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What do you need deoxy version of nucleotides for?
You need the deoxy version of nucleotides in order to make DNA
What is the name of the enzyme used to make the deoxy version of purines and pyrimidines
The enzyme is called Ribonucleotide reductase
What is the name of the reducing agent used to make deoxy ribose?
The name of the reducing agent is Thioredoxin
what is dNDP?
deoxyNucleotide Diphosphate
What is thioredoxin?
This is a protein with two cysteine groups that form a disulfide bond. It is used as a reducing agent. It is used in the reaction to made the deoxy version of nucleotides.
What is the reducing agent used to change thioredoxin back to its reduced form?
NADPH
What is the name of the enzyme that changes thioredoxin back to its reduced form?
Thioredoxin reductase
What is the enzyme name that changes thioredoxin to its oxidized form?
ribonucleotide reductase
What does the pathway for the reduction of ribose to deoxyribose look like?
What does GMP stand for?  Spell it.
Guanosine Monophosphate
What does AMP stand for?  spell it.
Adenosine Monophosphate
What does IMP stand for?  Spell it.
Inosine Monophosphate
What is the name of the nucleoside and the nitrogenous base that compose GMP?
The nucleoside is Guanosine.
 
The nucleic acid base is Guanine.
Is GMP a purine or a pyrimidine?
Purine
How does AMP change to IMP
By losing NH4+
Thioredoxin uses a type of metal.
 
What is that metal and what is this type of protein catagory?
The metal is Selenium.
 
This is a seleno protein.
What enzyme converts AMP to IMP?
 
Write the equation.
AMP deaminase.
 
AMP (AMP deaminase) ==> IMP + NH4+
In nucleotide metabolism, what does GMP become?   Name the enzyme that does this.
 
Write the equation.
 
What type of reaction is this?
Guanosine
 
GMP + H2O (5'-nucleotidase) ==> Guanosine + Pi
 
This is a hydrolysis reaction.
In nucleotide metabolism, what does IMP become?
 
Name the enzyme that does this.   Write the equation.
 
What type of reaction is this?
Inosine
 
IMP + H2O (5'-nucleotidase) ==> Inosine + Pi
 
This is a hydrolysis reaction.
In nucleotide metabolism, what does guanosine become?
 
What is the name of the enzyme that does this?
 
Write the equation.
Guanine
 
purine nucleoside phosphorylase
 
Guanosine + Pi (purine nucleoside phosphorylase) ==> Guanine + ribose 1-phosphate
In nucleotide metabolism, what does Inosine become?
 
What is the name of the enzyme that does this?
 
Write the equation.
Hypoxanthine
 
purine nucleoside phosphorylase
 
Inosine + Pi (purine nucleoside phosphorylase) ==> Hypoxanthine + ribose 1-phosphate
What does ribose 1-phosphate become?
 
What enzyme is used to do this transformation?
ribose 5-phosphate
 
Phosphoribomutase
What does Ribose 5-phosphate become?
 
Write the equation.
PRPP
 
ribose 5-phosphate + ATP ==> PRPP + AMP
What is the name of the enzyme that changes hypoxanthine to xanthine?
 
What else does this enzyme do?
Xanthine oxidase
 
It also converts Xanthine to Uric acid
What is the oxidizing agent that Xanthine oxidase uses?
 
What is given off after the reaction?
O2


H2O2
What is the name of the drug that inhibits Xanthine oxidase?
Allopurinol
What are the cofactors in the active site of Xanthine oxidase?
 
What is the last step of the electron transport?

  • Mo+6 ==> Mo+4

  • The Irons of Iron sulfur centers
    Fe+3 ==> Fe+2

  • FAD ==> FAD2H


 
The last step is that the 2H goes to the O2 and H2O2 comes out
What type of protein is an enzyme that has FAD or FMN in their active sites?
A Flavo protein
What happens when you have high concentrations of Uric Acid?

  • The Uric Acid begins to crystalize and it becomes gout in the joint spaces of the body.  This causes incredible inflammation, pain, swelling, and joint destruction.

  • Some kidney stones are Uric Acid stones.

  • The Uric Acid will increases blood pressure by interfering with vaso dilation.

Draw the purine nucleotide degradation pathway / formation of uric acid/urate.
What are the two enzymes of the purine salvage pathways?

  • adenine phosphoribosyltransferase (APRT)

  • hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

Draw out the Purine Salvage Pathway
READ ABOUT GOUT

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Describe or Draw the gout pathways
Is gout caused by Purine or Pyrimidine?
Purine
How does Colchicine work?
Deal with the acute inflammation. Works by inhibiting the formation of microtubules inside white blood cells (neutrophils).
 

  • This prevents the neutrophils from migrating normally.

  • A lot of the pain in a gout attack is caused by neutrophils phagocytizing uric acid crystals and then not being able to dissolve/break them down.  By inhibiting the microtubules you are also preventing the neutrophils from phagocytizing the uric acid crystals.

  • You are also preventing the neutrophils from secreting chemical messengers that would draw other white blood cells to the area.

How does Allopurinol work?
It resembles purine. This resemblance to the normal substrate of the xanthine oxidase, it becomes a competitive inhibitor.

What are the class of drugs that help increase the excretion of uric acid in the urine?
Uricosuric drugs
What is Lesch-Nyhan syndrome?   Why are these patients almost always male?
This is a problem with the HGPRT reaction. There is one copy of this gene on the X chromosome. This syndrome is caused by a mutation in that gene that totally wipes out the activity of the HGPRT.

Because this is a X linked recessive condition.
Why does someone with even a partial deficiency of HGPRT have an increased risk of gout.
They have a high risk of gout because they are eliminating their purines instead of recycling them.
What is the consequence of an adenosine deaminase deficiency?
This causes a very sever combine immuno deficiency.  (Before there was treament for this, these were the bubble boys)
What enzyme is needed to take a nucleoside to a free base?
purine nucleoside phosphorylase
 
What consequences does Lesh-Nyan syndrome have?

  • High risk of Gout

  • Sever mental retardation

  • Self mutilation

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