lecture 8: cholesterol synthesis

Question 1

what is the common factor of cholesterol-containing foods?

Answer 1

animal sources - comes from liver

Question 2

cholesterol fluidity

Answer 2

increases fluidity in colder temperatures
decreases fluidity in warmer temperatures

Question 3

atherosclerosis

Answer 3

thickening of arteries from deposition of cholesterol and cholesterol lipoproteins in arteries

Question 4

chylomicrons

Answer 4

transport dietary lipids throughout the body

Question 5

how does the liver repackage cholesterol? how is it taken up?

Answer 5

repackage from chylomicrons into VLDL > IDL, LDL
most tissues take up LDL as cholesterol source

Question 6

cholesterol synthesis site

Answer 6

liver and intestine are major sites
occurs in the cytosol, closely associated with ER

Question 7

substrate for cholesterol synthesis

Answer 7

acetyl-CoA

Question 8

conversion of acetyl-CoA to mevalonate

Answer 8

three 2C acetyl-CoA condensed to form 6C HMG-CoA

HMG-CoA reductase to mevalonate

Question 9

cholesterol synthesis steps

Answer 9

conversion of acetyl-CoA to mevalonate
mevalonate to isoprenoids (5C)
isoprenoids to squalene, cholesterol, lanosterol

intermediates reduced by NADPH

Question 10

primary target of cholesterol regulation

Answer 10

HMG-CoA reductase (controls production of melavonate)

Question 11

HMG-CoA reductase

Answer 11

anchored to ER membrane
negative feedback from mevalonate and cholesterol
inhibited by statins (lipid lowering drugs)

Question 12

sterol regulatory element-binding protein (SREBP) and regulation of transcription

Answer 12

sterol regulatory element (SRE) controls transcription, bound by SREBP to promoter region of genes

SREBPs induce transcription of genes involved in cholesterol metabolism and TAG/FA synthesis

Question 13

when cholesterol levels in ER membrane is low…

Answer 13

SCAP (SREBP cleavage-activating protein) binds to component of COPII coat proteins > vesicles bud off ER and sent to golgi
SREBP cleaved, releasing active form

Question 14

when cholesterol levels are high…

Answer 14

cholesterol binding to SCAP causes SCAP to bind to Insig > prevents SCAP from interacting with COPII (cannot be sent to golgi, active SREBP not released)

Question 15

HMG-CoA reductase degredation

Answer 15

high cholesterol > HMG-CoA reductase binds to insig > ubiquitination and proteosomal degradation

Question 16

HMG-CoA reductase phosphorylation

Answer 16

phosphorylates via AMPK
active when AMP levels are high (low energy charge) > makes HMG-CoA reductase less active

Question 17

how is cholesterol transported through the blood?

Answer 17

inside lipoprotein particles (HDL, IDL, LDL, VLDL, chylomicrons)

Question 18

similarities btw FA synthesis and cholesterol synthesis

Answer 18

acetyl-CoA is the building block

require a series of condensation, decarboxylation, and reduction reactions

intermediates reduced by NADPH