Cholesterol and HDL metabolism Flashcards

1
Q

What is HDL

A

Smallest but most dense lipoprotein
Good cholesterol
carries cholesterol from tissue back to liver
excreted in bile
low levels increase risk for heart disease

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2
Q

What is reverse cholesterol transport

A

Pathway that uses HDL to carry excess cholesterol from non-hepatic cells back to the liver for excretion into bile

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3
Q

Why is HDL referred to as good

A

HDL is referred to as “good” cholesterol because it is cholesterol
that is being removed from your body and will not contribute to
atherosclerosis

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4
Q

Main organ of cholesterol synthesis and excretion

A

liver

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5
Q

How much cholesterol is excreted per day

A

1g

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6
Q

Step 1 of reverse cholesterol transport

A

Formation of nascent HDL

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7
Q

Step 2 of reverse cholesterol transport

A

HDL maturation

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8
Q

Describe formation of nascent HDL

A

Derived from liver products
Consists of ApoA1, FR and phospholipid
ABCA1 transfers FC/PC from liver cells to apoA1 for nascent HDL formation
apoA1- forms a belt around the lipid
Nascent HDL functions as a cholesterol acceptor

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9
Q

Describe HDL maturation

A

Maturation of the nascent discoidal HDL to spherical HDL through the actions of LCAT

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10
Q

Describe the LCAT reaction

A

LCAT reaction occurs at the surface of nascent HDL
LCAT binds to apoA1 to become activated
LCAT releases the FA from PC to generate CE
LCAT increases the CE content of HDL

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11
Q

t/F HDL contains a lot of other proteins and lipids

A

true

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12
Q

Step 3 of reverse cholesterol transport

A

Delivery of cholesterol from tissues on HDL to the liver

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13
Q

describe the delivery of cholesterol from tissues on HDL to the liver

A

Uptake of HDL-cholesterol by the liver occurs by scavenger receptor

Uptake of HDL-cholesterol by the liver
produces lipid-poor HDL which recirculate and can pick up more cholesterol from non-liver tissues

Cholesterol from HDL is preferentially excreted into bile into the small
intestine and eliminated in feces

Scavenger receptors have a greater affinity for mature HDL

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14
Q

How is LCAT activated

A

apoA1 binds it

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15
Q

How does removing cholesterol from tissues via HDL prevent or reverse atherosclerosis

A

Increasing cholesterol efflux from macrophages in the artery wall will minimize reduce foam cell formation
Reverse plaque formation (plaque regression)

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16
Q

How do you increase HDL levels

A

Increase HDL levels by:
increasing ApoA1 levels
Increasing LCAT levels
Niacin

17
Q

What is niacin

A

Vitamin B3 supplement
Precursor for NAD and NADP
Decreases lipid levels
if taken at high doses causes liver damage
Increases HDL cholesterol and apoA1
moderately effective

18
Q

How do you increase cholesterol efflux

A

Provide more cholesterol acceptors –> more nascent discoidal HDL

19
Q

How do you increase the number of nascent discoidal HDL

A

Infuse and HDL mimetic

20
Q

what is an HDL mimetic

A

artificial nascent HDL that doesn’t have free cholesterol

21
Q

What is CER-001? Can it reverse atherosclerosis

A

drug that stimulates reverse-cholesterol transport

Increased HDL in humans

No plaque regression

22
Q

3 diseases of HDL metabolism? What is the common effect

A

apoA1
LCAT deficiency
ABCA1-deficiency
Formation of mature HDL is impaired

23
Q

What is familial apoAI deficiency? What is severity dependent on? Diagnosis? treatment?

A

Mutation in APOA1 gene
less than 1 in 1 million

Depend on the mutation:
1. Mutations that reduce apoA1 levels –> low HDL, milder cardiovascular symptoms
2. Complete apoAI deficiency –> impaired reverse-cholesterol transport, very low HDL, high risk of early-onset atherosclerosis

Diagnosis: xanthomas, premature atherosclerosis, low HDL

Treatment: no cure, Statins can lower blood cholesterol

24
Q

What is Familial LCAT deficiency? Symptoms? Treatment?

A

Very rare
Single nucleotide mutation resulting in no LCAT activity in plasma
Can’t convert nascent HDL to mature HDL
decreased HDL

Corneal opacity and kidney damage

some develop atherosclerosis

Enzyme replacement therapy: Pure LCAT infusion was safe and well tolerated, however it is not sustained long-term and would need multiple injections