Hyperlipidemia I Flashcards

1
Q

What is hyperlipidemia?

Why is it a concern?

What are the primary & secondary causes?

A

elevated levels of lipids int he blood (cholesterol & triglycerides)

leads to increased risk of atherosclerotic cardiovascular disease (ASCVD)

  • Primary cause: genetic conditions
  • secondary causes: environmental factors (diet, exercise etc)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the difference between the exogenous and endogenous lipoprotein metabolic pathways?

A
  • Exogenous pathway: transports dietary lipids to the periphery & the liver
  • Endogenous pathway: transports hepatic lipids to the periphery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Identify the full term for the following acronyms:

FFA

HL

IDL

LDL

LDLR

LPL

VLDL

A
  • FFA
    • free fatty acid
  • HL
    • hepatic lipase
  • IDL
    • intermediate-density lipoprotein
  • LDL
    • low-density lipoprotein
  • LDLR
    • low-density lipoprotein receptor
  • LPL
    • lipoprotein lipase
  • VLDL
    • very-low-density lipoprotein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Check out this table! Pick a section & write it down

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

check this out! Pick a section & write it down

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which lipids are transported by lipoprotein particles?

Which lipids are transported by albumin?

A
  • Lipoprotein particles
    • triglycerides
    • phospholipids
    • cholesterol & cholesterol esters
  • Albumin
    • Free Fatty Acids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are some examples of lipids?

What is a lipoprotein & provide some examples?

What is an apolipoprotein & provide some examples?

A
  • Lipids
    • cholesterol and cholestrol esters, triglyceride, fatty acids, phospholipids
  • Lipoprotein: lipid transport particles in the blood
    • chylomicron, chylomicron remnants, VLDL, IDL, LDL, HDL
  • Apolipoprotein: protein subunits of the lipoprotein particle
    • ApoB48, ApoB100, ApoC11, ApoA-1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the function of the following lipoproteins

chylomicrons

VLDLs

LDLs

HDLs

A
  • chylomicrons
    • transport dietary fat from the intestine
  • VLDLs
    • transport endogenous fat from the liver
  • LDLs
    • deliver cholesterol to liver and tissues with large cholesterol needs (adrenals, sex glands, etc.)
  • HDLs
    • transport cholesterol from membranes in tissues to IDLs which deliver cholesterol back to liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the “good cholesterol” and the “bad cholesterol” ?

A
  • Good Cholesterol
    • HDL : reverse cholesterol transporter
  • Bad Cholesterol
    • LDL: 40-50% cholesterol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Identify the indicated components of the lipoprotein particle

A
  • Core: nonpolar lipid (triglycerides & cholesterol esters)
  • Surface: phospholipids, cholesterol and other amphipathic molecules (i.e. apolipoproteins)
  • Apolipoproteins
    • some functional, some structural (as synthesizing particle)
    • activate enzymes
    • act as ligands for receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

List the lipoproteins in order from largest to smallest

Which are most bouyant?

A
  • Largest to smallest
    • chylomicrons
    • VLDL
    • IDL
    • LDL
    • HDL
  • lipoproteins that contain the highest percentage of neutral lipid (like triglyceride) are more bouyant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the relevant structural scaffold apolipoproteins? Functions?

What are the relevant apolipoproteins that activate enzymes or bind to receptors? Functions?

A
  • Structural scaffold apolipoproteins
    • Apo B-48 Chylomicrons
    • Apo B-100
      • VLDL, IDL, LDL
      • provide structure & assist in binding receptors (chylomicron remnant receptor and LDL receptor)
  • Apolipoproteins that activate enzymes or bind to receptors
    • Apo A-1
      • HDL, Chylomicrons, VLDL
      • Activates LCAT
    • Apo E
      • chylomicron remnants, VLDL, IDL, HDL
      • acquired from HDL particles in teh blood & binds to the ApoE receptor on the liver
    • ApoC-II
      • chylomicrons, VLDL, IDL, LDL
      • acquired from HDL particles in the blood, binds and activates lipoprotein in lipase in muscle and adipose tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the exogenous lipid pathway from ingestion to blood stream

A
  • Dietary Lipids (exogenous)
    • solubolized by bile salts
    • pancreatic lipase & colipase converts it to 2-momoacylglycerol (2-MG)
    • 2-MG taken up by epithelial & put back together into a triglyceride
      • add apoB & phospholipid layer
      • secreted into lymph as chylomicron
      • join the blood stream via the thoracic duct
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the endogenous lipid pathway from production to blood stream

A
  • Endogenous (liver)
    • excess fuel becomes acetyl CoA, which can be use to generate fatty acids & ultimately triglycerides
    • (VLDL) will be constructed with tryglycerides, apoB, and phospholipids & secreted by the liver directly into the blood stream becaue the liver has breaks in the endothelium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Identify what the following molecules carry, where they are made, what they are packaged with, and where they go after secretion

Chylomicrons

VLDLs

LDL particles

A
  • Chylomicrons
    • carry dietary lipid
    • synthesized by intestinal epithelial cells
    • packaged TG and dietary cholesterol with apoB-48
    • move via the lymph through the thoracic duct
  • VLDLs
    • carry endogenous lipid from the liver
    • synthesized in the liver
    • contain cholesterol de novo synthesis derived from dietary carbohydrates
    • packaged TG, cholesterol and apoB-100
    • after secretion into the blood, VLDLs are converted to IDLs and eventually LDLs
  • LDL particles
    • cholesterol-rich transport particles
    • internalized by the liver adn othe rtissues needing large amounts of cholesterol (ie. adrenals for steroid synthesis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Draw this summary

A
17
Q

Describe the transport of exogenous lipids by chylomicrons

A
  • Dietary triglycerides coming into the small intestine
  • VLDLs synthesized in epithelial cells & they go out into the lympatics
    • at this point they are nascent (Apo-B48 & Apo-A)
  • Nascent chylomicron can interact with HDL which will transfer the ApoC & ApoE making it a mature chylomicron
  • ApoC activates lipoprotein lipase when it gets to the extrahepatic tissues (adipose & muscle) that allows for the removal of triglycerides by digesting it to fatty acids (taken up by the cells) & glycerol (back to the liver)
  • After losing triglycerides, the chylomicrons become smaller, more dense & lose apoproteins at which point they are considered a chylomicron remnant
    • they will be taken up by the liver & digested
18
Q

Describe the transport of endogenous lipids via VLDL

A
  • Fatty acids converted to triglycerides, which are then packaged into VLDL
  • VLDL goes out into blood stream where it picks up CII (activate lipoprotein lipase) & E from HDL
    • Fatty acids (muscle will convert FA to CO2 + H2O & adipose will convert FA to TG stores) & glycerol will leave
  • the VLDL loses enough fatty acids, it will be converted to an IDL
    • some of the IDL will pass by the liver & endocytosed, go to lysosomes and be degraded
    • some IDL will interact with other lipases (i.e. HTGL), losing more FA & becoming LDL
      • LDL can be endocytosed by the liver, gonads or adrenals to be degaded & reused
      • If there is a lot of LDL sitting around for a while, it can sneak into the intima of the blood vessels where macrophages will try to clear it up & in the process create foam cells
19
Q

What is the major concern with the development of foam cells?

A

cells with huge amount of fat inside are the precursors for atherosclerosis

20
Q

Describe the process of LDL receptor-mediated endocytosis

A
  • Binds to the receptor in a clathrin-coated pit
  • endocytosed by pinching off membrane & creating vessicle
  • this vessicle becomes an endosome
    • receptor will enter different particle to be recycled back to the cell membrane
    • drop off the particle
  • the lipoprotein particle will join with a lysosome which will breakdown fats to FA and cholesterol (to membrane or cholesterol ester droplets), proteins to AA
  • Additional receptors are processed through the ER & golgi then sent to the membrane
21
Q

What are the 4 possible fates of endocytosed cholesterol?

A
  1. Incorporated in plama membrane
  2. Stored as cholesterol ester
  3. Used for biosynthetic purposed
    • bile salts
    • hormones
  4. Used as regulatory signal
    • inhibits HMG CoA reductase synthesis (RL step in cholesterol synthesis)
    • Inhibits LDL receptor synthesis
    • Stimulates ACAT activity
22
Q

How is cholesterol stored?

What are the two enzymes used for this conversion?

A
  • Cholesterol is stored as cholesterol ester
  • ACAT (acyl:cholesterol acyltransferase)
    • synthesized at the tissues
    • esterfires fatty acid (from fatty acyl CoA) to cholesterol in cells
    • located in the cytosol of cells that store cholesterol
  • LCAT (lecithin:cholesterol acyltransferase)
    • synthesized int eh blood
    • esterfies a fatty acid (obtained from lecithin) to cholesterol present within HDL particles
    • located in the serum
    • activated by the Apo-A1 on teh HDL particles
23
Q

What do cells do with excess cholesterol?

Why do they do this?

A

They can stick it on the outer leaflet of the plasma

  • Because as HDL (which is produced by the liver) goes by these cells, it will take up extra cholesterol from cell membranes
  • The LCAT will convert the cholesterol to a cholesterol ester
  • it will interact with a VLDL or IDL through cholesterol ester transferase protein (CETP)
    • it will trad cholesterol esters for tryglycerides or phospholipids from these molecules
  • Purposes of this exchange
    • feeding LCAT new substrate,
    • replacing what LCAT has burned making cholesterol ester
    • removing extra surface area from VLDL as you are shrinking the particle
24
Q

Nam the substates & enzymes involve in producing a cholesterol ester

A

Have to use a fresh phospholipid for every LCAT reaction (b/c always use C2)