Cholesterol Biosynthesis, Transport and Genetics 2 Flashcards
Most foods that are high in cholesterol are also high in what?
saturated fatty acids
Which foods increase cardiovascular disease risk?
foods high in saturated fatty acids aka trans-fats (dietary cholesterol intake not supported)
What is the best dietary way to lower cholesterol?
eat more FIBER
Which type of fiber is the key ingredient in cholesterol regulation?
soluble fiber
Why is soluble fiber important?
binds cholesterol which allows it to pass through the intestinal tract instead of being absorbed
Where does cholesterol in the body come from?
diet
synthesis by the body (liver and intestine)
What are some risk factors for high cholesterol that cannot be controlled?
age
genes
When do people’s bodies tend to produce more cholesterol?
as they AGE
T/F: A family history of high cholesterol or heart disease INCREASES a person’s risk of developing high cholesterol.
true
What are some risk factors for high cholesterol that can be controlled?
smoking
overweight
poor diet
sedentary lifestyle
How does nicotine affect cholesterol?
lowers good cholesterol (HDL)
How does cholesterol exist in the gut?
bile salts
cholesterol
Where are bile salts produced, stored and secreted into?
produced in liver
stored in gall bladder
secreted into duodenum after eating
What types of molecules are bile salts?
amphipathic
amphipathic molecules that act as a surfactant to emulsify lipids in food and form micelles containing monoglycerides, phospholipids, and cholesterol
bile salts
Which transporter is responsible for bringing cholesterol and other sterols across the membrane from the lumen into the enterocyte?
NPC1L1
What transporter is responsible for bringing non-cholesterol sterols out of the enterocyte and back into the lumen?
ABCG5/G8
What are the 5 major lipoproteins?
- chylomicrons
- VLDL
- IDL
- LDL
- HDL
large particles that carry dietary lipid
chylomicrons
carry endogenous triglyceride and some cholesterol
VLDL
carry cholesterol esters and triglycerides
IDL
carry cholesterol esters
LDL
HDL
Which pathway involves the movement of cholesterol and fatty acids from the intestine , through chylomicrons, and eventually to the liver?
exogenous
Which pathway involves the processing of various lipoproteins from VLDL to LDL
endogenous
Which pathway is responsible for forming the different types of HDL that exist?
reverse cholesterol transport
Which pathway starts with the lymph where chylomicrons are located and moves into the blood where there are lipoprotein lipases on epithelial cell surfaces on blood vessel wall that can process the chylomicrons and release FA that can be taken up by heart/muscle/adipose tissue. This produces a chylomicron remnant that gets taken up by the liver through the LDL receptor where cholesterol will be released
exogenous
Which lipoproteins are involved in the ENDOgenous pathway?
VLDL and LDL
In the endogenous pathway, where is VLDL formed?
liver from triglycerides and cholesterol esters
In the endogenous pathway,, VLDL can be hydrolyzed by lipoprotein lipase to form what?
IDL or VLDL remnants
Where do VLDL remnants go?
cleared from the circulation or incorporated into LDL
LDL particles contain a core of _____ _____ and a smaller amount of __________.
cholesterol esters
triglyceride
What is LDL internalized by?
hepatic and nonhepatic tissues
In the liver, LDL is converted into what and secreted into what?
bile salts
intestines
In non-hepatic tissues, what is the function of LDL?
hormone production
cell membrane synthesis
stored
LDL is also taken up by _______ and other cells which can lead to excess accumulation and the formation of ____ ____ which are important in plaque formation.
macrophages
foam cells
Which cells are important in plaque formation
foam cells
_____ particles, produced in the liver or the intestine, initiate the efflux of cholesterol and phospholipids from cell membranes via interaction with the _________.
Lipid-poor preβ-HDL
ATP-transporter A1 (ABCA1).
Subsequent action of the _____ esterifies cholesterol in preβ-HDL particles and converts them to mature α-HDL particles.
lecithin-cholesterol acyl transferase (LCAT)
How can mature HDL deliver cholesterol to the liver?
- directly via the Scavenger Receptor Type B1(SR-B1)
- indirectly by exchange of cholesterol esters by the cholesterol ester transfer protein to Chylomicrons, VLDL or LDL.
The uptake of apoB-rich particles occurs via ____ ___ ______(approximately 50% of RCT).
hepatic LDL Receptors
The ______ of TG in TG-rich HDL by hepatic lipase and endothelial lipase leads to a smaller HDL which re-enters the RCT cycle.
lypolysis
includes family history and HIGH LDL cholesterol
Familial Hypercholesterolemia
(F+H=FH)
(homozygotes most impacted)
Hallmark sign of homozygous FH?
orange-yellow xanthomas over knees, wrists, and interdigital webs
(deposits fo LDL cholesterol that build up in macrophages of skin)
What is the largest lipoprotein particle?
chylomicrons
float in centrifugation of blood = white, milky appearance in serum
Which particle is mostly lipid and very little protein?
chylomicrons
What is the smallest lipoprotein particle?
HDL
Which particle is 50/50 protein/lipid?
HDL
Describe the structure of a lipoprotein
- apolipoprotein wraps around surface monolayer of phospholipids and free cholesterol
- hydroPHOBIC core of triglyceride and cholesterol esters
Which lipoproteins are the most dense and smallest?
HDL
anti-atherogenic lipoproteins
Which lipoproteins cause plaques to form and contribute to coronary artery disease?
LDL, IDL, VLDL
(PRO-atherogenic lipoproteins)
-least dense and largest
When does atherosclerosis occur?
plaques of cholesterol laid down in arteries and eventually occlude artery = lack of blood supply to heart = heart attack
Progression of atherosclerosis: initial lesion
macrophage infiltration –> foam cells
drugs that block hepatic synthesis of cholesterol, but do not block intestinal uptake
statins
drugs that bind to bile and prevent intestinal uptake
bile acid resins
drugs that reduce intestinal uptake
soluble fiber
drug that requires high doses and may have serious side effects, can be used in patients who do not tolerate statins
niacin (vit B3)
drug that blocks intestinal absorption by blocking the NPC1L1 protein; most often used in combo with a statin
ezetimibe
Required functions of cholesterol in. The body:
- Major component of the myelin sheath surrounding axons and necessary for nerve transmission
- Provides the chemical backbone for synthesis of all steroid hormones like estrogens, vitamin D3, testosterone, progesterone, cortisol
- Provides the chemical backbone for synthesis of bile acids which are needed to emulsify fats in the bile.
- Component of lipid rafts and necessary for proper functioning of “coated pits” during endocytosis process
In cholesterol uptake in the gut, sterols are released from micelles and transported into cell via _____ transporter.
NPC1L1
In cholesterol uptake in the gut, once sterols have enter the enterocyte via the NPC1L1 transporter, the bulk of non-cholesterol sterols efflux back into the lumen via _____ transporters.
ABC
In cholesterol uptake in the gut, esterified cholesterol and sterols enter the _____ system via _______.
Lymphatic
Chylomicrons
Clinical importance of ABC transporters:
- Cause of drug resistance which develops in many human cancers.
- Mutation in ABC chloride carrier is cause of cystic fibrosis.
- Cause of drug resistance, which frequently develops in malaria Parasite.
- export of cholesterol out of enterocyte into lumen***
Cholesterol from extrahepatic tissues gets picked up tot eventually form HDL particle that ends up back into liver for recycling.
Reverse cholesterol transport
Individuals with FH have mutations in which receptor?
LDL
WHICH PATHWAY INVOLVES TRANSPORT OF CHYLOMICRON REMNANTS INTO THE LIVER?
Exogenous
