Test 1: Wk1: 2 Lipoproteins - Valentovic Flashcards
hyperlipidemia
high levels of cholesterol and or triglycerides
Dyslipidemia
abnormal levels of cholesterol and or triglycerides (usually too high) and HDL levels are too low
Elevated Cholesterol associated with
increased atherosclerotic CVD
Elevated triglycerides associated with
pancreatitis
how are cholesterol and triglycerides transported
they are hydrophobic so must be transported by lipoproteins
lipoproteins
Lipoproteins have a hydrophilic outside layer with proteins,
phospholipids and unesterified cholesterol surrounding the
hydrophobic/lipophilic core of triglycerides and cholesterol esters
Lipoproteins transport
Lipoproteins transport fat soluble vitamins, cholesterol and
triglycerides in plasma, lymph as well as liver and peripheral tissues
3 Functions of Lipoproteins
- Involved in absorption and transport of dietary lipids from small
intestine - Transport lipids from the liver to peripheral tissues
- Transport lipids from peripheral tissue to liver and small intestine
5 Major lipoproteins
Chylomicrons
VLDL very low density lipoprotein
IDL intermediate density
LDL low density
HDL high density
Triglyceride mostly carried by — and —
Triglyceride mostly carried by chylomicrons and VLDL
Cholesterol mostly carried in — and —- as cholesterol
—
Cholesterol mostly carried in LDL and HDL as cholesterol
esters
Chylomicron Major Lipids
Triglycerides,
Retinyl esters
Chylomicron Apoprotein
Apo B-48, Apo E, Apo CII
and C III, Apo AI and AII
ApoB-48 only in chylomicron
VLDL Major Lipids
Triglycerides,
vit E
VLDL Apoproteins
Apo B100, Apo E, Apo
CII and Apo CIII
IDL Major Lipids
Triglycerides
Vit E
IDL Apoproteins
ApoB-100
Apo-E
Apo-CII
Apo-CIII
LDL Major Lipids
Cholesterol
Vit E
LDL Apoprotein
Apo B-100
HDL Major Lipids
Cholesterol
HDL Apoprotein
Apo B-100 Apo-E Apo CII Apo CIII Apo-Al Apo AII
Chylomicron formation
Dietary Cholesterol, retinol are esterified, long chain (12 carbon) fatty
acids are incorporated into triglycerides and packaged with Apo B 48,
phospholipids to form chylomicrons
Chylomicrons secreted into — — and enter — —
Chylomicrons secreted into intestinal lymph and enter systemic
circulation
— — on — — of capillaries cleave off FFAs into circulation
Lipoprotein Lipase on endothelial cells of capillaries cleave off FFAs into circulation
Apolipoproteins transferred to —
Apolipoproteins transferred to HDL
Chylomicron must have — to interact with hepatic LDL receptor
Chylomicron must have Apo E to interact with hepatic LDL receptor
— are generated in the liver and are triglyceride rich
VLDL are generated in the liver and are triglyceride rich
Function of VLDL
esterification of LCFAs
VLDL contain what 4 lipoproteins
Apo B-100
Apo-E
Apo-CII
Apo-CIII
VLDL composition
Triglycerides -, Cholesterol -, -Proteins, - Other Fats
Triglycerides 70%, Cholesterol 10%, 10% Proteins, 10% Other Fats
VLDL Metabolism
Lipoprotein lipase on endothelial cells of capillaries (adipose tissue, heart skeletal
muscle) cleave off free fatty acids into the circulation form remnants
IDL are
equal amounts cholesterol and triglycerides
IDL are endocytosed by
the liver
IDL - hepatic lipases hydrolyze TG and apoB-100 transferred to —
IDL - hepatic lipases hydrolyze TG and apoB-100 transferred to HDL
IDL forms
LDL
the majority of cholesterol in the blood stream is
LDL
LDL apoproteins
B100 and ApoE
LDL has a positive correlation with
atherosclerotic CVD
LDL composition
Cholesterol —, Triglycerides —, Proteins —, Other
fats —
Cholesterol 26%, Triglycerides 10%, Proteins 25%, Other
fats 10%
Chylomicrons are generated from
dietary lipids
VLDL is synthesized in
liver
— cleaves FFA from chylomicrons and —
LPL cleaves FFA from chylomicrons and VLDL
VLDL cleaved by — to —
and —
VLDL cleaved by LPL to IDL
and LDL
LDL receptors recognize
LDL receptors recognize
Apo B 100 and Apo E
HDL is generated
in the SI and liver
HDL composition
— Apoprotein, —
phospholipid and —
lipids
50% Apoprotein, 30%
phospholipid and 20%
lipids
— has a negative risk for CVD
HDL has a negative risk for CVD
Cholesterol not metabolized in ---, must be transported to the --- for excretion in ---
Cholesterol not metabolized in peripheral tissue, must be transported to the liver for excretion in bile
--- and other cells provide free cholesterol that is esterified by LCAT Form mature
Macrophages and other cells provide free cholesterol that is esterified by LCAT form mature HDL
LCAT
•(lecithin cholesterol
