Cholesterol

Question 1

what is cholesterol made of

Answer 1

lipids –> broken down into isoprenoid structure

isoprenoids: repeating 5-C structural units

cholesterol: steroid made from 6 isoprene units
–> 4 fused rings with various substituents
-streoids with hydroxy group at C3= sterols (i.e. cholesterol)

Question 2

where is cholesterol synthesized

Answer 2

diet and synthesis (in the ER) with in the body (liver and kidney)

Question 3

4 steps of cholesterol synthesis

Answer 3

1. condensation of acetyl CoA into mevalonate
2. formation of isopentenyl pyrophosphate
3. creation of squalene (uses 6 isopentenyl pyrophosphates)
4. cyclization of squalene into cholesterol

Question 4

cholesterol synthesis step 1

1. condense 3 acetyl CoA into mevalonate

what is the importance of this step? what enzyme is used?

Answer 4

rate limiting step –> main regulatory enzyme - HMG-CoA reductase

Question 5

cholesterol synthesis step 2

2. convert mevalonate into activated isoprenes

Answer 5

-add 3 phosphate groups to mevalonate (from ATP)
-immediately removed 1 phosphate
-form isopentenyl pyrophosphate

Question 6

cholesterol synthesis step 3

3. condense 6 activated isoprene units into what molecule?

Answer 6

squalene

Question 7

cholesterol synthesis step 4

4. ring closure

Answer 7

linear squalene into cyclic cholesterol

Question 8

what is the regulatory step in cholesterol synthesis?

Answer 8

-HMG CoA reductase (integral membrane protein in smooth ER); the first step in which 3 acetyl CoA are condensed into mevalonate

Question 9

what group do steroids have C3 which makes them a sterol (i.e. cholesterol?

Answer 9

hydroxy

Question 10

genetically how is HMG CoA reductase regulated in the making of cholesterol?

Answer 10

-inhibited by high levels of intracellular cholesterol (which block transcription of HMG CoA reductase gene)
–> only transcribed and translated with low intracellular cholesterol levels

-high intracellular cholesterol levels also promotes esterification of cholesterol for storage in the cell

Question 11

how is HMG- CoA reductase covalently modified to regulate cholesterol synthesis? what two sugar related molecules do this covalent modification?

Answer 11

-reversible
-HMG CoA usually in inactive, phosphorylated state
–>insulin dephosphorylates it= activate enzyme= cholesterol synthesis
-glucagon phosphorylates it= inhibit enzyme= no cholesterol synthesis