Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

1. BIOC 1301 S2 > Cholesterol > Flashcards

Cholesterol Flashcards

1
Q

Describe the structure of cholesterol?

A 
27C molecule
4 ring steroid nucleus - 3 6C and 1 5C. Rings referred to as A,B,C,D. 
OH group on C3
Methyl groups at position 18 & 19
Hydrocarbon ‘tail’

Cholesterol is found mainly in animal cells – plants contain v small amounts
Bacteria cannot synthesise sterols

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the properties of cholesterol?

A

Rings give cholesterol a rigid planar structure
Molecule is amphipathic – polar OH group at one end, hydrophobic tail at the other

Cholesterol is essential for life: membranes, vitamin D, hormones and bile salts
BUT raised levels of circulating cholesterol are a major contributing factor to the development of cardiovascular disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Where can cholesterol be situated?

A

Membrane

Myelin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe cholesterol in the membrane?

A

Cholesterol sits between phospholipids in membrane

It is not evenly distributed throughout membranes
Atomic force microscopy shows this
Microdomains - ‘rafts’ can be seen which are thicker than surrounding lipid areas
Rafts involve: choleterol and GPI anchored proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe cholesterol in myelin?

A

It contains around 20% cholesterol with the brain being the most cholesterol-rich organ in the body
Myelin sheath surrounding neurons consists primarily of lipids and has a high cholesterol content
The cholesterol decreases the permeability to ions, and so increases the insulating effect of myelin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What can we produce from cholesterol?

A

Vitamin D synthesis
Steroid hormone synthesis
Bile synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How is vitamin D synthesised?

A

UV light alters the 7-dehydrocholesterol, before being hydrolysed into calcitrol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are steroid hormones used for? How can they be produced?

A

Sexual development and reproduction (progesterone, oestrogens, testosterone)
Homeostasis of Na+ and K+ ions ( aldosterone)
Responses to stress, infection etc (cortisol)

Synthetic reactions involve removal of hydrocarbon ‘tail’ and various hydroxylations
First step in the pathway is catalysed by Cytochrome P450 side chain cleavage (requiring NADPH and O2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What can you do with bile salts?

A

You can add amino acids to them - making them more amphipathic
By adding taurine or glycine to cholyl CoA we can form taurocholic acid and glycocholic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are some sources of cholesterol?

A

From the diet – eggs (yolk), liver, meat – i.e. mainly animal sources
Synthesis – in almost all tissues - mainly in the liver and intestine

Plant sterols/stanols (structurally closely related to cholesterol) inhibit cholesterol uptake from the gut

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the overview of cholesterol biosynthesis?

A
  1. Acetyl CoA to mevalonate (C6)
  2. Mevalonate to phosphorylated isoprene units (C5) (activation)
  3. Polymerise 6 isoprene units to form C30 chain
  4. Cyclisation to form ring structure
    First stage is most important as it controls rate of synthesis
    Occurs in cytosol and smooth endoplasmic reticulum
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is step 1 of biosynthesis of cholesterol?

A

Condensation of three acetyl CoA molecules in two separate reactions

Uses acetyl-CoA acetyltransferase, HGM-CoA synthase and HGM-CoA reductase (this is the control point)
This step can be inhibited by statins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is step 2 of biosythesis of cholesterol?

A
  1. Reduction of thioester to R-OH
  2. Phosphorylation of R-OH
  3. Phosphorylation to pyrophosphate (to maintain the solubility of these units)
  4. ATP dependent Decarboxylation
    Pyrophosphate groups keep molecules water-soluble
    = 6 Isoprene units

An ‘expensive’ process – 3 x ATP required for each IPP – 18 for one cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is step 3 of biosynthesis of cholesterol?

A

6 isoprenes -> squalene
In C=C isomerisation
4 isopentenyl pyrophosphates + 2 dimethylallyl pyrophosphates condense to produce C30 squalene

Different condensation reactions happen during this reaction:
Head-tail (involves a carbocation intermediate)
Head-tail
Head-head

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is step 4 of biosynthesis of cholesterol?

A 
Squalene -> cholesterol
1. oxidation
2. protonation of epoxide oxygen by enzyme.
3. Many methyl and hydride migrations
4. proton elimination (C9)
\+ 19 more steps = cholesterol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are some genetic diseases linked to cholesterol?

A 
Smith-Lemli-Opitz syndrome
They are missing one of the enzymes of cholesterol synthesis - leads to:
unusual facial features
fused/extra fingers
Poor growth
Mental retardation
17
Q

How can we control cholesterol?

A

High cholesterol levels = inhibit further synthesis
High energy levels = insulin increases and glucagon decreases

Short term control:
regulation of activity of HMG Co A (milliseconds) reductase by phosphorylation
feedback inhibition by high cholesterol levels
Longer term control:
regulation of amount of HMG CoA (mins-hours) reductase

18
Q

What is the mechanism of the cholesterol feedback loop to control HGM-CoA reductase?

A

When cholesterol levels in the cell are high, the SREBP-SCAP complex is in the endoplasmic reticulum
When cholesterol levels are low, SCAP escorts SREBP to the Golgi
SREBP is proteolysed releasing its N-terminal.
The N-terminal domain enters the nucleus and binds (bHLH) to the gene’s SRE, inducing transcription

19
Q

What is the conditon with high levels of cholesterol? What can we do to prevent high cholesterol?

A

Hypercholesterolemia

Take statins as they competitively inhibit HMG-CoA reductase
They bind to the enzyme with a ~nanomolar KI (very low)
The enzyme changes conformation to accommodate the large hydrophobic groups of the statins

20
Q

What diseases can be acquired from high cholesterol?

A

Atherosclerosis
This is caused by the build-up of lipids in the walls of blood vessels
A plaque then forms containing LDL cholesterol, and if it ruptures, a blood clot can form leading to a heart attack or stroke after feeling angina (pain in the chest)

21
Q

What factors can affect levels of serum cholesterol?

A

High cholesterol level in cells suppresses LDL receptor synthesis and more LDL remains in circulation
Deficiency in LDL receptors = familial hypercholesterolemia (FH) = risk of atherosclerosis

1. BIOC 1301 S2 (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions