Cholesterol and Lipoproteins Flashcards

1
Q

LDL-R; mechanism

A

Receptor-mediated endocytosis; receptor recycled and apolipoprotein endosome fuses with lysosome

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

Metabolic syndrome symptoms

A

insulin resistance, hypertension, thrombosis, TAG:HDL ratio >4

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

Plants and sterols

A

Can’t synthesize cholesterol; only stigmasterol, ergosterol

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

Atherogenic lipoproteins

A

ApoB - VLDL, LDL-C/P, Chylomicrons, IDL

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

Apolipoproteins and associated apoprotein

A

ApoB-48 - chylomicrons; synthesized in intestines ApoB-100 - synthesized in liver -VLDLs - along with other apoproteins -IDLs -LDLs ApoA-I and ApoA-II - HDL

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

Type IIa

A

Familial Hypercholesteronemia Lipoprotein - LDL Mutation - AD; LDL-R, apoB, PCSK9 Lipid Effect - TC > 275, LDL > 190

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

Polycystic kidney disease effects which lipid

A

Increases LDL

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

Type IV symptoms

A

Autosomal dominant Pancreatitis

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

Cholesterol vs cholesteryl esters

A

Cholesteryl esters - more non-polar, hydrophobic; found in lipoproteins

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

Effect of hypothyroidism

A

Increased LDL, Increased TAGs

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

Apolipoprotein lipid profile

A

Chylomicrons - highest TAG:Cholesterol ratio VLDLs - high TAG:Cholesterol ratio HDLs - Lowest TAG:cholesterol ratio

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

PCSK9; mechanism

A

Serine protease: Binds to EGF-A region of LDL-R Induces endocytosis of complex Lysosomal degradation

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

Most Important Ischemic Heart Disease Risk Factor

A

LDL:HDL ratio Lifestyle

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

Optimal levels of lipids

A

TC 40/50 Non-HDL

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

Type I lipid disorder

A

Hyperchylomicronemia Lipoprotein - Chylomicron Mutation - LPL or apoC-II/III Lipid Effect - TAGs > 2000

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

LDL-R; regulation

A

Thyroxine/estrogen - induce LDL-R expression SREBP/Scap - regulation of LDL-R expression PCSK9 - inhibit LDL-R; stimulate it’s degradation

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

Apoproteins found in all apolipoproteins

A

ApoC-II = necessary for lipoprotein lipase activation ApoE = necessary for LDL-R/LRP interaction

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

Major TAG disorders

A

Type I, IIb, IV

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

ACAT; function

A

Esterification of cholesterol into cholesteryl esters

15
Q

PCSK9; mutations

A

Overexpression = decreased LDL-R = increased cholesterol levels = Increased CVD risk Underexpression = increased LDL-R = decreased cholesterol levels = decreased CVD risk AD - gain-of-function = increased CVD risk

16
Q

Type V

A

Hypertriglyceridemia Lipoprotein - VLDL, chylomicron Mutation - LPL or apoC-III Lipid Effect - TAGs > 1000

18
Q

LPL Deficiency

A

Severe hypertriglyceridemia

19
Q

LDL-R; ligand

21
Q

LDL-R; mutations

A

AD - hypercholesterolemia; mutation of ligand binding region

22
ACAT; types
ACAT-1 = sebaceous glands, macrophages, adrenocortical ACAT-2 = liver, intestines
23
Ranges of Lipids
TC = 200-350 = ASCVD risk LDL \>100 = ASCVD risk HDL 1000 = pancreatitis
24
Type III
Dysbetalipoproteinemia Lipoprotein - VLDL, IDL Mutation - overexpression of ApoE-II Lipid Effect - TC/TAGs = 200-500
25
Major ASCVD disorders
Type IIa, IIb, III
26
Lipid panel includes?
TC, TAGs, HDL, LDL (calc), Non-HDL (calc) Can include - apoB, LDL-P
27
Type I symptoms
Autosomal recessive Pancreatitis, hepatosplenmegaly, xanthomas. No increased ASCVD risk
29
Regulation of LPL
High glycogen, fats = Induction of LPL for storage of lipids into adipose tissue Fasting = decreased LPL expression; prevents storage of lipids out of plasma
30
Cholesterol is a precursor for what
Gonads -pregnenlone to progesterone to androgens to estrogens Adrenal -progesterone to mineralcorticoids (aldosterone and corticosterone) and glucocorticoids Vitamin D -7-dehydrocholesterol to cholecalciferol (Vitamin D) Liver -7-hydroxycholesterol to bile acid
31
Type IV
Hypertriglyceridemia Lipoprotein - VLDL Mutation - LPL or apoC-III Lipid Effect - TAGs = 500-1000
32
Cholesterol synthesis; important steps
HMG-CoA Synthase -Acetyl-CoA + Acetoacetyl-CoA = HMG-CoA HMG-CoA Reductase -HMG-CoA + 2NADPH = mevalonate \*Rate-limiting step
34
Cofactors of LPL
Heparin - anchors LPL to capillary endothelia IV heparin - used to displace LPL into plasma; for measuring LPL levels ApoC-II - obligatory cofactor
35
Function of LPL
To hydrolyze phospholipids: TAG to DAG to MAG
36
Location of LPL
Capillary endothelium; near adipose tissue, skeletal muscle, heart muscle, glands, etc.
36
Factors lowering HDL
o Insulin resistance/metabolic syndrome o Anabolic steroids o Trans-fats o Progestins o Smoking
37
Type IIa symptoms
Autosomal dominant Heterozygotes = TC = 300 mg/dL Homozygotes = TC = 700 mg/dL Accelerated atherosclerosis (MI before 20), xanthomas, corneal arcus
39
Lipoprotein w/ longest half-life
LDL
40
Type IIb
Familial Compound Hyperlipidemia Lipoprotein - VLDL, LDL Mutation - metabolic syndrome/insulin resistance; ApoB-100 Lipid Effect - TC = 100, TAGs = 200-500, HDL \< 40/50 increased VLDL remnants and LDL-P
41
Factors increasing HDL
o Aerobic exercise o Alcohol o Estrogens
43
Metabolic Syndrome Criteria
add picture
44
Obstructive kidney disease affects which lipid
Increases LDL
45
What is the exogenous pathway of apolipoproteins
Dietary lipids in intestinal lumen (1) intestinal epithelial cell cytoplasm (2) esterification of cholesterol (3) efflux of plant sterols (4) chylomicron formation (5) transport of lipids to liver and tissues (6) chylomicron remnants 1 = NPC1L1 = influx of lipids into epithelial -ezetimibe targets NPC1L1 2 = ACAT-2 3 = ABCG5/8 = efflux of plant sterols out of cell -Mutation = sitosterolemia = xanthomas, increased CVD risk 4 = MTP = apoB-48 synthesized in intestine; MTP transports esters to apoB-48 5 = LDL-R/apoE 6 = processed by liver -apoB-48 degraded -other apoproteins recycled to HDL