Lipid Metabolism Flashcards
What are the three kinds of lipids?
- Triacylglycerols (fats
- Phospholipids
- Steroids
Examples of where lipids exist in our bodies?
- Adipose tissue
- Arteriosclerosis
- Cell membranes
Is Saturated fats and trans unsaturated fats less fluid than cis unsatureated fats?
Yes
What is the risk of low fluidity in trigylerceride?
Risk of artheriosclerosis
Example of Steroids?
Cholesterol, Glucocorticoid, Oestrogen, Ecdysone
What does excess cholesterol lead to?
Cardiovascular disease
What precursor is Cholesterol synthesised from?
Acetate
What are the stages of Acetate to Cholesterol?
Acetate -> Mevalonate -> Activated isoprene -> Squalene -> Cholesterol
What does the esterifcation of cholesterol yield?
Cholesteryl ester
What is difference between cholesteryl ester and cholesterol?
Cholesteryl ester is more hydrophobic than cholesterol
What are the uses of Cholesterol?
- Used in the plasma membrane
- Steroid hormone production
- Precursor for Vitamin D
Where is Cholesterol synthesised?
Liver
What is Cholesterol exported as?
- Biliary cholesterol
- Bile acids
- Cholesteryl ester
What could the lack of cholesterol in the membrane cause?
Weakness in the cell membrane
What enzyme is used to covert Acetyl-CoA to Acetoacetyl-CoA in Acetate mevalonate conversion?
What is the enzyme that coverts Acetoacetyl-CoA to HMG-CoA?
HMG-CoA synthase
What enzyme is used to convert HMG-CoA to Mevalonate?
HMG-CoA reductase
Where can HMG-CoA reductase be found?
Smooth ER
The conversion of HMG-CoA to Mevalonate is a…
Rate limiting step
How is the rate limiting step regulated in CHolesterol Biosynthesis?
- Transcriptional regulation of encoding the enzyme HMG-CoA reductase
- Hormonal regulation by insulin and glucagon
Regulation of CHolesterol Biosynthesis occurs on the cell surface too but how?
- Regulating the number of LDL receptors
What is LDL receptor?
Cholesterol carrier
What is insulin’s role in hormonal regulation?
- Activates through dephosphorylation, increases the cholesterol biosynthesis
What is glucagon’s role in hormonal regulation
Deactivates through phosphorylation, decreases cholesterol biosynthesis
High cholesterol activates ACAT. Does this this cause?
Increases esterification of cholesterol for storage
What happens if cholesterol level decreases in cells?
- Expression of the gene encoding LDL receptor increases
- LDL receptor increas
- Therefore Cholesterol uptake from the blood increases
Why does Arterioscleosis occur?
Sum dietary and biosynthesised cholesterol exceed the body’s requirement
What are the causes of excessive cholesterol?
- High dietary consumption
- Genetic disorders (
Type I Hyperlipoproteinemia
– Hypercholesterolemia
– Familial HDL deficiency)
What is the purpose of Statins?
Lower blood cholesterol levels
How does Statins lower blood cholesterol level?
- Inhibit HMG-CoA reductase by mimicking mevalonate
- Inhibits cholesterol synthesis
- Lower srum cholesterol level
What does Epinephrine or Glucagn trigger ?
Mobilization of stored triglycerides
What are the function of Chylomicrons?
- Carry dietary fatty acids for storage or consumption
Where is Chylomicrons synthesized?
- ER of small intestine epithelial cells
What are the three apolipoproteins?
- apoB-48
- apoE
- apoC-II
What is the function of ApoC-II?
Activate lipase in capillaries of adipose, heart and skeletal muscle
What happens when fatty acids are depleted from chylomicrons?
Cyhloicron remnants are absorbed by the liver
What happened to the receptors in the liver with the ApoE?
Receptors in the livr bind the ApoE in chylomicron remnants
Remnants release their cholesterol and degraded by…
Lysosomes
What happns if fatty acids and carbohydrates exceed the body’s needs?
Converted to triglyercides in the liver then packaged into VLDL
What is VLDL?
Very low desnity lipoprotein
Examples of VLDL
Cholesterol, cholesteryl esters, apoB-100, apoC-I, apoC-II, apoC-III & apoE
Where is VLDL taken?
To muscle and adipose tissue
How are VLDL Remnants are removed by?
Hepatocytes via apoE
What is LDL?
Low Density Lipoprotein
What is HDL?
High Density Lipoprotein
Where is HDL synthesize?
Liver and small intestine
What is not in HDL?
Cholesteryl ester
What is the lipoproteins in HDL?
apoA-I, apoC-I & apoC-II
What enzyme is in LCAT?
LCAT (lecithincholesterol acyl transferase)
What does LCAT covert to cholesteryl ester (mature HDL)
cholesterol & lecithin of chylomicron & VLDL remnants
What happens after HDL cholesterol is unloaded to the liver?
Transformed to bile salt
What can HDL bind to?
SR-BI (protein on plasma membrane of liver & steroidogenic cells)
What is the function of SR-BI?
Mediate selective transport of cholesterol and other lipids from the mature HDL to the tissue
What occurs when HDL is depleted?
Dissoicates and recirculates the blood stream to collect more cholesterol
What is reverse cholesterol transport?
HDL extracting cholesterol from extrahepatic tissues
What does HDL interact with in cells rich in fat?
SR-Bi
What does HDL interact with with cells rich with cholesterol
ABC1 proteins
How does Atherosclerotic lesions occur?
By injury to the endothelium, followed by the thickening of the intima
Raised LDL and oxized LDL levels in the plasma causes…
Atherosclerotic lesions (plaques)
What responses to Atherosclerotic lesions?
Plateletes, leukocytes and cytokines
Platelets derived growth factor PDGF binds to what site in pathogensis of Areriosclerosis?
Smooth muscle
How is LDL affected by Arteriosclerosis?
- Binds and degrades LDL
- LDL oxidises in the arterial initma
What happens when macrophages begin to uptake LDL?
Become foam cells and form yellow patches which soon become fatty streaks due to it being unregulated
What is Type I - Hyperlipoproteinemia?
Deficiency in lipoprotein lipase due to decreased formation of apoC-II
How does Type I – Hyperlipoproteinemia affect Chylomicron?
Chylomicron clearance is impaired and accumulate int he plasma causing hyper chylomicronemia
Why does triaglyercides and cholesterols levels increase in Type I – Hyperlipoproteinemia?
Due to too much chylomicrons
What happens when plasma triacylglycerides and cholesterol levels increase in Type I – Hyperlipoproteinemia?
Results in Xanthomas (collection of lipids in skin or tendon sheaths)
What is Hypercholesterolemia caused by?
Defective LDL receptors
What does slow clearance of LDL from circulation cause?
Increase plasma LDL, triacylglycerides and cholesterol
What is the result of increase in plasma LDL, triacyglycerides & cholesterol in Hypercholesterolemia?
Xanthomas and deposiiton of lipid in tissues
What is Familial HDL deficiency caused by?
Absence of HDL due to mutations in ABC1 protein
What occurs when having Familial HDL deficiency?
Cholesterol-depleted HDL cannot take up cholesterol from cells that lack ABC1 – HDL are thus rapidly removed
- Choleresterolesters ccumulate in the plasma and tissue
