Cholesterol Metabolism

Question 1

cholesterol purpose

Answer 1

maintains cell membrane

makes steroid hormones, bile acids, and vitamin D

Question 2

cholesterol synthesis aka

Answer 2

mevalonate pathway

Question 3

cholesterol synthesis location

Answer 3

smooth endoplasmic reticulum

Question 4

cholesterol synthesis step 1

Answer 4

2 acetyl-CoA to acetoacetyl-Coa
enzyme: thiolase
releases CoASH

Question 5

cholesterol synthesis step 2

Answer 5

acetoacetyl-Coa to HMG-Coa + free CoA
enzyme: HMG-CoA synthase
acetyl-CoA becomes CoASH

Question 6

cholesterol synthesis step 3

Answer 6

HMG-CoA to mevalonate
enzyme: HMG-CoA reductase
2 NADPH +2 H+ to 2 NADP+
releases CoA-SH and H2O

Question 7

rate limiting step of cholesterol synthesis

Answer 7

HMG-CoA reductase step

Question 8

cholesterol synthesis step 4

Answer 8

mevalonate to 5-pyrophosphomevalonate
enzyme: mevalonate kinase AND phosphomevalonate kinase
Each one turns 1 ATP to 1 ADP
Activation of mevalonate!

Question 9

cholesterol synthesis step 5

Answer 9

5-pyrophosphomevalonate to isopentenyl pyrophosphate
enzyme: Enzyme: pyrophosphomevalonate decarboxylase
ATP + H2O to ADP + Pi + CO2

Question 10

After step 5

Answer 10

isopentenyl pyrophosphate eventually becomes 2 farnesyl pyrophosphate (15 Carbons), then squalene (30 Carbons)

Question 11

What happens to squalene?

Answer 11

squalene is cyclized to cholesterol

oxygen is being reduced, lots of electron carriers being reduced, lots of energy used

Question 12

where is majority of cholesterol made and used?

Answer 12

the liver!

makes bile acids

Question 13

where are bile acids stored?

Answer 13

bile acids stored in gallbladder and released into intestine when need during digestion for fat digestion

Question 14

how does cholesterol move through the bloodstream?

Answer 14

it needs lipoproteins bc it is insoluble in water

Question 15

lipoproteins

Answer 15

part lipophilic and part hydrophilic

Question 16

can all cells make cholesterol?

Answer 16

yes, they can all make it for themselves

Question 17

what other organs use cholesterol?

Answer 17

adrenal glands and gonads use cholesterol to make steroid hormones

Question 18

where are isoprenes used?

Answer 18

all over: lots of uses

Question 19

when do we want to turn off the cholesterol pathway?

Answer 19

never!

Question 20

what type of molecule is farnesyl pyrophosphate?

Answer 20

a polyisoprene

Question 21

how is farnesyl pyrophosphate used?

Answer 21

lipids links for proteins
tail for ubiquinone
modified nucleotides

Question 22

methods of cholesterol regulation

Answer 22

1) HMG-CoA reductase

2) allosteric effects by covalent modification

Question 23

HMG-CoA reductase control

Answer 23

short-term: by energy competitors, allosteric binding and hormone effects
long-term: synthesis and degradation

Question 24

HMG-CoA reductase kinase aka

Answer 24

AMPK

Question 25

HMG-CoA reductase is active when

Answer 25

it is not phosphorylated

Question 26

HMG-CoA reductase is inactive when

Answer 26

it is phosphorylated

Question 27

Low energy leads to

Answer 27

decreased HMG-CoA reductase and decreased cholesterol synthesis

Question 28

AMPK is activated by

Answer 28

high AMP aka low ATP and low energy

Question 29

what enhances effect of energy regulation?

Answer 29

presence of cAMP

Question 30

what does cAMP do

Answer 30

decreases phosphatase activity which decreasing activating activity of AMPK

Question 31

in low energy,

Answer 31

liver won’t synthesize cholesterol

Question 32

in high energy,

Answer 32

liver will synthesize cholesterol

Question 33

HMG-CoA reductase levels

Answer 33

Cholesterol in LDL and mevalonate control the synthesis and degradation of the enzyme resulting in changes of up to 200-fold

Question 34

what can we make from cholesterol?

Answer 34

1) steroid hormones
2) vitamin D (in the presence of UV light)
3) bile acids/bile salts