Cholesterol

Question 1

What does cholesterol look like, as a molecule?

Answer 1

Four rings (three hexose, one pentose) with a hydrophobic arm

The hydrophobic arm distinguishes cholesterol from steroid hormones

Question 2

Cholesterol

Answer 2

Waxy fat (lipid) carried through blood by lipoproteins

HDL (high density lipoproteins)
LDL (low density lipoproteins)

Question 3

Which is the “bad” cholesterol?

Answer 3

LDL

Question 4

Which is the “good cholesterol”?

Answer 4

Unclear! LDL is bad, but HDL might not necessarily be good. Most statins, though, decrease LDL while slightly increasing HDL.

Question 5

What is the MAJOR carrier of cholesterol in the blood?

Answer 5

LDL, unfortunately

Question 6

Lipoprotein Subclasses

Answer 6

HDL (about 10 nM diameter)
LDL (20 nM)
VLDL (50 nM)
chylomicron remnant (100+ nM)
chylomicron (1000 nM! huge!)

Question 7

Anatomy of a lipoprotein

Answer 7

VESICLE Surface: Unesterified cholesterol, phospholipids, apoproteins

VESICLE Interior: Cholesterol Ester

Question 8

Cholesterol Cycle (step by step)

Answer 8

1. Apoproteins on LDL surface attracted to cell receptors.
2. LDL attaches to cell receptors on clathrin-coated pit.
3. Endocytosis creates clathrin-coated vesicle.
4. Clathrin triskelions jettisoned and returned to cell surface.
5. pH 5 endosome pinches off LDL receptors, which are recycled and returned to cell surface.
6. Endosome becomes lysosome, which breaks down and releases amino acids and fatty acids.
7. Cholesterol ester droplet taken to ER.

Question 9

Feedback Loops in Cholesterol Cycle

Answer 9

INCREASE in intracellular cholesterol leads to DECREASE in:

1. LDL receptors
2. HMG-CoA reductase

Question 10

What is the source of amino acids released from the cholesterol cycle?

Answer 10

Apoproteins on the surface of LDL vesicle

Question 11

How many mutant alleles are typically seen in the gene encoding the LDL receptor?

Answer 11

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.

Question 12

What is the SM for cellular synthesis of cholesterol?

Answer 12

Acetyl CoA

Question 13

HMG-CoA Reductase

Answer 13

The enzyme that catalyzes the rate-limited step in cholesterol biosynthesis

(HMG-CoA to mevatonate)

Question 14

What’s the best way to inhibit the biosynthesis of cholesterol?

Answer 14

Inhibit HMG CoA Reductase

Question 15

Statin

Answer 15

A class of drugs that acts as inhibitors of HMG CoA Reductase

Can act as either the substrate (HMG CoA) or the product (mevatonate)

Question 16

In what ways do statins resemble the substrate / product of the rate-limited step?

Answer 16

They have the same group but are WAY bigger

This gives them more interactions with the enzyme and stronger binding energy

Question 17

Are statins extremely different from one another?

Answer 17

No - they all have only one or two groups’ difference

Question 18

How do statins affect LDL, HDL, and TG (triglycerides)?

Answer 18

All statins decrease LDL and increase HDL

They have variable effects on TG

Question 19

Possible complication of statins

Answer 19

Rhabdomyolysis

The inappropriate breakdown of muscle, releasing myoglobin into the blood, resulting in kidney failure (eek!)