Chapter 23

What is the precursor for bile acid?

In normal quantities, cholesterol  have adverse impacts on health

Cholesterol can be synthesized from   synthesis, in other words, they can be made  

  is the precursor for making cholesterol

In the formation of cholesterol,   is turned into  , the to  , then into  , and cyclized into  

 is the key step in cholesterol synthesis

Regulation in cholesterol synthesis occurs at the  and also at the   (i.e.  / )

 inhibit the HMG CoA reductase

Statins are   (type of inhibitor competetive, non-competetive, uncompetetive)

Formic acid

Acetic acid

Propionic acid

Butyric acid

Caproic acid

Caprylic acid

Capric acid

Lauric acid

Myristic acid

Pamitic acid

Stearic acid

Pamitoleic

Oleic acid

Linoleic acid. What isimportant about it?

Linolenic acid. What is important about it?

Arachidonic acid

How many carbons does cholesterol have? How many ring?

Important structures of cholesterol

What is the most hydrophobic compound in biological systems?

If the -OH in cholesterol is replaced with a sulfur group, what is it's role?

Cholesterol can be esterified to form    or 

If the is isopropyl group is replaced with -COO-, what does it become?

What type of hormone does cholesterol form?

What type of vitamin does cholesterol serve as a precursor for?

Within the cell
membrane cholesterol
functions in  

Cholesterol plays a role in cell   and  

Cholesterol is essential
for the structure and
function of
invaginated   and 

Cholesterol is involved in
 endocytosis.

In atherosclerosis, there is an accumulation of   cholesterol and leads to the formation of a  . The macrophaes interact with the plauge and bcomes  .

In de denvo synthesis, two molecules of   combine to form   using   enzyme. This is the first step and happens in the  .

In the second step of the denovo synthesis,   is converted into   using   and  .

In the third step of de novo synthesis, HMG CoA is converted into  using  and  

HMG COA reducatse is an  

HMG COA Reductase is   by statins

HMGR has   (888 amino acids) and (835 aminio acids)

HMG CoA Reductase (HMGCR) is
derived from the HMGCR gene that is
located on chromosome 

HMG CoA Reductase is made of   that generate   alternatively spliced mRNA that encode its  

Mevalonate is converted to IPP using  ,  , and   is converted.

IPP gets isomerized into to form  

When IPP is added to  , it forms  , which then condenses with another   to form  

Squalene is acitivated by oxygen to form   and then forms   which is the first  . Lanosterol then become cholesterol.

FPP can also become   (  +  )

Dolichol
(used in the synthesis of  ), coenzyme
Q (of the  ), or the side chain of 

Draw general schematic for squalene synthase

From Acetyl CoA it takes  
steps to Lanosterol

From Lanosterol to
Cholesterol in   steps

Cholesterol de novo Synthesis:
Occurs Mainly in 
Also some in  ,
 and
 

If squalene synthesis is inhibited, will be adveresely impacted

High Cholesterol inhibits  (  inhibition).

High Cholesterol activates  which  
HMG‐CoA reductase and it.

High Cholesterol leads to  
degradation of  

We did not get into the gene level controls, but do know that it is done by  

Ubiquinone is part of the  

Ubiquinone - If it is   produced (from de novo) pathway properly, it can then cause
 .

Heme A is a   for
cytochrome aa
3 (also
known as
 ) of
 .

Deficiency in   (due to gene
mutations) results in the disorder
called Smith‐Lemli‐ Optiz Syndrome
(SLOS). SLOS is characterized by increased
levels of  and
reduced levels (15% to 27% of normal)
of  resulting in multiple
 and
 

Side effects of   include to Muscle Weakness, Muscle
Pain, Myopathy (Actual
Damage of Muscle Tissue), and Peripheral Neuropathy
(burning Pain)

  may help reduce low-density lipoprotein (LDL) cholesterol and total cholesterol levels

New drugs act on the   instead of HMG CoA Reducatse (statins)

Squalene synthase
inhibitors include as  ,  
(SQS Inhibitor), and  
(a natural
product Inhibitor
from Fungi)

High HDL is a risk factor for  

Bile Acids and Bile
Salts are  

Bile acids are   in
that the   are hydrophilic
pointing downward and the  
groups are hydrophobic

Cholesterol is converted to bile acid by 

Bile contains liquid mixture of  
and  .

 (lecithin) and  (conjugated bile acids) are the most
important compounds.

Bile synthesized in  and stored in
 .

CCK stimulates the contraction of  to release  .

  conjugated onto cholesterol form bile salt

Bile salts are more amphipathic and therefore  

Seondary bile acids necessitate healthy intestinal  .   to   necessitates this.   (diol) to  necessitates this.

Bile acids/salts are transported back from  through
 and taken up by  

  in the blood ties up the bile acids.

Liver picks it up from blood, conjugates the bile acids into bile salts sends
it back thru bile duct in to  and stores them in the  .

Cholestyramine and Dietary Fiber binds bile acid/salts. This diverts more cholesterol in   and 

Cholelithiasis involves less   and
  in Gall bladder. More   in the bile
causes precipitation and forms  

  It results from cholesterol
deposits in corneal stroma. It is an indicator of
  or
 , in younger
individuals

 
No Clear Correlation with
Increased risk of
atherosclerosis

 :
Indication of Familial
Hypercholesterolemia