Lipids and Lipoproteins - Cholesterol Flashcards
Where is Acetyl CoA generated?
Mitochondria
How many Acetyl CoA are necessary to form 1 IPP (Isopentenyl Pyrophosphate)?
3
What are Isopentenyl Pyrophosphates the building blocks for?
Isoprenoids
What are 3 types of Isoprenoids?
- Steroids - ex. Cholesterol
- Fat soluble vitamins (ADEK)
- ubiquinone
How many carbons make up IPP?
5
How many carbons are in 1 Acetyl CoA?
2
How many units of IPP are needed to make a sterane (4-ring) ring?
6
Cholesterol is made of what type of ring?
Sterane (4-ring)
– From 6 units of IPP
What are the major physical features of cholesterol molecules?
Sterane ring with 27 carbons
Hydroxyl group on the 3rd carbon
Are cells able to degrade cholesterol?
NO - must be used or excreted by the liver
Biosynthesis of cholesterol is ______ proportional to the dietary intake of cholesterol
INVERSELY = the more cholesterol you eat the less you will make in your body
What is the overall reaction to make Cholesterol?
18 Acetyl CoA + 18 ATP + 16 NADPH = Cholesterol
What is the order of which products are made in phase 1 of cholesterol synthesis?
Acetyl CoA Acetoacetyl CoA HMG CoA Mevalonate Isopentenyl Pyrophosphate (IPP)
What enzyme takes Acetoacetyl CoA to HMG CoA?
HMG CoA Synthase
HMG CoA
Hydroxymethylglutaryl CoA
What enzyme takes HMG CoA to Mevalonate?
HMG CoA Reductase
What is the rate-limiting step of cholesterol synthesis?
HMG CoA (using HMG CoA Reductase and NADPH) goes to Mevalonate in phase 1
What is the order of which products are made in phase 2 of cholesterol synthesis?
6 Isopentenyl Pyrophosphates (IPPs)
Squalene
Lanosterol
Cholesterol
Once cholesterol is formed, what are its 2 options?
- Form Cholesterol Esters
2. Packaged into VLDL and sent into blood
What do Statin drugs do?
LOWER cholesterol
Where do Statin drugs work?
They INHIBIT HMG CoA Reductase enzyme (rate-limiting step)
Good side effect of Statin drugs?
Help to clear cholesterol via LDL receptor mediated endocytosis
Bad side effect of Statin drugs?
Deplete muscle levels of ubiquinone
– due to acting on pathway before IPP is generated!!
Where is cholesterol synthesis regulated?
HMG CoA Reductase enzyme
What can directly inhibit HMG CoA Reductase enzyme and thus, cholesterol formation?
- Bile acids
- Statins
- Free fatty acids
If HMG CoA Reductase enzyme is phosphorylated it is _____
INactive
If HMG CoA Reductase enzyme is DEphosphorylated it is _____
ACTIVE
What states or molecules want HMG CoA Reductase to be phosphorylated?
(INACTIVE)
Low energy states and Glucagon
What states or molecules want HMG CoA Reductase to be dephosphorylated?
(ACTIVE)
Insulin
Another way to regulate cholesterol synthesis is through transcriptional control. What protein is involved?
SREBP
SREBP binds SCAP to form a complex in the ER. What will stimulate that complex to be moved to the Golgi?
LOW cholesterol levels
Once the SREBP-SCAP complex is in the Golgi, what is formed and through what mechanism?
Mature SREBP through cleavage
What does mature SREBP bind?
SRE in the nucleus
Overall effect of mature SREBP binding to SRE in the nucleus?
INCREASED transcription of HMG CoA Reductase
SREBP
Sterol Regulatory Element Binding Protein
SCAP
SREBP - Cleavage Activating Protein
SRE
Sterol Regulatory Element
If there is increased transcription of HMG CoA Reductase, what does that cause?
- Increase in cholesterol formation
- Upregulation of LDL receptor
What will cause the SREBP-SCAP complex to be retained in the ER?
HIGH cholesterol levels – do not need to make more
