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Flashcards in transport and Fa catabolism Deck (32):
1

what happens to excess dietary carbs

-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

VLDL

-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

ApoB100

-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

Life cycle of post - absorptive lipoproteins

-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

mechanism of LDL receptors on cells that need cholesterol

-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

lysosomal acid lipase

-has cholesterol esterase activity
-hydrolyses CE's to release FA and free cholesterol (also a TAG lipase)

7

why is LDL the bad cholesterol

-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

differentiation of monocytes into macrophages

-this is promoted by modified LDL
-this causes macrophages to release cytokines to recruit more monocyte

9

macrophage LDL take up

-macrophages have receptors that take up modified LDL
-this creates a foam cell
-these receptors are called scavenger receptors

10

macrophages and foam cells express what

-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

the good cholesterol

-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

how HDL works

-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

lecithian cholesterol acyl transferase LCAT

-adds a FA to cholesterol of a cell
-CE gets transported onto HDL
-activated by ApoA-I on HDL

14

cholesterol ester transfer protein CETP

-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

LDL/HDL balance and heart disease

-increased LDL significantly increases risk of CHD
-high HDL levels are protective and low levels increase risk

16

risk factors associated with altered HDL and LDL

-diet (high cholesterol, saturated or trans-unsat fats) --> high LDL
-smoking lowers LDL
-diabetes or obesity, high LDL
-lack of exercise = high LDL, low HDL
-genetic defs = high LDL or low HDL

17

where is most dietary and synthesized fat stored?

-in adipose cells

18

release and transport of FA's stored in adipose TAGs

1. glucagon or epinephrine activate cAMP-dependent protein kinase
2. phosphorylated hormone sensitive lipase (or TAG lipase) hydrolyzes adipose TAGs to FAs
3. free FA's are transported on serum albumin and passively transported into cells for oxidation

19

note on albumin capacity

-limited and cant handle load after a fat rich meal
-cant transport cholesterol or fat soluble vitamins

20

for catabolism, TAG's must be

-activated by FA CoA synthetase which adds CoA
-it can then be used in TAG synth or beta ox

21

carnitine

-shuttles long chain activated FA's into the mitochondria matrix

22

controls on FA oxidation

-CAT 1 is inhibited by malonyl-CoA (the precurso for de novo FA synthesis)
-High AMp activates AMP deendent kinase which phosphorylates and inhibtis the enzyme that makes malonyl CoA
-rate of transport is regulated by carnitine levels

23

oxidation occurs on what carbon

beta
-and repeats until FA is all acetyl CoA

24

how many cycles of beta ox in one FA

(#C)/2-1

25

VLCAD

-14-20 carbons

26

LCAD

-12 to 18 Cs

27

MCAD

6 to 12 Cs

28

SCAD

6 or fewer Cs

29

fat versus carbs

-fats store much more energry per gram
-2.5 when dehydrated and 4 when hydrated glycogen

30

alpha oxidation

-deals with branched chain fatty acids
-phytanic acids from plants
-rare deficiency in alpha oxidation leads to build up of phytanic acids in the brain, and neurological disorders refsums disease

31

beta oxidation of very long chain FAs

-waxes
-is done in peroxisomes
-first oxidation generates hydrogen peroxide and is eliminated by catalase

32

zellweger syndrom

-cell lacks peroxisomes and very long chain FAs build up in tissues