Lipoprotein Metabolism Flashcards
2 places where lipids are synthesized
Liver and intestine
How are triglycerides transported in plasma
Lipoproteins
Classifications of the lipoproteins
All same components, just different %
Chylomicrons - most fat, least protein
HDL- least fat, most protein
HDL is smallest and most dense
Give other names for the following
- VLDL
- LDL
- HDL
- Pre beta lipoprotein
- Beta lipoprotein
- Alpha lipoprotein
What is an apoprotein
Function
Protein component of a lipoprotein
Mostly present on the surface; act as surface receptors
Name where each of the following apoproteins are present:
- Apo A-1
- Apo B-48
- Apo B-100
- Apo C-II
- Apo E
- LCAT
- Chylomicrons
- VLDL and LDL
- Lipoprotein lipase activator
- IDL and chylomicrons
Difference between structure of Apo B-48 and Apo B-100
They are both from the same B gene, 48 is only 48% transcribed and 100 is 100% transcribed
List the lipoproteins in order of which has the highest cholesterol to lowest cholesterol
List them from highest TAG to lowest TAG
LDL, HDL, VLDL, chylomicrons
Chylomicrons, VLDL, LDL, HDL
HDL
- Generated by
- Function
- Liver and intestine
2. Delivers cholesterol to the liver for elimination
LDL
- Generated by
- Function
- VLDL
2. Deliver cholesterol to peripheral tissues
VLDL
- Generated by
- Function
- Liver
2. Deliver de novo TAG to peripheral tissues
Chylomicrons
- Generated by
- Function
- Intestine
2. Deliver dietary TAG to peripheral tissues
How does an immature chylomicron become mature
What is the only component that an immature already has
Acquires Apo C-II and Apo E from HDL
Immature chylomicron has Apo B48
~immature VLDL has Apo 100 and also has to acquire apo C-II and apo E
Immature chylomicrons are produced from
Dietary lipids
Once chylomicron is mature it enters circulation where it is acted on by
Lipoprotein lipase (in muscle/adipose)
Lipoprotein lipase converts chylomicron to chylomicron remnant. In this process, what does it release
Glycerol to liver (which can form DHAP), FFAs, and Apo C-II (which is returned back to HDL)
What is required in order for packaging of lipoprotein
MTP
When will serum be milky?
After a high fat meal, chylomicrons will temporarily cause serum to become milky
Chylomicron remnant is taken up by liver by
Apo E receptors
Lipoprotein lipase works on which lipoproteins
VLDL and chylomicrons
If chylomicrons are still in your blood after not eating for ~5+ hours, what does that indicate
MTP or Apo B-48 are defective
Lipoprotein lipase:
- Converts chylomicrons to
- Converts VLDL to
- Chylomicron remnant
2. IDL
What activates lipoprotein lipase
Apo C-II
Chylomicrons
- Assembled where?
- Cholesterol or cholesterol ester
- What type of apoprotein
- Where does it go once synthesized
- Intestinal mucosal cells
- Cholesterol ester
- Apo B48 and Apo E
- Lymphatic circulation
VLDL
- Assembled where?
- Cholesterol or cholesterol ester
- What type of apoprotein
- Where does it go once synthesized
- Liver cells
- Cholesterol
- Apo B-100 (essential for removal of LDL)
- Blood
Main lipid component of both chylomicrons and VLDL
TAG
Function of ACAT
Converts cholesterol to cholesterol ester
- Decreased cholesterol in the cell activates what two things?
- Inhibits what?
- LDL receptor gene expression, HMG CoA reductase
- ACAT
~opposite for increased cholesterol in cells
Deficiency of LDL receptor causes?
Increase in plasma LDL, thus an increase in plasma cholesterol
(LDL receptor aids in cellular uptake/ degradation of LDL)
When the pH of the endosomes (vesicles containing LDL) fall what happens to LDL?
After this happens, what happens to the remnant of LDL?
LDL separates from its receptor-CURL
Transferred to lysosome for degradation
What happens to free cholesterol if it is not utilized?
It becomes esterified by ACAT and stored as cholesterol ester
What is woolmans disease?
Inability to hydrolyse lysosomal cholesterol esters by cholesterol esterase
What is Niemann-Pick disease?
Inability to transport unesterified cholesterol out of the lysosomes
What is familial hypercholesterolemia (type II hyperlipidemia) what does it cause
LDL receptor deficiency (genetic or dietary); raises LDL level
Name 3 enzymes activated by free cholesterol
ACAT, LCAT, and PCAT
Function of scavenger receptor Class A (SR-A)
Endocytosis of chemically modified LDL in which lipid component or ApoB has been oxidized
VLDL and CM require what two lipoproteins?
Where do they get them from
Apo C-II and Apo E
HDL
Function of nascent HDL
What enzyme functions to do this
Take up unesterified cholesterol and esterify them
LCAT
What activates LCAT activity
Apo A1
What binds to HDL to facilitate uptake of cholesteryl esters?
How does it bind to HDL
SR-B1
Via Apo A
SR-B1 synthesis is upregulated for ?
Steroidogenesis
LCAT
- Bound to?
- Function
- What does it promote?
- HDLs and LDLs in plasma
- Esterifies cholesterol on surface of lipoprotein; cholesteryl ester moves to interior of lipoprotein
- Flux of cholesterol from cell membranes into HDL
HDL and IDL make an exchange. What is the exchange
What is needed in order to make this exchange
HDL gives cholesteryl esters to IDL
IDL gives TAG and phospholipids to HDL
CETP
Tangier disease:
- Caused by
- Will cause
- How does it present
- Defect in cholesterol transport out of cells; defects in ABC-A1
- HDL levels will be half the normal amount
- Build up of cholesterol in tonsils, liver, spleen, peripheral neurons; foam cells observed
Type I Hyperlipidemia
- Defect in?
- Biochemical findings?
- Features?
- What will it not cause
- Mortality from this is typically caused by
- LPL or Apo C-II deficiency
- Increased chylomicrons and increased TAG
- Red/orange eruptive xanthomas, fatty liver/spleen, acute pancreatitis
- Will not lead to atherosclerosis
- Pancreatitis
Type IIA Hyperlipidemia
- Defect in?
- Biochemical findings?
- Features?
- LDL receptor
- Increased LDL and increased cholesterol
- High risk of atherosclerosis, xanthomas of achilles tendon
Type IV Hyperlipidemia
- Defect in?
- Biochemical findings?
- Features?
- Insulin deficiency
- LPL will be inactive, increased TAG
- Most common hyperlipidemia, associated with obesity, DM, and alcoholism
Abetalipoproteinemia/Bassen-Kornzweig syndrome
- Defect in which protein?
- This protein is necessary for?
- Deficiency leads to lack of
- Characterized by
- Microsomal triglyceride transfer protein gene; these synthesize of beta lipoproteins
- Absorption of fat, cholesterol and ADEK
- Apo B48 and Apo B100
- Increased content of sphingomyelin and decreased content of lecithin
