Cholesterol

Question 1

Bile Salts

Answer 1

detergents that facilitate dietary lipid absorption in the intestines (large amount required)

Question 2

Cholesterol is a precursor to what molecules?

Answer 2

Bile Salts, steroid hormones (andro/estro) (adrenal), vitamin D3

Question 3

Total Body cholesterol amount?

Answer 3

~50g

Question 4

T or F: We make more cholesterol than we ingest from diet?

Answer 4

TRUE

Question 5

Atherosclerosis

Answer 5

narrowing and hardening of arteries due to plaque (aggregate of cholesterol, fat, calcium, fibrin)

Question 6

T or F: people with higher cholesterol concentration have higher chance of atherosclerosis?

Answer 6

TRUE

Question 7

How is cholesterol synthesized in the body?

Answer 7

1. two Acetyl CoA are combined to produce HMG-CoA
2. HMG-CoA reductase converts HMG-CoA to mevalonate (KEY REGULATORY STEP - STATINS AND BIOLOGICALLY)
3. Mevalonate is converted to 5-C isoprene building blocks
4. Isoprene building blocks are combined to get a long chain (squalene)
5. Squalene is cyclized to get ring structure, then decorated and adorned for final cholesterol structure

Question 8

What is the key regulatory point in Cholesterol synthesis?

Answer 8

HMG-CoA reductase

Question 9

How is cholesterol transported in the body?

Answer 9

Must be packaged - cholesterol esterification (storage form)

Question 10

What are the lipoproteins that transport cholesterol?

Answer 10

1. chylomicron - least dense; moves dietary fat from GI to liver/body
2. VLDL - moves fats from liver to body
3. LDL - VLDL after removal of fat; only cholesterol left; moves cholesterol from liver to body
4. HDL - cholesterol from body to liver

Question 11

LDL

Answer 11

low density lipoprotein; VLDL after removal of fat; only cholesterol left; moves cholesterol from liver to body; correlation of more LDL makes it more likely to have heart disease;

Question 12

LDL receptor sequence

Answer 12

receptor on surface, when binds it is endocytose; lysosome fuses with endosome and hydrolyzes the content; receives AA, FA, and cholesterol for absorption; LDL receptor gets recycled back onto surface

Question 13

HDL

Answer 13

high density lipoprotein; cholesterol from body to liver; correlation of more HDL makes it less likely to have heart disease

Question 14

Familial Hypercholesterolemia

Answer 14

autosomal codominant; extremely high cholesterol; “tendon xanthomas - hallmark sign of biochem dysfunctions; homozygote = high LDL; heterozygote = half as high; LDL receptor is broken, LDL not taken up from blood

Question 15

Sterol Regulatory element-binding proteins (SREBPs)

Answer 15

transcription factor that binds to SRE to promote transcription of LDL and HMG-CoA reductase

Question 16

SREBP/SCAP Complex w/ high cholesterol

Answer 16

SCAP in the ER detects when cholesterol inside the cell is high and binds to SREBP, holding it in the ER and preventing expression of the LDL receptor and HMG-CoA reductase

Question 17

SREBP/SCAP Complex w/ low cholesterol

Answer 17

SCAP releases SREBP, which moves to the Golgi and is cleaved, freeing the transcription factor. Leads to expression of LDL receptor and HMG-CoA reductase

Question 18

Statins

Answer 18

inhibitors of HMG-CoA reductase; block synthesis of cholesterol;

Question 19

Statin mechanism of action

Answer 19

taken up by liver and partially blocks cholesterol synthesis there (does not affect peripheral tissue); SREBP system in liver increases transcription of LDL receptor; extra LDL receptors allow more absorption of cholesterol from plasma; 35-45% decrease in LDL

Question 20

Statin Effects

Answer 20

cholesterol deposits in coronary arteries no longer expand; lowering of second heart attacks in patients with heart disease; may prevent first heart attacks in pts w/ high cholesterol; improvement in circulatory system

Question 21

Statins Adverse Effects

Answer 21

Muscle pain, risk of TIIDM

Question 22

PCSK9

Answer 22

Bind to LDL receptors and directs them towards degradation

Question 23

PCSK9 Inhibitors

Answer 23

inhibit PCSK9 = increased LDL receptors = lower blood cholesterol; available therapeutic - 40-70% reduction of LDL w/ statins