Cholesterol Biosynthesis and Transport Genetics Part 2 Flashcards
sodium hexametaphosphate (calgon)
developed 70+ years ago to prevent calcium deposits in pipes
prevented mineralization in plumbing
dietary lipids (fat) have low —
solubility
bile salts act as the — to emulsify dietary lipids
detergent
— is the precursor of bile salts
cholesterol
enterohepatic circulation
bile salts are reabsorbed in the GI tract for re-circulation back into the liver
a significant amount of bile salts are excreted in — every day
feces
bile salt excretion is the major way — is eliminated from the body
cholesterol
how are bile salts amphipathic?
hydrophilic: hydroxyl groups, amino acid conjugate
hydrophobic: cholesterol derived portion with methyl groups
what are the two functions of bile salts?
emulsification of lipid aggregates
solubilization and transport of lipids in aqueous environment
emulsification of lipid aggregates
bile acids have detergent action on particles of dietary fat which causes fat globules to break down or be emulsified into minute, microscopic droplets. emulsification is not digestion per se, but is of importance because it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplet s
solubilization and transport of lipids in aqueous environment
bile acids are lipid carrier and are able to solubilize many lipids by forming micelles
micelles are
aggregates of lipids such as fatty acids, cholesterol and monoglycerides that remain suspended in water
most foods that are high in cholesterol are also high in
saturated fatty acids
the current literature does not support an increased risk of cardiovascular disease and dietary cholesterol intake in healthy individuals, but foods high in saturated fatty acids and trans-fats do increase
cardiovascular disease risk
which foods can help to lower cholesterol?
oats barley whole grains beans eggplant and okra nuts vegetable oils soy fatty fish fiber supplements
soluble fiber is critical for
cholesterol intake
insoluble fiber is
regulatory (feces)
cholesterol is a major component of the — — surrounding axons
myelin sheath
cholesterol provides the chemical backbone for synthesis of all
steroid hormones
cholesterol provides the chemical backbone for synthesis of — —
bile acids
cholesterol is a component of — — and necessary for proper functioning of — — during endocytosis
lipid rafts
coated pits
SREBP 1 and 2 transcription facts controlling fatty acid and cholesterol de novo synthesis are themselves
circadian core proteins on a 24 hour cycle
cholesterol synthesis is — at night
high
ideal cholesterol
total
LDL
HDL
<170
<110
>45
high cholesterol is common in
older adults
risk factors for high cholesterol which are out of our control
age (as people age their bodies tend to produce more cholesterol)
genes ( a family history of high cholesterol or heart disease increases a persons risk of developing high cholesterol)
risk factors of high cholesterol that can be controlled include (4)
smoking
being overweight
eating a poor diet
living a sedentary life
cholesterol in the digestive system exists as either — — or —
bile salts
cholesterol
bile salts are produced in the —, stored in the —, and secreted into the — after eating
liver
gallbladder
duodenum
bile salts are amphipathic molecules that act as a surfactant to emulsify lipids in food and form micelles containing (3)
monoglycerides
phospholipids
cholesterol
— brings cholesterol across the membrane
NPC1L1
ABC transporters export cholesterol out of — and into the —
enterocyte
lumen
major lipoproteins (5)
chylomicrons VLDL intermediate density lipoprotein LDL HDL
chylomicrons carry
dietary lipid, large particles
VLDL carry
endogenous triglyceride and some cholesterol
IDL carry
cholesterol esters and triglycerides
LDL carry
cholesterol esters
HDL carry
cholesterol esters
exogenous pathway
movement of cholesterol and fatty acid from the GI tract to chylomicrons to the liver
reverse cholesterol transport
forming the different types of HCK that exists
high levels of chylomicrons circulating can lead to
atherosclerosis
exogenous pathway summary
- dietary cholesterol and fatty acids are absorbed
- triglycerides are formed in the intestinal cell from free fatty acids and glycerol and cholesterol is esterfied
- triglycerides and cholesterol combine to form chylomicrons
- chylomicrons enter the circulation and travel to peripheral sites
- in peripheral tissues, free fatty acids are released from the chylomicrons to be used as energy, converted to triglyceride or stored in adipose
- remnants are used in the formation of HDL
endogenous pathway summary
- VLDL is formed in the liver from triglycerides and cholesterol esters
- These can be hydrolyzed by lipoprotein lipase to form IDL or VLDL remnants
- VLDL remnants are cleared from the circulation or incorporated into LDL
- LDL particles contain a core of cholesterol esters and a smaller amount of triglyceride
- LDL is internalized by hepatic and nonhepatic tissues
- In the liver, LDL is converted into bile acids and secreted into the intestines
- In non hepatic tissues, LDL is used in hormone production, cell membrane synthesis, or stored
- LDL is also taken up by macrophages and other cells which can lead to excess accumulation and the formation of foam cells which are important in plaque formation.
reverse cholesterol transport summary
Lipid-poor preβ-HDL particles, produced in the liver or the intestine, initiate the efflux of cholesterol and phospholipids from cell membranes via interaction with the ATP-transporter A1 (ABCA1).
Subsequent action of the lecithin-cholesterol acyl transferase (LCAT) esterifies cholesterol in preβ-HDL particles and converts them to mature α-HDL particles.
Mature HDL can deliver cholesterol to the liver by one of two pathways:
-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 hepatic LDL Receptors (approximately 50% of RCT).
The lypolysis of TG in TG-rich HDL by hepatic lipase and endothelial lipase leads to a smaller HDL which re-enters the RCT cycle.
family history + high LDL cholesterol =
familial hypercholesterolemia (FHC)
HDL
% lipid, % protein
50, 50
chylomicrons
% lipid, % protein
99, 1
the cytoplasmic tail of the LDL receptor has a specific sequence of aa which internalize the
receptor once LDL has bound
mutations in the internalization signal prevents
internalization, so it accumulates and you dont have the negative feedback to prevent cholesterol synthesis
lipoprotein structure
surface monolayer of phospholipids and free cholesterol
hydrophobic core of triglyceride and cholesteryl esters
— are wrapped around lipoproteins
apolipoprotein
size order of lipoprotein, large to small
chylomicrons chylomicron remnants VLDL IDL LDL HDL
what do statins block?
hepatic synthesis of cholesterol, but do not block intestinal uptake
bile acid resins bind to bile and prevent
intestinal uptake
soluble fiber reduces
intestinal uptake
niacin (vitamin b3) reuires high doses and may have serious side effects, can be used in patients who do not tolerate
statins
exetimibe blocks
intestinal absorption by blocking the NPC1L1 protein. most often combined with a statin.
vytorin is a combo of simvastatin and ezetimibe in a single pill
