Cholesterol and Lipoprotein Metabolism

Question 1

What is the basic structure of lipoprotein?

Answer 1

polar surface coat (phospholipid, free cholesterol) and nonpolar lipid core (cholesterol ester, triglyceride) + apolipoproteins (embedded proteins)

Question 2

Purpose of lipoprotein

Answer 2

transport cholesterol

Question 3

Difference between triglycerides and phospholipids

Answer 3

phospholipids have 2 FA tails + phosphate –> polar

Question 4

Lipoproteins with the largest diameter have the highest/lowest density

Answer 4

lowest –> will float (e.g. chylomicrons and chylomicron remants)

Question 5

Which lipoprotein is it in: ApoB

Answer 5

chylomicrons (48), VLDL, IDL, LDL(100) AKA everything except HDL

Question 6

Which lipoprotein is it in: ApoA1

Answer 6

HDL

Question 7

Which lipoprotein is it in:ApoE

Answer 7

VLDL, HDL

Question 8

Which lipoprotein is it in:ApoCII

Answer 8

chylomicrons, VLDL

Question 9

Exogenous pathway for lipoprotein metabolism

Answer 9

fats come from intestine –> TG in chylomicrons –> lymph (aka bypass liver) –> lipoprotein lipase in tissues consumes TG –> frees FA for tissues + releases chylomicron remant (w/ApoE)–> LDLR on liver for cholesterol recylcing

Question 10

What is a required cofactor for lipoprotein lipase?

Answer 10

ApoCII

Question 11

Endogenous pathway of lipoprotein metabolism

Answer 11

FFA in liver adipose packaged in VLDL (B100) and released to blood –> consumed by LPL –> IDL remnant (intermediate) –> further metabolism to LDL (B100) –> LDLR

Question 12

How does DM2 or insulin resistance contribute to hyperlipidemia?

Answer 12

increased adipose lipolysis –> higher liver production of TG –> overproduction of VLDL

Question 13

Why don’t most diabetics have high ldl?

Answer 13

there is often a secondary breakdown in LPL that leaves everything at the VLDL stage

Question 14

Etiology: Familial chylomicronemia syndrome

Answer 14

mutations in LPL or ApoCII lead to reduced breakdown of chylomicrons and result in chylomicronemia

Question 15

Presentation of FCS

Answer 15

eruptive xanthomas, pancreatitis

Question 16

Etiology: Familial dysbetalipoproteinemia

Answer 16

After breakdown of chylomicron, chylomicron remant takes on ApoE which provides docking with the liver (also involved in VLDL remant/IDL uptake)

–> if you have homozyogous ApoE2 instead of 3 or 4, you get buildup of remants of chylomicrons and VLDL

Question 17

Presentation of FD

Answer 17

xnathomata over elbows, palmar xanthomas, CHD

Question 18

Etiology: Familial hypercholesterolemia

Answer 18

mutations in LDLR prevent docking of LDL and disrupts cholesterol metabolism –> LDL buildup

can be heterozyogous or homozygous (worse)

Question 19

Presentation of FH

Answer 19

corneal arcus, xanthelasma, tendon xanthoma (very specific for FH), CHD, normal TG

*significant cutaneous xanthomas in homozyogous FH

Question 20

What’s the difference between FH and FDB

Answer 20

familial defective apoB-100 involves mutation in apoB in the docking strip for LDLR –> same presentation but different mutation

Question 21

Etiology: Autosomal dominant hypercholesterolemia 3 (ADH3)

Answer 21

increased pcsk9 negatively regulates LDL receptor

Question 22

Gain of function or loss of function in Pcsk9 cause severe hypercholesterolemia

Answer 22

gain of function

Question 23

Etiology: Familial hypertriglyceridemia

Answer 23

VLDL metabolism breaks down

Question 24

Clinical presentation of FHTG

Answer 24

high VLDL and triglycerides –> if type 5 (severe) severe eruptive xanthomas, pancreatitis, CHD

Question 25

What is type 5 FHTG?

Answer 25

it is an advanced form that results in high VLDL AND high chylomicrons

Question 26

Etiology: Familial combined hyperlipidemia FCHL

Answer 26

combined disorder leading to overproduction of VLDL (like in DM2 but have normal LPL) --> high VLDL, high IDL, high LDL

Question 27

Clinical presentation of FCHL

Answer 27

CHD, high V/I/LDLs

Question 28

What is Lp(a)

Answer 28

independent risk factor for CHD, highly genetically determined, unknown function, homologous to plasminogen --> bound to ApoB and hangs off the particle

Question 29

What is the relationship between HDL and CHD?

Answer 29

inverse

Question 30

HDL structure

Answer 30

TG/CE core with phospholipids + ApoA1

Question 31

What is the reverse cholesterol transport pathway

Answer 31

HDL interacts with cells like macrophages and promote cholesterol efflux from cells and transports esterified cholesterol back to liver for excretion in bile

Question 32

Primary genetic causes of low HDL (hypoalphalipoproteinemia)

Answer 32

``` ApoA1 mutation - rapid catabolism Tangier disease (ABCA1) - cholesterol transport from macrophages to HDL broken down LCAT deficiency - breakdown of cholesterol ester formation in HDL molecules ```

Question 33

Is there a causal link between HDL and coronary disease

Answer 33

not clear --> but independent risk factor for CHD risk

Question 34

Clinical finding in LCAT deficiency

Answer 34

cloudy cholesterol buildup on cornea

Question 35

Clinical finding in Tangier disease

Answer 35

large orange tonsils