Sterols And Isoprenoids Flashcards
Precursors for cholesterol
Bile acid and salts
Steroid hormones
Vitamin d
Function of cholesterol
Membrane lipid
Mobility of lipids in plasma
Signaling molecules
Isoprene
5Cs
2 pi bonds
Preen tail feathers
ISO = only carbons
Intermediate between acetate and cholesterol
Cholesterol = 27 C
HMGcoA structure reminders
6 carbons
S coA plus
2 x acetyl groups
1x carboxyl group on top
3 Os
HMG = 3 letters = 3 oxygens
Mevalonate structure reminders
6C
3x acetyl coA
No phosphate
Carboxyl group
OH in middle
2 Os
Valon = talon = 2 feet = 2Os
Acetyl coA acetyl transferase
And HMGcoA synthase
Catalyze what kind of rxn?
Claisen condensation
Both actually favor acetyl coA
But unfavorable HMG product used too quickly to be reverted
HMG coA Reductase Details
Integral membrane protein of smooth ER
Uses NADPH
Major point of regulation for cholesterol synthesis
Delta 3 isopentonyl pyrophosphate structure details
5C
2P
Delta 3= double bond at 3rd carbon
ISO = isoprene
Pyro = pesto = 5
Double bond is at opposite end of phosphorous groups
1 double bond
Only oxygens are phosphorous groups
Activated isoprene
Dimethylallyl pyrophosphate structure details
5C 2P
Di = double bond on carbon 2 from phosphate groups
= in middle like lady di
No Os except for phosphates
Pryo = pento = 5
Activated isoprene
2nd phase cholesterol synthesis:
Conversion of mevalonate to 2 types of activated isoprenes
Product = 5C
Isopentonyl pyrophosphate
Dimethylallyl pyrophosphate
3ATP = 3 P addition
Good leaving group = co2 and Pi on 3rd carbon
= double bond formed
For cholesterol synthesis
What are some driving features?
Good leaving groups = CoA, pyrophosphate
Reducing power
HMG CoA reductase inhibitors
Statins
Compactin
Simvastin
Etc
Geranyl pyrophosphate structure reminders
10C
2P
Head to tail condensation product from isoprenes
Ger = geriatric = decades = 10
Farnesyl pyrophosphate structure reminders
15C
2P
Farnes = harness the Sasquatch = needed to make the Sasquatch = Squalene precursor
Squalene
30C
0P
Squalene = Sasquatch = 30 yr old myth
Myth: he does not pee!!
Isoprene derivative pathway - carbon numbers - for cholesterol
= stage 3
5C= Dimethylallyl pyrophosphate
Delta 3 isopentonyl pyrophosphate
10C = geranyl = fesyl
15 = farnesyl
30 = Squalene
Which step in stage 3 of cholesterol synthesis requires NADPH?
Squalene synthase
15C + 15C
Cholesterol synthesis
4 main steps
- Mevalonate synthesis from acetyl CoA (1 NADPH) (RLS)
- Activated isoprene synthesis from Mevalonate (3ATP)
- Squalene synthesis from 6x activated isoprenes (1 NADPH)
- Squalene cylcization and modification (1 NADPH)
Where are cholesteryl esters formed and by what enzyme?
Liver
ACAT = transfer of fatty acid acid from CoA to hydroxyl group of cholesterol
= more hydrophobic
= no longer functional in membranes
= secreted in lipoprotein particles and transported to other tissues/ stored in liver as lipid droplets
LDL
Low density lipoprotein
= carry cholesterol
= received by cells via LDL receptors
= return to liver whereas VLDL is formed in liver
If LDL high then further cholesterol synthesis is not needed = avoids cholesterol accumulation in cells
Short term regulation of cholesterol metabolism
Insulin = dephlsphorylates HMGcoA carboxylase = activated
Glucagon = deactivates
AMPK = low ATP = deactivates
Longer term regulation of cholesterol synthesis
SREBPs
= if high cholesterol / oxysterol = stay in ER with SCAP and insig
= if low = transported to golgi and cleaved = fragment to nucleus = activates transcription for HMG CoA reductase + LDL receptor (acceptance of outside cholesterol)
Statins = competitive inhibitors for HMG CoA reductase
Other isopentonyl derivatives
= isoprenoids
Vitamin KEA
Rubber
Plant hormones
Phyto chain of Chlorophyll
Protein prenylation
Proteins anchored to surfaces = biological activity
