transport and Fa catabolism Flashcards
1
Q
what happens to excess dietary carbs
A
- used in fatty acid synthesis (default)
- used in cholesterol synth (regulated)
- both of these paths feed into a process of packaging TAGs and CEs into very low density lipoprotein (VLDL)
- VLDL is the transported in the blood to fat cells (TAG storage) and to tissues that need FAs or cholesterol
2
Q
VLDL
A
- very low density lipoprotein
- similar to chylomicrons but made in the liver
- their characteristic apoprotein is ApoB100 (not B48!!)
- apoproteins C and E are transferred to it from HDL after release from hepatocytes (just like chylomicrons
3
Q
ApoB100
A
- derived from same gene as ApoB48 by RNA editing
- ApoB100 is the standard translation product of the RNA transcript, ApoB48 is the edited form of the RNA, this happens in the intestine creating an earlier stop codon
4
Q
Life cycle of post - absorptive lipoproteins
A
- VLDL to IDL to LDL
- each conversion yields fatty acids
- VLDL to IDL uses Apo C-II which stimulates LPL (hydrolyzes TAGs to FA’s), Apo-C-II is then lost
- IDL to LDL uses Apo E in conjugation with HTGL to promote further TAG loss
5
Q
mechanism of LDL receptors on cells that need cholesterol
A
- LPL binds ApoB100 resulting in endocytosis and hydrolysis of CEs and apoB100
- normal half life of LDL is about 3 days
- this is the same process that degrades chylomicron remnants bound by LRP in hepatocytes
6
Q
lysosomal acid lipase
A
- has cholesterol esterase activity
- hydrolyses CE’s to release FA and free cholesterol (also a TAG lipase)
7
Q
why is LDL the bad cholesterol
A
- in excess, it gets oxidized in the blood
- these modified LDL molecules stiimulate endothelial cells to recruit monocytes
- endothelial cells express monocyte chemotactic protein 1 that attracts monocytes
8
Q
differentiation of monocytes into macrophages
A
- this is promoted by modified LDL
- this causes macrophages to release cytokines to recruit more monocyte
9
Q
macrophage LDL take up
A
- macrophages have receptors that take up modified LDL
- this creates a foam cell
- these receptors are called scavenger receptors
10
Q
macrophages and foam cells express what
A
- growth factors and proteinases
- foam cells form fatty streak and release MMP’s and growth factors that promote smooth muscle cell growth
- results in atherosclerotic plaque that restricts blood flow and can rupture to cause sudden block
11
Q
the good cholesterol
A
- HDL
- promotes cholesterol efflux
- cholesterol in foam cells is sent out of the intma and into the vessel lumen
- this decreases the inflammatory response triggered by macrophages
12
Q
how HDL works
A
- released as an empty shell by the liver and intestine (containing only membrane components and apoproteins A,C, and E)
- transfers Apo CII and E to other lipoproteins such as VLDL
- removes excess cholesterol from cell surfaces
- binds to scavenger receptor BI on liver and adrenals for endocytosis and degradation
13
Q
lecithian cholesterol acyl transferase LCAT
A
- adds a FA to cholesterol of a cell
- CE gets transported onto HDL
- activated by ApoA-I on HDL
14
Q
cholesterol ester transfer protein CETP
A
- used by HDL to indirectly shuttle cholesterol to LDL
- transfers cholesterol ester from HDL to VLDL or LDL in exchange for TAG’s
- TAG’s in HDL can be hydrolyzed by HTGL
- Alternatively the HDL gets taken up by the SR-BI receptor of the liver
15
Q
LDL/HDL balance and heart disease
A
- increased LDL significantly increases risk of CHD
- high HDL levels are protective and low levels increase risk
