Cholesterol Biosynthesis and Sterol Derivatives Flashcards

1
Q

Describe Cholesterol structure

A

Hydrophobic with four fused hydrocarbon rings (called the steroid nucleus)

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

What are sterols?

A

Sterols are steroids with eight to ten carbon atoms in the side chain at C-17 and a hydroxyl group at C-3.

Cholesterol is the major sterol in animal tissues. Plant sterols are poorly absorbed by humans

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

What are Cholesteryl esters (CE)?

A

Most plasma cholesterol is in an esterified form causing it to be even more hydrophobic than free cholesterol. These do not work well in membranes and are only present in low levels in most cells

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

What do acetate and NADPH do for cholesterol synthesis?

A

Acetate provides the carbon atoms in cholesterol and NADPH provides the reducing equivalents

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

How is the pathway for cholesterol synthesis driven? And where does it occur?

A

Pathway is driven by hydrolysis of the high-energy thioester bond of acetyl CoA and there terminal phosphate bond of ATP.

Synthesis occurs in the cytoplasm with enzymes in both the cytosol and at the membrane of the E.R.

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

How do you synthesize HMG-CoA?

A

2 Acetyl CoA –> Acetoacetyl CoA –> HMG-CoA

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

What does HMG-CoA reductase do? What inhibits it?

A

HMG-CoA reductase converts HMG-CoA to Mevalonic Acid.

Cholesterol will inhibit it

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

Describe process of Mevalonic Acid to FPP

A

See powerpoint and write out

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

What is squalene?

A

When two molecules of farnesyl pyrophosphate (FPP) combine and release pyrophosphate and are reduced they form squalene

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

What causes the conversion of squalene to lanosterol?

A

The hydroxylation of squalene will trigger the cyclization of the structure to lanosterol

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

What is Smith-Lemli-Opitz Syndrome (SLOS)?

A

A common autosomal recessive disorder of cholesterol biosynthesis, caused by a partial deficiency in 7-dehydrocholesterol reductase which is an enzyme that is involved in converting 7-dehydrocholesterol to cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the first precursor to sterol? What is the last precursor to sterol?

A

Lanosterol is the first precursor

7-dehydrocholesterol is the last precursor sterol en route to cholesterol

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

What does SREBP2 do? What happens when you have low or high cholesterol?

A

When SREBP2 binds to SRE it will increase expression of HMG-CoA reductase.

When you have low cholesterol, SREBP2 activity will increase.
When you have high cholesterol, SREBP2 activity is reduced

SREBP2 activation also activates the LDLR gene

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

What does Dihydrolanosterol or 27 hydroxycholesterol do?

A

It affects the stability of the HMG-CoA reductase protein and leads to decreased stability (and therefore increased degradation)

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

Describe when HMG-CoA reductase is phosphorylated and dephosphorylated

A

ACTIVE: Dephosphorylated
INACTIVE: Phosphorylated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do hormones regulate HMG-CoA reductase?

A

INSULIN: increases expression of HMGR
Glucagon: Decreases expression of HMGR

17
Q

What drugs inhibit HMGR?

A

Statin drugs like simvastatin, lovastatin, and mevastatin. They are competitive inhibitors of HMGR

18
Q

What are coprostanol and cholestanol?

A

They are reduced derivatives of cholesterol. Together with cholesterol, these compounds make up the bulk of neural fecal sterols

19
Q

What happens to patients who lack functional LDLR receptors (familial hypercholesterolemia)?

A

They cannot catabolize LDL in their plasma, their LDL levels are several times higher than the normal values

20
Q

What does ACAT do?

A

Converts Cholesterol to Cholesterol esters. Prevents accumulation of cholesterol in cell membranes