Cholesterol Flashcards
What does cholesterol look like, as a molecule?
Four rings (three hexose, one pentose) with a hydrophobic arm
The hydrophobic arm distinguishes cholesterol from steroid hormones
Cholesterol
Waxy fat (lipid) carried through blood by lipoproteins
HDL (high density lipoproteins)
LDL (low density lipoproteins)
Which is the “bad” cholesterol?
LDL
Which is the “good cholesterol”?
Unclear! LDL is bad, but HDL might not necessarily be good. Most statins, though, decrease LDL while slightly increasing HDL.
What is the MAJOR carrier of cholesterol in the blood?
LDL, unfortunately
Lipoprotein Subclasses
HDL (about 10 nM diameter) LDL (20 nM) VLDL (50 nM) chylomicron remnant (100+ nM) chylomicron (1000 nM! huge!)
Anatomy of a lipoprotein
VESICLE Surface: Unesterified cholesterol, phospholipids, apoproteins
VESICLE Interior: Cholesterol Ester
Cholesterol Cycle (step by step)
- Apoproteins on LDL surface attracted to cell receptors.
- LDL attaches to cell receptors on clathrin-coated pit.
- Endocytosis creates clathrin-coated vesicle.
- Clathrin triskelions jettisoned and returned to cell surface.
- pH 5 endosome pinches off LDL receptors, which are recycled and returned to cell surface.
- Endosome becomes lysosome, which breaks down and releases amino acids and fatty acids.
- Cholesterol ester droplet taken to ER.
Feedback Loops in Cholesterol Cycle
INCREASE in intracellular cholesterol leads to DECREASE in:
- LDL receptors
- HMG-CoA reductase
What is the source of amino acids released from the cholesterol cycle?
Apoproteins on the surface of LDL vesicle
How many mutant alleles are typically seen in the gene encoding the LDL receptor?
ONE. Two mutations would be fatal. Cholesterol would not be taken up by cells and so would circulate in blood. Heart attacks seen even in children.
What is the SM for cellular synthesis of cholesterol?
Acetyl CoA
HMG-CoA Reductase
The enzyme that catalyzes the rate-limited step in cholesterol biosynthesis
(HMG-CoA to mevatonate)
What’s the best way to inhibit the biosynthesis of cholesterol?
Inhibit HMG CoA Reductase
Statin
A class of drugs that acts as inhibitors of HMG CoA Reductase
Can act as either the substrate (HMG CoA) or the product (mevatonate)
In what ways do statins resemble the substrate / product of the rate-limited step?
They have the same group but are WAY bigger
This gives them more interactions with the enzyme and stronger binding energy
Are statins extremely different from one another?
No - they all have only one or two groups’ difference
How do statins affect LDL, HDL, and TG (triglycerides)?
All statins decrease LDL and increase HDL
They have variable effects on TG
Possible complication of statins
Rhabdomyolysis
The inappropriate breakdown of muscle, releasing myoglobin into the blood, resulting in kidney failure (eek!)
