Met 2: Purine/Pyrimidine Flashcards
Compare the structure of Purines and Pyrimidines
Classify the nitrogenous bases.
- Purines: two rings, Adenine, Guanine
- Pyrimidines: one ring, cytosine, thymine (only DNA), uracil (only RNA)
______ bases are built onto the ribose sugar
_______ bases are built by making the base first and then attaching ribose later
Purine bases are built onto the ribose sugar
Pyrimidine bases are built by making the base first and then attaching ribose later
AMP and GMP are produced from ____
AMP and GMP are produced from IMP
Name the intermediates leading up to AMP and GMP
G6P -> Ribose 5 Phosphate -> 5 PRPP -> IMP ->
AMP and GMP
Describe the first step in purine synthesis
Glucose 6 phosphate converted to ribose 5 phosphate in HMP shunt (by G6P dehydrogenase)
Describe the second step of purine synthesis.
What is the enzyme and its inputs
Ribose 5 phosphate converted to 5 PRPP
by PRPP synthase
Requires ATP and Mg
Describe the third step of purine synthesis.
What is the enzyme?
What are its inputs? (5)
5 PRPP converted to IMP
by G PRPP amidotransferase
Glycine, Glutamine, Aspartate donate NH3
THF, CO2 donate carbon
Describe regulation of IMP conversion into AMP and GMP (2)
- Increased concentration of one nucleoside upregulates production of the other b/c
- Conversion of IMP into GMP requires ATP
- Conversion of IMP into AMP requires GTP
- Both pathways also have negative feedback (GMP and AMP inhibit their own production)
What two main enzymes are regulated in purine synthesis?
PRPP Synthase
Glutamine PRPP Amidotransferase
How are PRPP synthase and Glutamine PRPP amidotransferase regulated?
- PRPP synthase and glutamine PRPP amidotransferase are both regulated using negative feedback
- They are inhibited by IMP, AMP, GMP (downstream products)
What enzyme in pyrimidine synthesis gets regulated?
What are its two inputs?
Name 2 allosteric regulators
Carbamoyl phosphate synthase 2
Inputs are CO2 and Glutamine
Activated by ATP, inhibited by UTP
Name the 6 intermediates in pyrimidine synthesis
Glutamine + CO2 -> Carbamoyl phosphate -> orotic acid -> UMP -> UTP -> CTP
What 3 substances provide the carbons for pyrimidine synthesis?
Glutamine, CO2, Aspartate
- Glutamine and CO2 are inputs for CPS2
- Aspartate comes in later
What enzyme converts UTP into CTP?
What are its inputs?
CTP Synthase
Inputs: UTP and ATP
CPS I and CPS II are found in which pathways?
In what location?
CPS I: Part of urea cycle, in mitochondria
CPS II: Part of pyrimidine synthesis, in cytosol
Compare the allosteric regulators of CPS I and CPS II
CPS I: activated by N acetyl glu
CPS II: activated by ATP, inhibited by UTP
What enzyme converts RNA nucleotides into DNA nucleotides?
Ribonucleotide reductase
Describe the regulation of ribonucleotide reductase
- Activity site is inhibited by dATP (product) and activated by ATP (precursor)
- Substrate specificity site determines which deoxynucleotide gets made
How is dTMP made?
Name one cofactor
dTMP (thymidine DNA nucleotide) is made from dUMP by thymidilate synthase
THF needed to donate methyl group
What are the 4 intermediates in purine breakdown?
Adenosine -> Inosine -> Hypoxanthine -> Uric Acid
Describe the enzymes involved in purine breakdown
- Adenosine deaminase needed to convert adenosine into inosine
- Xanthine oxidase needed to convert hypoxanthine into uric acid
What is the product of pyrimidine breakdown?
Pyrimidine breakdown products are inputs for TCA cycle (acetyl coA, malonyl coA, succinyl coA)
Describe the purpose of the purine salvage pathway
- Purines are normally built onto ribose rings
- Purine salvage pathway allows us to take purine bases that are already made and put them back onto rings
What enzyme is needed for purine salvage?
What does it do and what are its inputs?
by Hypoxanthine Guanine Phosphoribosyl Transferase (HGPRT)
Converts adenine, guanine into AMP, GMP
Requires PRPP
How does adenosine deaminase deficiency cause SCID?
- Without adenosine deaminase, can’t degrade adenosine into inosine
- dATP builds up
- This inhibits ribonucleotide reductase (produces DNA nucleotides from RNA nucleotides)
- Damages cell proliferation