Lecture 4 Prep for Exam 1 Flashcards
In what form are triglycerides stored in our body?
esters and glycerol
The gallbladder is basically the _____ factory of the body
salt
How do you convert something that is very lipophilic (such as cholesterol in this case) and make it very amphiphilic (such as cholic acid in this case)…
you make it more polar
Amphiphiles are both polar and nonpolar…what do they help aid in?
They are emulsifying agents (detergents) that aid in the digestion of lipids
Where is the main factory of proteins?
the liver…
What is occuring in the liver?
primary bile acids synthesis…cholesterol being converted into CA or CDCA (via the enzyme CYP7A1
After the bile acids are made in the liver, where are they stored?
gallbladder!…these bile acids must be ready on demand once you have something of fatty material
How many 6-membered rings does the steroid structure have? How many 5 membered rings does it have?
3 “6-membered” rings and 1 “5-membered” ring
What structure is this?
steriod!
How do we make amphiphilic material from lipophilic cholesterol?
First the hydroxylase is put at the 7th position due to NADPH being reduced to NADP+, then two things can happen to either produce Cholic Acid or Chenodeoxycholic acid…
For Cholic Acid: the 12-alpha hydroxylase will help with attaching hydroxyl group at the 12th position, there will be a reduction of the double bond in the 6 membered ring, and there will be a side chain oxidation and cleavage
For Chenodeoxycholic acid: there will be a reduction of the double bond in the 6 membered ring and there will be a side chain oxidation and cleavage (just no 12th position -OH addition)
explain oxidation and reduction: (in terms of gain/loss of oxygen, gain/loss of hydrogen, gain/loss of electrons)
Which is more polar?
cholic acid
If you want the best emulsifying agent you want them to be:
a) very lipophilic and very hydrophilic
b) very lipophilic and very hydrophilic
a) very lipophilic and very hydrophilic
Someone gives you a drug and says they want you to make it more water-soluble…how would you do this?
more water soluble=more hydrophilic
I would then ask if it is an acid, if yes, then I will add a base
If it is a base, then I would add an acid
Altogether you are getting the ionized form which is the water soluble form! Excreted more easily
(more ionization=more charge=more polarity)
Can you use thioesters or esters for chemical reactions?
Use thioesters (are less stable) and you can easily modify them…they are weaker than esters
Which is the nucleophile in the equation?
the amine group
Where does the amine attack?
The amine will attack the carbon of the thioester group because it is more lipophilic and will transform easily to yield the acetyl choA product
Because of the thioester reaction with amine that we understand, what basically occurs in the reaction?
The CoA-SH is replaced by either Taurine or glycine…in the thioester reaction with amine essentially the S was replaced with the NH…in the case of Cholyl-CoA with addition of Taurine or Glycine to yield Taurocholic acid or glycocholic acid
What is the main message showing us from this reaction?
We cannot directly react an amine with a carboxylic acid
You must take the carboxylic acid and put the acid first, activate it with acetyl coA, and then react it with the amine
What is the pkA of the two acids?
about 5
What is the pH of the stomach? What is the pH of the first part of the small intestine (the duodenum)? What about the pH of the lower part of the small intestine?
pH of stomach= about 2
pH of duodenum= about 4
pH of the lower part of the small intestine= about 7.4/8
Are these molecules in their protonated or their unprotonated form?
If you want these molecules to have better water solubility..you want them to be…
CO-! ionized=better water solubility
Can we adjust the ionizability of these bile salts in order to make it more water soluble?
The answer is yes, because look at the pKa now of these primary bile acids…