BC 37 38 Lipo Meta and Dyslipo

Question 1

Apo B48 as structural protein

Answer 1

CM and CM remnants

Question 2

Apo B100 as structural protien (and LDL R Ligand)

Answer 2

VLDL (transport liver-syntesized TAG)

IDL LDL

Question 3

Apo A-I#

Answer 3

HDL

Question 4

what activates lipoprotein lipase

Answer 4

Apo CII

Question 5

what is the ligant do Apo E receptor

Answer 5

Apo E

Question 6

Lipoprotien size comparison and density

Answer 6

CM>VLDL>LDL>HDL

CM<HDL

variable

Question 7

Apo CII as activator of LPL enzyme

Answer 7

CM
VLDL
HDL

Question 8

Apo E as ligand to Apo E receptor

Answer 8

CM, CM rem, VLDL, IDL, HDL

NO LDL

Question 9

Abetalipoproteinemia (CM Retention Disease)

Answer 9

Loss of Function Mutation of MTP gene

loss of MTP means TAGS are not trasfered to the nascent CM and the nascent VLDL
-nacent CM inenterocytes and nascent VLDL in hepatocytes CANNOT be assembled

Cm VLDL and LDL are almost absent from plasma - hypolipidemia (lipid droplet acuumulation in enterocytes) (Wheelchair, weakness/deform)

Dietary fat accumulation in enterocytes

failure to thrive

neurological defects due to malabsorbtion of fat soluble vitamins

Therapy: low fat, calorie rich diet with high dose vitamin supplement

Question 10

Familial Chylomicroanemia (Type I hyperlipidemia)

Answer 10

deficiency in LDL or of ApoCII

TAG in the CM cannot be hydrolized. CM remains to be TAG rich

Elevated fasting CM (high TAG)

• serum appears milky and turbid, cent-> creamy top layer
• cholesterol levels appear normal

Erruptive Xanthomata after high fat meal (TAG righ CM under skin)
-pancreatitis with no rick in Cardio disease

Threapy: reduce CM prod, consume med and short chain TAGs instead of long chain ones plus fat soluble vitamin supplementation

Question 11

Familial Combined hyperlipidemia Type IIb

Answer 11

common: 1/200

Overproduction of ApoB enzyme
2o: metabolic syndrome, obesity, insulin res, hypertension

-Excessive production of VLDLs
(serum appears cloudy/dirty

Elevated VLDL (high TAG) and elevated LDL (high CE)

few clinical manifestations, however still problematic

HIGH risk of premature cardiovascular disease
Threapy: correct 2o cause of lifestyle and diet.

COMBO drug therapyL reduce hypertriacylglyceridemia (niacin) and hypercholesteremia (statins and resins)

Question 12

Familial dysbetalipoprotienemia (FDBL) Type III

Answer 12

polymorphism of apo E gene
-ApoE-2 varient binds poorly to Apo E receptor.
2o high fat diet, diabetes, obesity, hypothyroidism, estrogen deficiency and alcohol use

need prim and secondary to manifest

in ApoE2/ApoE2 homozygous decreased clearing of IDL and CM remnants are observed

lipid profile: elevated IDL and CM remnants

Serum TAGs and chol are both elevated

Tuberoeruptive (yellow legions usuallyh on elbows/knees), orange yellow discolor of palms) and or striate palmar xanthomata
-premature coronary and peripheral vascular diseases

Therapy: correct the 2o lifestyple and diet
-combo drug therapy to reduce hypertriacylglyceridemia (niacin or fibrates) and hypercholeseremia

Question 13

LDL’s in atherosclerosis

Answer 13

LDL long lifetime in blood (1.5-2 days) compares to few hours for other lipoprotiens

LDL is small enough to penetrate from Blood vessel lumen into subendothelial space (LDL oxidised here (oxLDL)

THREE PHASES

1. chronic endothelial arrangement and macrophage recruitment (inflammation of endothelial cells by modifying vessel walls
   - toxins, free rads, and glycation due to hyperglycemia promote oxidation of LDL. LEvel of oxLDL proportional to LDL, oxLDL increases case of hypercholesteremia
   - enflamed endothelial cells recruit blood monocytes, mature to macrophages, become overactive and release ROS (reactive oxygen species (oxidize LDL in intima
2. Macrophages phagocytose oxLDL, particles in the intima via scavenger receptors that are in contrast to LDL receptors NOT down regulated by high intracellylar chol concentrations.
   - chol cannot be degraded, machrophages accumulate oxLDL chol and turn into FOAM CELLS
   - -> FATTY streaks!
3. Plaque formation: activated macrophages secrete proinflammatory cytokins which stim SMC to micrate INTO subendothelial space. proliferate and synthesize fibrous material ie collagen. The restuls is formation of a fibrous cap underneat endothelium narrowing vessesls

INCREASE total serum LDL increase CVD risk

Question 14

HDL function

Answer 14

HDL comprises of heterogenous family of lipoprotiens with metabolism not fully understood.

1. reservoir of apoliporportiens (apo CII and Apo E)
   - apo CII transferred to nascent VLDL and nascent CM, activator of LPL
   - apo E is required for hepatic Apo E receptor mediated endocytosis of IDLs and CM remnants

-Crucial role in chol transport

HDL only way to get chol out of cells

Question 15

CETP

Answer 15

cholesterol ester tranfer protien
-PL and TAGs from VLDL to HDL to VLDL and vice versa

-what is the point? and why from HDL to VLDL

Question 16

so if we have higher CETP activity, which lipoprotien is elevated?

Answer 16

LDL Bad, and risk for atherosclerisis increase

Question 17

Tangier Disease

Alpha-lipoprotien Deficiency

Answer 17

Defect in ABCA1
-ABCA1 plays key role in first stem of reverse cholesterol transport - method for efflux of free chol from peripheral cells is transferred to CE poor HDL3

Defective ABCA1 reduces chol transport out of periperal cells leads to accumulation of CE in body tissues

• prevents maturation of HDL (from HDL 3), nascent HDL 3 degraded
• APo E and Apo C II transfer from HDL to CM and VLDLare also prevented

Low HDL and low LDL, elevated fasting CM and VLDL
-hypertriacylclycerolemia

LARGE TONSILS, premature myoI, clouding of cornea, periperal neuropathy

Question 18

Drugs for hypertriacylglycerolemia and to increase HDL

Answer 18

Niacin: inhibits lipolysis -> a decrease in VLDL and LDL production
-decreases ApoAI breakdown extending HDL’s t1/2

Fibrate: activates LPL, increase in VLDL clearance
fibrates decrease nascent VLDL secretion

inctreases Apo A-I gene expression. increasing HDL production