Cholesterol and Lipoproteins Flashcards
LDL-R; mechanism
Receptor-mediated endocytosis; receptor recycled and apolipoprotein endosome fuses with lysosome
Metabolic syndrome symptoms
insulin resistance, hypertension, thrombosis, TAG:HDL ratio >4
Plants and sterols
Can’t synthesize cholesterol; only stigmasterol, ergosterol
Atherogenic lipoproteins
ApoB - VLDL, LDL-C/P, Chylomicrons, IDL
Apolipoproteins and associated apoprotein
ApoB-48 - chylomicrons; synthesized in intestines ApoB-100 - synthesized in liver -VLDLs - along with other apoproteins -IDLs -LDLs ApoA-I and ApoA-II - HDL
Type IIa
Familial Hypercholesteronemia Lipoprotein - LDL Mutation - AD; LDL-R, apoB, PCSK9 Lipid Effect - TC > 275, LDL > 190
Polycystic kidney disease effects which lipid
Increases LDL
Type IV symptoms
Autosomal dominant Pancreatitis
Cholesterol vs cholesteryl esters
Cholesteryl esters - more non-polar, hydrophobic; found in lipoproteins
Effect of hypothyroidism
Increased LDL, Increased TAGs
Apolipoprotein lipid profile
Chylomicrons - highest TAG:Cholesterol ratio VLDLs - high TAG:Cholesterol ratio HDLs - Lowest TAG:cholesterol ratio
PCSK9; mechanism
Serine protease: Binds to EGF-A region of LDL-R Induces endocytosis of complex Lysosomal degradation
Most Important Ischemic Heart Disease Risk Factor
LDL:HDL ratio Lifestyle
Optimal levels of lipids
TC 40/50 Non-HDL
Type I lipid disorder
Hyperchylomicronemia Lipoprotein - Chylomicron Mutation - LPL or apoC-II/III Lipid Effect - TAGs > 2000
LDL-R; regulation
Thyroxine/estrogen - induce LDL-R expression SREBP/Scap - regulation of LDL-R expression PCSK9 - inhibit LDL-R; stimulate it’s degradation
Apoproteins found in all apolipoproteins
ApoC-II = necessary for lipoprotein lipase activation ApoE = necessary for LDL-R/LRP interaction
Major TAG disorders
Type I, IIb, IV
ACAT; function
Esterification of cholesterol into cholesteryl esters
PCSK9; mutations
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
Type V
Hypertriglyceridemia Lipoprotein - VLDL, chylomicron Mutation - LPL or apoC-III Lipid Effect - TAGs > 1000
LPL Deficiency
Severe hypertriglyceridemia
LDL-R; ligand
ApoE
LDL-R; mutations
AD - hypercholesterolemia; mutation of ligand binding region
ACAT; types
ACAT-1 = sebaceous glands, macrophages, adrenocortical ACAT-2 = liver, intestines
Ranges of Lipids
TC = 200-350 = ASCVD risk LDL >100 = ASCVD risk HDL 1000 = pancreatitis
Type III
Dysbetalipoproteinemia Lipoprotein - VLDL, IDL Mutation - overexpression of ApoE-II Lipid Effect - TC/TAGs = 200-500
Major ASCVD disorders
Type IIa, IIb, III
Lipid panel includes?
TC, TAGs, HDL, LDL (calc), Non-HDL (calc) Can include - apoB, LDL-P
Type I symptoms
Autosomal recessive Pancreatitis, hepatosplenmegaly, xanthomas. No increased ASCVD risk
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
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
Type IV
Hypertriglyceridemia Lipoprotein - VLDL Mutation - LPL or apoC-III Lipid Effect - TAGs = 500-1000
Cholesterol synthesis; important steps
HMG-CoA Synthase -Acetyl-CoA + Acetoacetyl-CoA = HMG-CoA HMG-CoA Reductase -HMG-CoA + 2NADPH = mevalonate *Rate-limiting step
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
Function of LPL
To hydrolyze phospholipids: TAG to DAG to MAG
Location of LPL
Capillary endothelium; near adipose tissue, skeletal muscle, heart muscle, glands, etc.
Factors lowering HDL
o Insulin resistance/metabolic syndrome o Anabolic steroids o Trans-fats o Progestins o Smoking
Type IIa symptoms
Autosomal dominant Heterozygotes = TC = 300 mg/dL Homozygotes = TC = 700 mg/dL Accelerated atherosclerosis (MI before 20), xanthomas, corneal arcus
Lipoprotein w/ longest half-life
LDL
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
Factors increasing HDL
o Aerobic exercise o Alcohol o Estrogens
Metabolic Syndrome Criteria
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Obstructive kidney disease affects which lipid
Increases LDL
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