acyltransferase)
Reverse Cholesterol Transport
higher lipids in
predominantly
peripheral tissue
HDL
— taken up by liver via SR BI
HDL taken up by liver via SR BI
HDL Cholesterol ester can be transferred by — to VLDL and chylomicrons
HDL Cholesterol ester can be transferred by cholesteryl
ester transfer protein (CETP) to VLDL and chylomicrons
Dyslipidemias
Excess levels of cholesterol and triglycerides due to
multiple causes
Primary Dyslipidemias
dietary and genetic
Secondary Dyslipidemias
Disease and Drugs
High — decreases risk of cardiovascular disease
High HDL decreases risk of cardiovascular disease
— positive correlation with Coronary Heart Disease
LDL C positive correlation with Coronary Heart Disease
first line of therapy to reduce plasma cholesterol and triglycerides
diet
High cholesterol therapy
Decrease total daily fat intake
Decrease Saturated fat and cholesterol
High triglycerides therapy
May be due to high carbohydrate intake
Reduce carbohydrates and alcohol
Increase exercise will help reduce cholesterol and triglycerides by increasing —
Increase exercise will help reduce cholesterol and triglycerides by increasing HDL
Familial hyperchylomicronemia Fredrickson Type
I
Familial hyperchylomicronemia
Fasting plasma turbid, creamy top layer due to
chylomicrons
Familial hyperchylomicronemia deficiencies
LPL or Apo C II deficiency
Familial hyperchylomicronemia TG
TG >1000 mg/dl
Familial hyperchylomicronemia Tx
dietary fat restriction
Lipoprotein lipase, GPIHBP1 and Apo
CII deficiency elevated
chylomicrons and VLDL
Lipoprotein lipase needed to hydrolyze — to —
Lipoprotein lipase needed to hydrolyze TG to Free fatty
acids
GPIHBP1 transports —- to the apical surface
of the endothelial cells
GPIHBP1 transports lipoprotein lipase to the apical surface
of the endothelial cells
Apo CII activates lipoprotein lipase on —
Apo CII activates lipoprotein lipase on capillaries
Familial
dysbetalipoproteinemia (Apo E2) Fredrickson Type
III
Familial
dysbetalipoproteinemia (Apo E2) high — and —
cholesterol and TG
Familial
dysbetalipoproteinemia (Apo E2) inability to clear
VLDL and LDL
Familial
dysbetalipoproteinemia (Apo E2)
Abnormal apo E called Apo E2 does not bind as efficiently
to — receptor
LDL
Familial hypercholesterolemia (LDL receptor) Fredrickson Type
II
Familial hypercholesterolemia (LDL receptor) LOF mutation for
LDL receptor resulting in diminished LDL activity
Familial hypercholesterolemia (LDL receptor) Excess — and —
Excess LDL, cholesterol
Familial hypercholesterolemia (LDL receptor) high risk for
CHD
Familial hypercholesterolemia (LDL receptor) other sx
corneal arcus and tendon xanthomas
Familial hypercholesterolemia (LDL receptor) autosomal —
dominant
Familial Hypercholesterolemia incidernce
1/250
Familial Hypercholesterolemia high
cholesterol
Familial Hypercholesterolemia variants in —, —, —
LDL receptor
ApoB100
PCSK9
Familial Hypercholesterolemia defective ApoB 100 results in
defects in receptor binding domain needed to interact with LDL receptor
Autosomal dominant hypercholesterolemia
Autosomal dominant hypercholesterolemia type 3 PCSK9
Gain of function mutation in PCSK9
PCSK9 synthesized in ER of —,
- –, — and other
- –
PCSK9 synthesized in ER of liver,
kidney, small intestine and other
tissues
PCSK9 in blood binds to –
receptor and is endocytosed
with —
PCSK9 in blood binds to LDL
receptor and is endocytosed
with LDL
PCSK9 present LDL receptor not
—, less efficient clearance
of —
PCSK9 present LDL receptor not
recycled, less efficient clearance
of LDL C
Familial combined
hyperlipidema type of disorder
polygenic
Familial combined
hyperlipidema high —, and —; high —, and —
VLDL and LDL
TGs and Cholesterol
Familial combined
hyperlipidema
high levels of — relative to plasma —
high levels of apo B-100 relative to plasma LDL-C
Familial combined
hyperlipidema small dense particles of
LDL
4 results of Excessive VLDL secretion
High VLDL, high TG
Low HDL
Elevated Apo B 100
LDL C may be increased
5 Secondary Causes of Excess VLDL
Alcohol abuse
High Carbohydrate diet
Insulin resistance
Obesity
Renal impairment
LIPIDS ELEVATED SECONDARY TO
DISEASE Cholesterol
Biliary disease Renal disease Hypothyroidism Diabetes mellitus Cushing’s syndrome
LIPIDS ELEVATED SECONDARY TO
DISEASE Triglycerides
Alcoholism Renal disease Diabetes mellitus Obesity Cushing’s syndrome (high VLDL
exogenous pathway
transports dietary lipids to the periphery and the liver
endogenous pathway
transports hepatic lipids to the periphery