Cholesterol and Lipoprotein Metabolism

Question 1

Where is ApoB found?

Answer 1

VLDL, IDL (chylomicron remnants), LDL

-All considered atherogenic

Question 2

Where is ApoA-1 and 2 found?

Answer 2

HDL

Question 3

What is ApoE and where is it found?

Answer 3

Expressed on chylomicron remnant, IDL, HDL. Binds to LDLR for uptake into liver

Question 4

What is ApoC-II and where is it found?

Answer 4

Found on chylomicrons and VLDL. Required cofactor for LPL (needed to activate it)

Question 5

What is LPL?

Answer 5

Hydrolyzes TGs and frees fatty acids to be taken up by the tissue as fuel. FAs in chylomicron are depleted and eventually you get a chylomicron remnant. In other words, LPL is req for the breakdown of chylomicrons

Question 6

ApoB-48

Answer 6

On chylomicrons

Question 7

Chylomicron vs VLDL

Answer 7

Chylomicron is from the gut (i.e. food source) VLDL is from the liver (i.e. fatty acids in body were broken down, went to liver, packaged in VLDL and transported into systemic circulation). VLDL then drops off FAs at key tissues. Eventually they become IDL (remnants)

Question 8

IDL

Answer 8

VLDL remnants that either allow their ApoE to bind to LDLR and can be taken up to liver for breakdown or that lose their ApoE via conversion to LDLs by hepatic lipase.

Question 9

LDL

Answer 9

LDL is IDL without TG or ApoE. It does, however, still have ApoB-100, allowing it to interact with the LDLR receptor. However, since they don’t have ApoE also, they are less likely to interact than IDL or other particles

Question 10

Where is ApoB-100 expressed?

Answer 10

VLDL, IDL, LDL

Question 11

What lipoprotein is affected in familial chylomicronemia syndrome (FCS)?

Answer 11

Chylomicron

Question 12

What is the etiology of FCS?

Answer 12

Mutation in LPL doesn’t allow it to hydrolyze TGs (i.e. break down chylomicrons in the blood) OR mutations in ApoC-2 doesn’t allow LPL to activate

Question 13

What is your TG level in FCS?

Answer 13

Very elevated

Question 14

What are the physical exam findings in FCS?

Answer 14

Eruptive xanthomas (specific to hyperchylomicronemia)

Question 15

Clinical consequences of FCS

Answer 15

Pancreatitis

Question 16

What lipoprotein is affected with familial hypercholesterolemia (FH)?

Answer 16

LDL

Question 17

What is the etiology of FH?

Answer 17

LDL receptor mutation so that LDL, IDL and CM cannot be taken up by liver
–common disorder

Question 18

What is your TG level in FH?

Answer 18

Normal

Question 19

Physical exam findings with FH?

Answer 19

Heterozygous: tendon xanthoma (specific), corneal arcus and xanthelasma (common but not specific)

Homozygous: Cutaneous xanthomas

Question 20

Clinical consequences of FH

Answer 20

• CHD

- Homozygotes have early onset heart disease

Question 21

What lipoprotein is affected with familial combined hyperlipidemia (FCHL)?

Answer 21

VLDL and LDL

Question 22

What is the etiology of FCHL?

Answer 22

Unknown but there is an overproduction of VLDL by the liver with unknown cause (i.e. no insulin resistance etc)

Question 23

What are the physical exam findings with FCHL?

Answer 23

None

Question 24

What is the clinical consequences of FCHL?

Answer 24

CHD

Question 25

What lipoprotein is affected with familial Dysbetalipoproteinemia (FD)

Answer 25

Remnants (IDL and chylomicron)

Question 26

Etiology of FD?

Answer 26

mutations in ApoE-II so remnants can’t bind LDLR

Question 27

TG level in FD?

Answer 27

Elevated

Question 28

Physical findings in FD?

Answer 28

Eruptive palmar tubero xanthomas

Question 29

Clinical consequences of FD?

Answer 29

CHD, peripheral arterial disease

Question 30

What lipoprotein is affected with familial hypertriglyceridemia (FHTG)

Answer 30

VLDL

Question 31

Etiology of FHTG?

Answer 31

Unknown

Question 32

TG level in FHTG?

Answer 32

Elevated

Question 33

Clinical consequence of FHTG?

Answer 33

None really, but if these people are obese or drink a lot etc, more likely to have problems

Question 34

What lipoprotein is affected with SEVERE FHTG?

Answer 34

Chylomicrons and VLDL

Question 35

TG level in severe FHTG?

Answer 35

Very elevated

Question 36

Etiology of severe FHTG

Answer 36

Unknown (progression?)

Question 37

Physical findings in severe FHTG

Answer 37

Eruptive

Question 38

Clinical significance of severe FHTC?

Answer 38

Pancreatitis (linked to large elevation in TGs)

Question 39

Apo(a)

Answer 39

Lipoprotein with an apo(a) that hangs off of Apo-B and is a major genetic risk factor for CHD and is homologous to plasminogen

Question 40

Epidemiologically, levels of HDL have what relationship to CHD?

Answer 40

Inverse

Question 41

Where is HDL made?

Answer 41

HDL comes from macrophages which have lots of free cholesterol. ABCA1 allows free cholesterol to add to nascent HDL.

Question 42

LCAT

Answer 42

Sits on nascent HDL and esterifies cholesterol allowing HDL to become mature and return to the liver

Question 43

ApoA-1 Mutations

Answer 43

Mutation in apoA1 gene (role in biogenesis and formation of HDL) causes nascent HDL to be nonfunctional and be catabolized rapidly

-leads to rapid removal of nascent HDL particle before mature assembly

Question 44

Clinical outcomes of apoA1 mutations

Answer 44

Low HDL, no increased risk for CVD

Question 45

Tangier Disease

Answer 45

ABCA1 mutation causing faulty transport of free cholesterol from macrophages into HDL. Have a buildup of cholesterol in macrophages and low HDL

Question 46

Clinical outcomes of tangier disease

Answer 46

Low HDL, no inc risk for CVD

Question 47

LCAT deficiency

Answer 47

Mutation in LCAT gene means that cholesterol cannot be deposited into the center of HDL causing a buildup of free cholesterol

Question 48

Physical findings of LCAT deficiency

Answer 48

Cholesterol gets deposited in cornea

Question 49

Clinical consequences of LCAT def

Answer 49

Low HDL but do not have higher risk for CVD