Blomquist Flashcards Preview

Block 3; Week 2 > Blomquist > Flashcards

Flashcards in Blomquist Deck (38)
Loading flashcards...

What is the usual function of cholesterol?

used in the membrane
precursor to bile salts & acids
precursor to hormones
precursor to vitamin D


Which hormones is cholesterol a precursor for?

progesterone, estrogen, testosterone, cortisol, aldosterone


T/F Gall stones can be almost all cholesterol.



Which drug helps in the treatment of cholesterol?



Where is most of the cholesterol found in the human body? What effect does it have there?

in membranes!
The OH group interacts w/ surface (hydrophilic)
the body of the cholesterol is planar & rigid & is in the hydrophobic portion of the membrane
**it makes the membrane less fluid & more rigid


What is an example of a membrane that has a lot of cholesterol? What is an example of a membrane that doesn't have very much cholesterol?

Lots of Cholesterol: myelin sheath membrane (used for protection-->want rigidity)
Not much cholesterol: inner mitochondrial membrane


How many rings does cholesterol have? How many carbons? Where is its OH group situated?

27 carbons
4 rings
OH @ Carbon 3


Aside from 4 rings & 1 OH group...what are other features of the cholesterol molecule?

a few methyl groups
an 8 carbon side chain
a double bond


Is cholesterol hydrophobic?

It is also planar...
b/c of its hydrophobicity lipoproteins must carry it in blood.


What's the relationship b/w cholesterol & bile acids?

There is a LOT of cholesterol in bile acids. So much so that sometimes it precipitates out as gallstones.


Compared to glucose in the blood...what are the ideal levels of cholesterol in the blood?

about 2X that of glucose
around 200...ideally less


What form does most cholesterol take in the blood?

that of a cholesterol ester


There are 2 ways to make a cholesterol ester. What is the way including ACAT?

Cholesterol + Fatty Acyl-CoA
Enzyme: ACAT: acyl CoA cholesterol acyl transferase
= Cholesterol Ester


There are 2 ways to make a cholesterol ester. What is the way including LCAT?

Cholesterol + Lecithin
Enzyme: LCAT: lecithin cholesterol acyl transferase


So...we know that cholesterol can be made from acetyl CoA. What are our 2 major sources of Acetyl CoA?

Fatty Acids--LIPIDS


What do you need a lot of to form either cholesterol or fatty acids?



So...we have a ton of acetyl coA trapped in the mitochondrial matrix & we need it in the cytoplasm for cholesterol biosynthesis. How do we move it?

Acetyl CoA + OAA-->Citrate via citrate synthase.
this goes thru SLC25A1 on the inner mitochondrial membrane. It diffuses thru the outer mitochondrial membrane.
ATP-citrate lyase breaks citrate into OAA & Acetyl CoA.
Now, the acetyl CoA is in the cytoplasm & ready to go. For more details look @ the figure.


What are the basic steps from acetyl CoA to cholesterol?

Acetyl CoA


What is the key regulatory step in cholesterol synthesis? What enzyme is involved?

Acetyl CoA-->Mevalonate
Enzyme: HMG-CoA Reductase


How do you make HMG-CoA?

2 Acetyl CoA-->Acetoacetyl CoA
Acetoacetyl CoA + H2O -->HMG CoA
This last step uses the enzyme: HMG CoA Synthase


If the HMG CoA is made in the cytosol...what is the result?

It goes on to make cholesterol.


If the HMG CoA is made in the mitochondrial matrix...what is the result?

it goes on to make ketone bodies.


Once again, what is the key regulated step in cholesterol synthesis?

HMG CoA + 2 NADPH -->Mevalonate
Enzyme: HMG CoA reductase
Note: 2 NADPH per 1 mevalonate


Where is the HMG CoA reductase found?

It is an ER bound enzyme.


What are the ways in which HMG CoA reductase is regulated? What are the 2 most important ways?

1. feedback inhibition
2. phosphorylation/dephosphorylation
Most important:
3. Control of gene expression
4. Rate of enzyme degradation


Why is it that after changing diet & exercise...many people don't see a change in their cholesterol levels?

b/c of feedback inhibition
the more cholesterol-->the less HMG CoA reductase is active
the less cholesterol-->the more HMG CoA reductase is active
If you reduce cholesterol intake, maybe the enzyme will just boost its activity. This is why statins have been so helpful.


Which form of HMG CoA Reductase is active.
The phosphorylated form or the dephosphorylated form?

the dephosphorylated form is active


Explain a little about the control of gene expression as a way of regulating HMG CoA reductase.

SREBP when not stuck in the ER membrane binds to target gene in the nucleus & increases the production of HMG CoA reductase. This happens in response to low sterol levels.
SREBP: sterol receptor element binding protein


How do statins work?

One of the groups on the statins competes with HMG CoA for the active site of HMG CoA Reductase...
This reduces the cholesterol that ends up being made


As a result of taking sorta shut down a long pathway that could contribute to making other things aside form cholesterol...this doesn't seems to be a problem BUT what products might you have less of as a result of taking statins?

prenylated proteins
heme a
vitamin D
bile salts