Week 3 - Nucleotide Metabolism Flashcards
What are purine bases?
Adenine (A), Guanine (G)
What are pyrimidine bases?
Cytocine (C), Thymine (T)
What is structure of a nucleotide?
Pic.. Always leaves free hydroxyl group on 3’ end.

What are other bases and nucleosides?

What are nucleotide functions?
DNA RNA
Handles for enzyme cofactors
Energizing Substrates
Second Messagers
Allosteric Activators
Nucleotide ‘Handles’ for enzyme cofactors:
CoASH
NAD+
FAD
Adenosylcobalamin
Nucleotide Energizing Substrates
UDP-glucose
CDP-choline
Nucleotide Second Messangers
cAMP
Nucleotide Allosteric activators
AMP
ADP
ATP
Initial steps for Nucleotide synthesis:
Different for purines and pyridamines.
Both use same substrate which is synthesized from glucose in the pentose phosphate pathway to make Ribose 5-phosphste.
R5P is then phosphorylated to 5 Phosphoribosyl 1-pyrophosphate (PRPP) by PRPP synthase and ATP
From there purines and pyrimadines can be synthesized
What is common substrate for both purines and pyrimidines? Draw the reaction. What is it inhibited by?
PRPP This is key regulatory step for nucleotide synthesis.
Inhibited by GDP and ADP

What is enzyme to turn Ribose - 5-phosphate into PRPP? What energy does it use? What inhibits it?
PRPP synthetase ATP to ADP GDP and ADP
Purine Metabolism vs Pyridamine Metabolism
Puring starts with PRPP, builds it up from there..
Pyrimadine - base is assembled THEN tranferred onto PRPP…
What are the first two steps in purine metablolism from PRPP? Where is the carbon and nitrogen from? Where does the energy come from?
The first committed step in purine synthesis is the transfer of an amine from glutamine by the glutamine phosphoribosyl aminotransferase with the addition of water
The second step is the addition of glycine to make glycinamide ribosyl 5-phosphate (powered by ATP).

In order to form IMP in purine synthesis, where is the carbon and nitrogen from?
Carbon and nitrogen are added from tetrahydrofolate, carbon dioxide, glutamine and aspartate to form inosine monophosphate (IMP).
What is IMP? What is it turned into?
Inosine Monophosphate. It is the first monophosphate formed in purine synthesis. It can be turned into AMP and GMP which can be further turned into ADP, ATP, GDP, GTP (for RNA synthesis) and the dexoy ADP, dATP, dGDP, and dGTP (for DNA synthesis)

Reaction from IMP to AMP.
Similar to the amine transfer in the Urea Cycle…
Aspartate bonds to IMP to make adenylosuccinate, then fumarate is cleaved to to make AMP
GTP provides the energy in the first step - not ATP*

Reaction from IMP to GMP
To form guanosine monophosphate, IMP is first oxidized to xanthine monophosphate. Then an amine group is transferred from glutamine, using ATP hydrolysis to power the reaction

How to get ribos sugars to deoxy ribose sugars?
Adenosine monophosphate and guanosine monophosphate are then phosphorylated to diphosphates.
ADP and GDP can then be phosphorylated again and . . .
hydrolyzed for energy or enzyme regulation incorporated into RNA
Or. . .
The ribose sugar of ADP and GDP can be reduced to make dADP and dGDP.
Draw Reaction of NDP to dNDP. What is the enzyme?
2 carbon on the ribose sugar of ADP and GDP (or UDP or CDP) can be reduced to make dADP and dGDP
Reducing factor is NADPH* Depends on this.
The NADPH and ribose sugar comes from the pentose phosphate pathway
Thioredoxin reductase and ribonucleotide reductase are the enzymes

Takes a lot of energy to make nucleotides. How much energy can come out of their degradation?
Not much compared to what it takes to make them.
Purine salvage: Cells expend a lot of energy to make nucleotides. To conserve this energy, there are different pathways to recycle nucleosides and bases in the cell
What enzyme is defective in SCID?
An inherited deficiency in adenosine deaminase causes severe cobined immunodeficiency. Purine synthesis
AMP deaminase (only muscle issues if deficient) this is different then adenosine deaminase which has system wide effects if defective… Look at Purine Salvage chart.
What enzyme is defective in CID?
An inherited deficiency in purine nucleoside phosphorylase (PNP) causes combined immunodeficiency. Purine synthesis
What enzyme is defective in Lesch-Nylan Syndrome?
An inherited deficiency in hypoxanthine-guanine phosphoribosyltransferase causes. Purine synthesis




