Lipid metabolism Flashcards
What are the different types of lipids?
- Fatty acids
- Triglycerides
- Cholesterol
- Phospholipids
- Steroids
- Glycolipids
What males a triglyceride?
3 FAs and 1 Glycerol
Name the different types of lipoproteins
- Chylomicrons
- VLDL
- IDL (intermediate density)
- LDL (low density)
- HDL
What are the largest lipoproteins?
Chylomicrons
What are the smallest lipoproteins?
HDL
What are the functions of apolipoproteins?
Where are they found?
Found in lipoproteins
- Bind lipids
- Act as surface receptors
- Co-factors for enzymes
How are fatty acids absorbed in the GI tract?
Converted to fatty acids
- Packaged into chylomicrons by intestinal cells
What is cholesterol converted into in the enterocytes?
Cholesteryl esters
What converts cholesterol into cholesterol esters in the enterocytes?
Acyl-CoA cholesterol acyltransferase (ACAT)
What are Cholesteryl esters packaged into to enter the lymph?
Chylomicrons
What does ACAT add to the cholesterol to create a cholesteryl ester?
Fatty acid
What can be found insode chylomicrons?
- Triglycerides
- Vitamins (ADEK)
- Cholesteryl esters
What apolipoprotein found on chylomicrons is required for secretion from their enterocytes?
Apolipoprotein B48
How much apo-B protein is contained on apolipoprotein B48?
48%
Where is Lipoprotein lipase found?
Extracellularly
- Adipose tissue, muscle and heart
- Anchored to capillary walls
What tissue does not contain Lipoprotein lipase?
- What does it contain instead?
Not in Liver
- Hepatic lipase instead
What is the function of lipoprotein lipase?
Converts triglycerides into fatty acids (and glycerol)
- Shrinks chylomicrons by removing the fatty acids from triglycerides
What does lipoprotein lipase require for activation?
Apo C-II
- Found on chylomicron particles, VLDL/IDL
Where is Apo E found and what is its function?
- Binds to liver receptors
- Required for uptake of remnants
What apoplipoproteins are secreted from HDL and given to chylomicrons?
- Apo C-II
- Apo E
What does the chylomicron become and what organ does it go to after Lipoprotein lipase has offloaded its fatty acids to muscle and adipose tissue?
Becomes a chylomicron remnant and is transported to the liver
Chylomicron remnants are able to be taken up by the liver through expression of what receptors?
Apo-E
- ApoE receptors are able to take up remnants via receptor-mediated endocytosis
When are chylomicron remnants present?
After meals (clear 1-5 hrs)
What appearance do chylomicron remnants have?
Milky
What is the only organ that can synthesise cholesterol?
Liver
What enzyme combines Acetyl-CoA and Acetoacetyl-COA to make HMG-CoA?
HMG-CoA Synthase
- Occurs in liver
What enzyme converts HMG-CoA to Mevalonate?
HMG-CoA Reductase
liver
Mevalonate eventually gets converted to what in the liver?
Cholesterol
Why can high levels of HDL be associated with lower levels of cardiovascular disease?
It is scavenger lipoprotein
- It brings cholesterol back to the liver from the periphery
HDL contains the enzyme LCAT (Lecithin-cholesterol acyl transferase) what does this do?
Esterifies cholesterol in HDL; packs esters densely in core
What is LCAT activated by in HDL?
A-I
What is the function of CETP (Cholesteryl ester tranasfer protein)?
Exchanges esters (HDL) for triglycerides (VLDL) - Allows HDL to take some of the triglycerides from VLDL particles
What is the purpose of VLDL?
Carries triglycerides, cholesterol to tissues from liver
What is VLDL secreted by?
VLDL (with only B-100)
VLDL pciks up Apo E and C-II from what?
HDL
What enzymes act on VLDL in circulation to remove triglycerides?
- LPL removes triglycerides
- CETP in HDL removes triglycerides
What does VLDL become after the removal of many triglycerides by LPL and CETP?
IDL
What acts on IDL to make it become LDL?
- Hepatic lipase removes triglycerides
- HDL removes and acquires C-II and ApoE from IDL
What is the function of hepatic lipase?
found in liver capillaries
Similar function to LPL (releases fatty acids)
- Important for IDL -> LDL conversion
What is contained inside LDL?
- Small amount of triglycerides
- High concentration of cholesterol / cholesterol esters
Where does LDL transfer cholesterol to?
Cells with LDL receptors
What do the cells with LDL receptors recognise on the LDL?
B100
What are foam cells?
Macrophages filled with cholesterol
- Contain LDL receptors and LDL
- Found in atherosclerotic plaques
What is lipoprotein a a modified form of?
LDL
What large glycoprotein is contained in lipoprotein a?
Apo A
High levels of lipoprotein a indicate what?
Risk of CV disease
- Not routinely measured
- No proven therapy
What is abetalipoproteinemia a defect of?
MTP
- Microsomal triglyceride transfer protein
How is abetalipoproteinemia inherited?
AR
What proteins/structures are affected in abetalipoproteinemia?
Lipoproteins w. apoB
- Chylomicrons from intestine (B48)
- VLDL from liver (B100)
What are the effects of abetalipoproteinemia in respect to lacking chylomicrons (B48) and VLDL (B100)?
Chylomicrons (B48)
- Lipids accumulate in intestine
- ADEK not absorbed
VLDL from liver (B100):
- Lack of VLDL, IDL, LDL in plamsa
What are the clinical features of abetalipoproteinemia
Infancy
- Steatorrhea
- Abdo distension
- Failure to thrive
Vitamin deficiencies
- Vit E (ataxia, weakness, hemolysis)
- Vit A - Poor vision
What will be seen on biopsy in abetalipoproteinemia?
Lipid accumulation in enterocytes (cannot leave via chylomicrons)
What are the lab findings in abetalipoproteinemia?
- Low or zero VLDL/IDL/LDL
- Very low triglyceride and total cholesterol levels
- Low vit E
- Acanthocytosis (abnormal RBC membrane lipids)
