Nucleotide Metabolism Flashcards
What are nucleotides
phosphate esters of nucleosides
Nucleoside
Base + sugar
Nucleotide
nucleoside becomes a nucleotide when a phosphate group is added
Deoxynucleotides lack a _____
OH group, making it more stable
The sugar is connected to a base via a ________ bond
glycosidic
Purines
2 rings Adenine Guanine Xanthine Hypoxanthine
Pyrimidine
1 rings
Adenine is a _____
base
What happens when you add a sugar (deoxyribose) to adenine?
Adenosine
-ine means a sugar has been added and you have a NUCLEOSIDE
Adding a phosphate group to adenosine?
adenosine-mono-phosphate (AMP)
Nucleosides and nucleotides have several roles
they can be
- cofactors
- regulatory roles by serving as signaling molecules
- stabilize
Where do carbons from purines and pyrimidines come from?
we can get them all over the place.
In purine nucleotide synthesis, we begin with the synthesis of the ______ first, and then _______
PURINE (A, G, Xan, HypoXan) Synthesis, we begin with the synthesis of the SUGAR first
And then the RING formation
What are the 4 steps in purine ring formation
- Activate Ribose-5-phosphate
- Convert PRPP–> PRA
- Make an IMP Ring
- Create adenosine and guanosine nucleoTides
the ribose-5-phosphate that we begin with in purine ring formation comes from
PPP
Step 1 of Purine Ring formation
- We are going to convert R5P to its activated form PRPP via [PRPP synthetase]
R5P–> PRPP via [PRPP synthetase]
ATP is used
R5P to PRPP is allosterically regulated
(+) Pi levels
-) by purine nucleotides (why make more if you already have some
Step 2 of Purine Ring Formation
PRPP–> PRA via [glutamine:PRPP amidotransferase)
This is the commital step! In this step, we substituted a pyrophosphate with an amino (NH3) group from glutamine.
What does PRA stand for
phosphoribosomal amine
Allosteric regulation when PRPP–> PRA
(+) PRPP
-) purine nucleotides like (GMP, AMP, IMP
Step 3
Create Inosine monophosphate (IMP) ring
PRA enters a 9 step reaction to create a ring.
We started with a sugar and build a ring on top.
What is important to note about one of the 9 steps that occur in creating the ring.
When creating the ring, 2 of the carbons that are added will come from THF (tetrahydrofolate).
In summary: what does methotrexate do?
It prevents the formation of purine-nucleotide ring formation
Doing this will inhibit DNA replication.
Methotrexate
Methotrexate interferes with the IMP ring formation in purine nucleotide formation.
It will attack dihydrofolate reductase, to prevent the conversion of folate to THF (which as we said, donates 2 carbons to the ring formation).
Thus, it will disrupt ring formation
What type of inhibitor is methotrexate?
Methotrexate is a competitive inhibitor that binds to many things that use folate.
It binds to DHF reductase more tightly!
What enzyme does methotrexate competitively inhibit?
Dihydrofolate reducatase.
Folic acid and ______ are very similar in structure
methotrexate
Step 4 of Purine Symthesis
Summary
We use the IMP to make AMP and GMP
_____ is the metabolic branch for the synthesis of AMP and GMP
IMP
How do we get from IMP to AMP?
2 reactions
- [adenylosuccinate synthetase] converts IMP to adenylosuccinate monophosphate
- Adenylosuccinase causes fumarate leaves and AMP is created!
How to we get from IMP to GMP?
- IMP–> Xanthosine monophosphate (XMP) via IMP dehydrogenase
- XMP–> GMP via GMP synthetase
Regulation in this pathway is cool. Why?
Because the products will exert regulation on themselves to promote the synthesis of the one another.
For example, if we have too much AMP, this will stop the production via [adenylosuccinate synthetase] and promote the synthesis of GMP!
And vice versa.
High GMP will tell IMP DH to sto!
AMP synthesis is stimulated by the presence of ______
in the purine synthesis path
GTP
GMP synthesis is stimulated by the presence of _____
in the purine synthesis pathway
ATP
What are SULFA drugs?
Sulfa drugs are competitive inhibitors that block the enzyme that put PABA into folate.
Thus, they disrupt DNA replication in bacteria
Do SULFA drugs affect humans?
No, because we get folate from our diet.