Biochem - E3 Flashcards
2 Classes of lipids
- Fatty acid based
- Amphipathic, micelle forming, soaps
- Energy storage (fat deposits cushion organs & insulate against heat loss)
- Membranes (electrical insulation of nerves), including phospholipids & sphingolipids
- Signals. - Isoprenoids
- Bile Acids/Salts
- Membranes,
- Signals,
- Cofactors,
- Fat soluble vitamins.
At neutral pH, fatty acids are ____ and act as _____
Charged, soaps.
Features of short chain FAs (<6)
- Produced in colon by microbiome
- Can cross blood brain barrier
- 6-10% of total energy (80% in coloncytes)
Medium chain FAs (6-12) can be used as tx for…
Waldmann disease, epilepsy, chronic pancreatitis
Long chain FAs (>12)
Are absorbed in the small intestine
Excess carbohydrate is converted into _____ (default) or _______ (regulated) by the liver.
Excess carbohydrate is converted into FAs (default) or cholesterol (regulated) by the liver.
FAs and cholesterol are packaged into VLDL (___________) by ________& ________.
FAs & CHL are packaged into Very Low Density Lipoprotein (VLDL) via TAG synthase and acyl cholesterol acyl transferase (ACAT).
What is the characteristic apoprotein of VLDL?
Apoprotein of VLDL is Apo-B100 (formed from the same gene as B48).
After release, the ApoCII of VLDL stimulates _____________ to hydrolyze FAs for storage in ______.
After release, the ApoCII of VLDL stimulates lipoprotein lipase (LPL) to hydrolyze FAs for storage in adipose.
(The LPL enzyme projects into the lumen of capillaries in many tissues - mostly adipose tissue, muscle, and some breast tissue)
- LPL is the same enzyme that works on chylomicrons
What generates Intermediate Density Lipoprotein (IDL)?
When TAGs = Cholesterol esters (CEs), ApoC-II falls off of VLDL and forms IDL.
All cells need cholesterol to modulate ___________________.
_______ is the major serum transporter for cholesterol.
All cells need cholesterol to modulate membrane fluidity.
LDL is the major serum transporter for cholesterol.
How is LDL generated?
The liver expresses Hepatic Triglycerol Lipase (HTGL) to remove remaining TAGs from IDL to make LDL, the major transporter of cholesterol to tissues.
Does VLDL or LDL have longer half-life?
VLDL has a half-life of about 3 hours while LDL has a half-life of days.
What is the danger of LDL circulating for too long?
If LDL circulates too long, it gets oxidized, stimulates monocyte recruitment into the blood vessel wall.
Monocytes differentiate to macrophages and take up ox-LDL (via scavenger receptors).
If they take up too much –> become foam cells and die.
Dead foam cells (fatty streak), + smooth muscle cell growth (via signals from foam cells) + matrix degradation forms an atherosclerotic plaque.
A function of HDL is the promotion of cholesterol efflux from cells… why is this so useful?
Efflux of cholesterol from foam cells –> reduction in foam cell formation; macrophages may accumulate, but are not converted into foam cells.
Inflammatory process is arrested to a certain extent.
So, HDL is anti-inflammatory and also protects against the development of atherosclerosis.
HDL is released as an “empty shell” by the liver intestine. It is released with ____________ & __________, ____________ (its characteristic apoproteins). CE’s get picked up later.
HDL is released with phospholipids & ApoA-I, ApoA-II (its characteristic apoproteins). CE’s get picked up later.
Where does liver get cholesterol: synthesis, ________ ___________, mature HDL, LDL, ____________ (aka IDL).
As known as the “_____________________” pathway
Where does liver get cholesterol: synthesis, chylomicron remnants, mature HDL, LDL, VLDL remnants (aka IDL).
As known as the “reverse cholesterol transport” pathway
What is the role of Lecithin Cholesterol Acyl Transferase (LCAT) as HDL travels through the blood and encounters cells with excess cholesterol on their surfaces?
Lecithin Cholesterol Acyl Transferase (LCAT) is stimulated by ApoA-1 and transfers CHL from cell to HDL.
LCAT removes a fatty acid from a membrane phospholipid to form CEs out of the excess cholesterol that has been moved to the cell surface. The lysolecithin that is produced can be repaired .
What is the fate of HDL full of CEs?
They can be bound by Scavenger Receptor-BI (SRB1 or HDL receptor) on liver & adrenals for endocytosis & degradation.
What does a 30% increase in LDL lead to?
What about a low LDL:HDL (1.5:1 rather than 3:1)?
30% increase in LDL = 3x risk of coronary mortality
A low LDL:HDL (1.5:1 rather than 3:1) halves risk of CHD.
Cholesterol is the same in LDL and in HDL: just packaged differently
Describe the composition of chylomicrons.
Lipids (mostly TAG)»_space; protein: low density
Describe the composition of HDL
Lipids (mostly CEs) «_space;protein: high density
Arrange the post absorptive lipoproteins in order of TAG content from MOST to LEAST.
Most TAG –> Least TAG
Chylomicron, VLDL, IDL, LDL
Describe Familial Hypercholesterolemia
Defective receptor for receiving LDL (LDL-R defect leads to greatly elevated LDL).
