uptake Diet leads to cholesterol Cholesterol inhibits HMG CoA reductase which is the rate-limiting enzyme of cholesterol synthesis
28
What is the rate limiting enzyme of cholesterol biosynthesis
HMG-CoA reductase
29
Describe the Cholesterol and TG transport between tissues
Liver produces VLDL which goes to capillaries and interacts with LPL Half of VLDL remnants are recycled by the liver The other half is converted to LDL in circulation which can continue to the liver or be converted to HDL So the liver indirectly creates LDL
30
Main job of LDL
Transport cholesterol to tissues
31
Describe the receptor mediated endocytosis of LDL
Highly specific process where molecules are absorbed into a cell through invagination of the plasma membrane Apoprotein wraps around LDL which is recognized by LDL receptor which triggers receptor-mediated endocytosis The receptor/ligand interaction gives specificity
32
What is the only protein on LDL
Apoprotein B-100
33
What is cholesterol synthesis regulated by?
Intracellular cholesterol levels
34
Effects of increased and decreased cholesterol levels (HMG CoA reductase, LDL recptor, Synthesis and uptake, cholesterol ester)
35
How is HMG CoA reductase activity regulated
Regulation is layers Phosphorylation/ dephosphorylation Degradation Transcription levels
36
How does a decrease in intracellular cholesterol lead to increased transcription of HMG CoA reductase
SREBP Transcription factors that activates transcription of the gene for HMG-CoA reductase Increases cholesterol synthesis and uptake
37
What are the integral membrane proteins in the ER
SREBP Scap- SREBP Cleavage Activating Protein Insig- Insulin Induced Gene
38
What are the 4 players of HMG-CoA reductase transcription? What are their roles
SREBP- regulates transcription of HMG-CoA reductase Scap- Cholesterol sensor in ER, binds both SREBP and Insig Insig- Scap binding protein in ER, Retains SREBP/Scap in ER S1P and S2P- proteases in golgi, process SREBP to the active form in the golgi
39
Describe the transcription of HMG CoA reductase process
SREBP, Scap, and Insig are all bound together on the ER to start When cholesterol is high, Scap tells insig to retain the other proteins in the ER If cholesterol is low, Scap has a conformational change to unbind insig in the ER Scap-SREBP get incorporated into a vesicle where it is transported to the golgi S1P clips the the transmembrane proteins which releases Scap S2P cleaves SREBP again which releases it from the golgi SREBP is now mature and chaperon proteins bring it to the nucleus where it binds to the target gene to activate HMG CoA reductase transcription
40
What is hypercholesterolemia
high blood cholesterol which increases the risk for heart disease and stroke Promotes atherosclerosis Risk factors: Heredity, lack of exercise, overweight, high blood pressure, smoking Diagnosis by blood test: High LDL cholesterol >200mg/dl)
41
describe familial hypercholesterolemia? (description, Mutation, effects)
Genetic disease caused by LDL receptor defects caused by genetic mutation Many different mutations have been identified in the LDLR LDL cannot be removed from the circulation resulting in high cholesterol in blood and can result in xanthomas and increased plaque formation
42
Heterozygous FH vs Homozygous FH
Heterozygous (relatively common)- 1/250, hypercholesterolemia and premature CV disease, LDL receptor is partially functional, will have high cholesterol, may have xanthomas or no symptoms Homozygous- No functional LDL receptor, 1/1,000,000, Extremely high LDL-cholesterol, atherosclerosis and xanthomas, CV diseases in children, if untreated can be fatal by 30
43
How can heterozygous FH be treated
Exercise/weight loss Dietary changes (reduce cholesterol) Cholesterol lowering drugs (statins)
44
What are statins? What are their effects?
cholesterol lowering drug HMG-CoA reductase inhibitor Inhibit cholesterol synthesis and increase uptake
45
What are bile acid sequestrants (Resins)
Anion exchange resins prevent reabsorption of bile salts, effects additive when used with statins, may inhibit absorption of fat soluble vitamins
46
How do bile acid sequestrants affect bile acid recycling
increase cholesterol excretion as bile salts
47
How can homozygous FH be treated
LDL-apheresis which is the selective binding of apo B lipoproteins Used every 2 weeks (2-4 hours) and it is $3000/treatment
48
What is PCSK9?
Protease produced by the liver which is secreted into the circulation Protein that regulates plasma cholesterol Directs the LDL receptor for degradation by the lysosome
49
How does PCSK9 function
Binds to LDL-R at the cell surface to promote LDLR degradation and prevents recycling LDLR and PCSK9 complexes are internalized into the cell and undergoes lysosomal degradation
50
What do nonsense mutations in PCSK9 gene do? (inhibiting PCSK9)
hypocholesterolemia Increased LDLR LDLR recycling should be increased Decrease blood cholesterol
51
What is a therapy using PCSK9 to reduce plasma cholesterol
PCSK9 antibody neutralizes PCSK9 resulted in increased LDLR and decreased plasma cholesterol
52
Describe PCSK9 inhibitors
They are antibodies 60% reduction in LDL injection every 2-4 weeks can cause mental confusion 15k/patient per year Safe so far
53
What does lysosomal acid lipase (LAL) do
Hydrolyzes cholesterol ester to cholesterol Moves from ER --> golgi --> lysosome via the mannose 6-phosphate pathway
54
What are NPC1/2
cholesterol transporters in the lysosome
55
What enzymes are used for cholesterol ester synthesis and hydrolysis
ACAT: Cholesterol--> cholesterol synthesis LAL: reverse, hydrolysis
56
Describe intracellular cholesterol processing
LDL is internalized and brought to the lysosome and is converted to cholesterol ester LAL makes it free cholesterol NPC1/2 transport FC to the ER where it is sensed by SCAP and then converted to cholesterol ester and transported to lipid droplets
57
Effects of lysosomal acid lipase deficiency
No CE --> FC Accumulation of cholesterol ester in lysosomes and decreased free cholesterol SREBP is activated due to lack of FC Stimulate cholesterol synthesis Premature atherosclerosis
58
Two types of LAL deficiency
Complete absence --> Wolman disease Residual activity (5-10%) --> CE storage disease
59
How can LAL deficiency be treated
Low fat diet Statins Liver transplant Enzyme replacement therapy
60
What happened when skin cells from LAL patient was grown in medium from fibroblasts from a normal person
Decreased cholesterol ester in lysosomes Cultured cells secrete and take up lysosomal hydrolases
61
Which cells can take up LAL
Cells that have mannose 6-phosphate receptor on cell surface
62
What is Sebalipase
recombinant LAL infusion once a week drug to fix LAL deficiency improves liver function
63
What are the primary bile acids
Chenodeoxycholic acid and cholic acid

BMIS 435 (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions