L9 Lipid Metabolism and Dyslipidemia Flashcards
Size of Lipoproteins?
HDL< LDL < IDL< VLDL < Chylomicrons
_______________: Modified atherogenic LDL w/ Apo (a), most atherogenic lipoprotein
Lipoprotein A: Modified atherogenic LDL w/ Apo (a)
most atherogenic lipoprotein
What is an important biomarker for increasded CVD risk?
Apo (a) is an important biomarker and indicator CVD risk
measure someone once if high -> increased CVD risk
What is an important biomarker for increasded CVD risk?
Apo (a) is an important biomarker and indicator CVD risk
measure someone once if high -> increased CVD risk
______________:
Absorb dietary triglycerides, some cholesterol
Transports to peripheral tissues and liver
Chylomicrons (ApoB48, ApoE and Apo C-II)
Absorb dietary triglycerides, some cholesterol
Transport to peripheral tissues and liver
______________:
TG-rich
Transport TG and chol around the body –> LDL as they lose Triglycerides
VLDL (ApoB-100 , ApoE and Apo C-II)
TG-rich
Transport TG and chol around the body.
VLDL –> LDL as they lose Triglycerides
___________:
Carries cholesterol in its core to peripheral tissues
Targetted by Statins
Pathogenesis?
LDL (ApoB-100)
Carries cholesterol in its core to peripheral tissues
Pathogenesis:
HIGHER LDL => Increased risk of CVD
LDL is difficult to be taken up by macrophages → atherotic lesions
Modification of LDL (Primarily through oxidation)
Smoking increases oxidation
Once modified more easily taken up
How do Statins function?
LDL receptor in the liver is key one for lipoprotein metabolism
statins upregulate LDL receptor in liver
=> clears LDL from circulation
____________:
Carries cholesterol from peripheral to liver
excretion in bile or feces
Known as Reverse Cholesterol transport
HDL (ApoA-I, ApoA-II, ApoE, Apo C-II)
Carries cholesterol from peripheral to liver
excretion in bile or feces
Known as Reverse Cholesterol transport
LOWER HDL => Increased risk of CVD
LOWER ________ and HIGHER ________ => Increased risk of CVD
LOWER HDL** and HIGHER **LDL => Increased risk of CVD
Role of cholesterol in the body?
How is it regulated?
Cholesterol is used for steroid hormone synthesis and cell wall synthesis.
Cannot be metabolized, only secreted!!
Increased fiber content of diet –> promotes cholesterol secretion in feces
____________ celaves lipoproteins for circulation during endogenous lipoprotein metabolism
APO C II
(Chylomicrons and VLDL)
_________ potent at driving endogenous cholesterol synthesis
Saturated fats potent at driving endogenous cholesterol synthesis
________ and ________ interact with lipoprotein receptors as part of endogenous lipoprotein metabolism
APO E and APO B interact with lipoprotein receptors as part of endogenous lipoprotein metabolism
Familial Hypercholesterolemia Types?
ApoC-II or LPL defect (Type I): Hyperchylomicronemia
=> excessive accumulation of chylomicrons
LDL receptor defect (Type II)
Very hard to treat (Most LDL treatments target LDL receptor expression)
Treat w/ apheresis to filter out excess LDL every few weeks
ApoE defect (Type III)
ApoB-48 is associated with which Lipoproteins?
Chylomicrons
ApoB-100 is associated with which Lipoproteins?
VLDL
IDL
LDL
ApoA is associated with which Lipoproteins?
HDL
ApoE is associated with which Lipoproteins?
Chylomicrons
vLDL
HDL
ApoC is associated with which Lipoproteins?
Chylomicrons
VLDL
HDL
Endogenous Pathway of Lipoprotein Metabolism
Majority of Cholesterol from this
Exogenous pathway of Lipoprotein Metabolism
Exogenous Pathway: taking in from external source
Food eaten –> triglycerides –> cholesterol
Not much cholesterol eaten, when it is upregulated enzymes that break it down
The blood of a person who consumes large amounts of animal fat would most likely contain which one of the following soon after consumption?
A.Increased levels of LDL and HDL
B.Increased levels of HDL
C.Increased levels of VLDL
D.Increased levels of VLDL and HDL
E.Increased levels of chylomicrons
The blood of a person who consumes large amounts of animal fat would most likely contain which one of the following soon after consumption?
A.Increased levels of LDL and HDL
B.Increased levels of HDL
C.Increased levels of VLDL
D.Increased levels of VLDL and HDL
E.Increased levels of chylomicrons
Hyperchylomicronemia: (__________ or ___________ defect)
=> excessive accumulation of chylomicrons
Hyperchylomicronemia:Type I- (ApoC-II**or**Lipoprotein Lipase (LPL) Defect)
=> excessive accumulation of chylomicrons
Dyslipidemia in Diabetes
Increased:
TG
VLDL
LDL
Apo B
Decreased:
HDL
Apo A I
Clinical Manifestations of Dyslipidemia?
Xanthoma (cholesterol deposits in skin/tendons/joints)
Xanthelasma (yellow plaque on eyelids-excess cholesterol)
Lipemia Retinalis (milky retina -excess Chylomicron/TG)
Atherosclerosis
Primary vs. Secondary Management of CVD Risk
Primary prevention aimed at people who already have developed cardiovascular risk factors, such as high blood pressure or high cholesterol => to prevent progression to CVD
Secondary Prevention preventing heart attack and stroke through drug therapy and counseling for high-risk individuals– those with previous events or known CVD
Strategies to Lower LDL Cholesterol Levels?
Avoid dietary trans fat
Reduce Saturated Fats
Increase Fiber Intake
_____________ blocks reabsorption of both biliary and dietary cholesterol from intestine
Ezetimibe blocks reabsorption of both biliary and dietary cholesterol from intestine
______________ block reabsorption of bile-acids into circulation
Bile-acid sequestrants block reabsorption of bile-acids into circulation
__________ represents ~25% of total cholesterol in intestine
__________ represents ~75% of total cholesterol in intestine
Dietary cholesterol represents ~25% of total cholesterol in intestine
Biliary cholesterol (Liver) represents ~75% of total cholesterol in intestine
Intestinal cholesterols absorbed by _________
=> returned to the liver
=>repackaged with _________
Intestinal cholesterols absorbed by chylomicrons
=> returned to the liver
=>repackaged with apoB-100 => from VLDL
A patient with a hyperlipoproteinemia would be most likely to benefit from a low-carbohydrate diet if the lipoproteins that are elevated in the blood belong to which class of lipoproteins?
A.LDL
B.VLDL
C.Chylomicrons
D.Chylomicrons and VLDL
E.HDL
A patient with a hyperlipoproteinemia would be most likely to benefit from a low-carbohydrate diet if the lipoproteins that are elevated in the blood belong to which class of lipoproteins?
A.LDL
B.VLDL
C.Chylomicrons
D.Chylomicrons and VLDL
E.HDL
Factors influencing HDL Levels?
Factors that increase HDL
–Oral estrogens
–Aerobic exercise
–Alcohol intake
Factors that decrease HDL
–Low-fat, high-carbdiets
–Obesity
–Metabolic Syndrome/Hypertriglyceridemia
–Type II diabetes
–Androgens, some progestins
–Beta-blockers
_________ is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight.
Metformin is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight.
Which one of the following is characteristic of high-density lipoprotein?
A. It carries apolipoproteinE, an activator of lipoprotein lipase
B. It is produced by the action of lipoprotein lipase on VLDL
C. It is digested by muscle lysosomes
D. Its major apolipoproteinis apoB48
E. It is remodelled by cholesterol ester transfer protein
REDUCED ______ ASSOCIATED W/ HYPERTRIGLYCERIDEMIA
REDUCED HDL ASSOCIATED W/ HYPERTRIGLYCERIDEMIA
