Nucleotides Pyr Flashcards
Pyrimidine Ingredients
Gln, Asp, CO2, ATP, PRPP, FAD
Pyrimidine Synth step 1
Make carbomyl phosphate
Gln, CO2, ATP used
Enz = CPS 2 (same as CPS 1 but not in mito)
Rqrs PRPP inhib by UTP
Pyrimidine Synth step 2-4
Make orotic acid
From addition of Asp to Carbomyl phosphate, makes body of pyr
Pyrimidine Synth step 5-6
Finish body
Orotate binds PRPP to OMP to UMP
enz = UMP synthase
Pyrimidine Synth step 7
UMP to UDP
rqrs ATP, UDP to UTP or dUDP therefore number of P added determines UDP outcome
Pyrimidine Synth step 8a
UDP to CTP/dCTP
UDP to UTP to CTP (rqrs Gln)
CTP minus P (ribonucleotide reductase) to dCTP
Pyrimidine Synth step 8b
UDP to dUDP
enz = ribonucleotide reductase which reduces ribose sugar and is used for all DNA
act by ribonucleotides and inhib by deoxyribonucleotides (enough DNA)
Rqrs Thioredoxin and NADPH; irreversible
Pyrimidine Synth step 8c
dTDP
UDP to dUDP (ribonuc reductase) to dUTP (add P) to dUMP (minus PP) to dTMP (add CH3, via thymidylate synthase, rqrs THF-Me)
Pyrimidine Degrade
Degraded to soluble molecules which are converted to acetyl CoA, Succinyl CoA
No salvage pathway
Orotic Aciduria
Mut in subunits of UMP synthase; Orotate phosphoribosyl transferase or OMP decarboxylase
leads to poor growth, megoblastic anemia, orotic aciduria
Treatment is admin of uridine to improve anemia and decrease excretion of orotic acid as it inhibs CPS2
Xeroderma Pigmentosa
AR
Pyr dimerization due to UV dmg, no nucleotide excision repair
Methylated Cytosines
When cytosines are methylated by SAM, they can spont deaminate to Thymine
Screws up DNA sequence
5-Fluorouracil
Prevents dUMP methylation therefore inhib thymine buildup