Sterols And Isoprenoids Flashcards

1
Q

Precursors for cholesterol

A

Bile acid and salts
Steroid hormones
Vitamin d

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2
Q

Function of cholesterol

A

Membrane lipid
Mobility of lipids in plasma
Signaling molecules

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3
Q

Isoprene

A

5Cs
2 pi bonds
Preen tail feathers
ISO = only carbons

Intermediate between acetate and cholesterol
Cholesterol = 27 C

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4
Q

HMGcoA structure reminders

A

6 carbons
S coA plus
2 x acetyl groups
1x carboxyl group on top
3 Os
HMG = 3 letters = 3 oxygens

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5
Q

Mevalonate structure reminders

A

6C
3x acetyl coA
No phosphate
Carboxyl group
OH in middle
2 Os
Valon = talon = 2 feet = 2Os

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6
Q

Acetyl coA acetyl transferase
And HMGcoA synthase
Catalyze what kind of rxn?

A

Claisen condensation

Both actually favor acetyl coA
But unfavorable HMG product used too quickly to be reverted

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7
Q

HMG coA Reductase Details

A

Integral membrane protein of smooth ER

Uses NADPH

Major point of regulation for cholesterol synthesis

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8
Q

Delta 3 isopentonyl pyrophosphate structure details

A

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

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9
Q

Dimethylallyl pyrophosphate structure details

A

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

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10
Q

2nd phase cholesterol synthesis:
Conversion of mevalonate to 2 types of activated isoprenes

A

Product = 5C
Isopentonyl pyrophosphate
Dimethylallyl pyrophosphate

3ATP = 3 P addition
Good leaving group = co2 and Pi on 3rd carbon
= double bond formed

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11
Q

For cholesterol synthesis
What are some driving features?

A

Good leaving groups = CoA, pyrophosphate

Reducing power

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12
Q

HMG CoA reductase inhibitors

A

Statins
Compactin
Simvastin
Etc

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13
Q

Geranyl pyrophosphate structure reminders

A

10C
2P

Head to tail condensation product from isoprenes
Ger = geriatric = decades = 10

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14
Q

Farnesyl pyrophosphate structure reminders

A

15C
2P

Farnes = harness the Sasquatch = needed to make the Sasquatch = Squalene precursor

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15
Q

Squalene

A

30C
0P

Squalene = Sasquatch = 30 yr old myth
Myth: he does not pee!!

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16
Q

Isoprene derivative pathway - carbon numbers - for cholesterol
= stage 3

A

5C= Dimethylallyl pyrophosphate
Delta 3 isopentonyl pyrophosphate

10C = geranyl = fesyl

15 = farnesyl

30 = Squalene

17
Q

Which step in stage 3 of cholesterol synthesis requires NADPH?

A

Squalene synthase

15C + 15C

18
Q

Cholesterol synthesis
4 main steps

A
  1. Mevalonate synthesis from acetyl CoA (1 NADPH) (RLS)
  2. Activated isoprene synthesis from Mevalonate (3ATP)
  3. Squalene synthesis from 6x activated isoprenes (1 NADPH)
  4. Squalene cylcization and modification (1 NADPH)
19
Q

Where are cholesteryl esters formed and by what enzyme?

A

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

20
Q

LDL

A

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

21
Q

Short term regulation of cholesterol metabolism

A

Insulin = dephlsphorylates HMGcoA carboxylase = activated
Glucagon = deactivates
AMPK = low ATP = deactivates

22
Q

Longer term regulation of cholesterol synthesis

A

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

23
Q

Other isopentonyl derivatives
= isoprenoids

A

Vitamin KEA
Rubber
Plant hormones
Phyto chain of Chlorophyll

24
Q

Protein prenylation

A

Proteins anchored to surfaces = biological activity

25
Q

SREBPs additional proteins

A

SCAP = like scab = hanging on to skin

Insig = insulin signifant = in sick = in ER

26
Q

HMG CoA reductase requires how many NADPH?

A

2