Michigan State University

1. Orotate synthesis
2. Orotate synthesis / Orotidylate formation
3. UMP formation (decarboxylation)
4. UTP (phosphorylation)
5. CTP (amination) Cytosine tri-phosphate
6. TTP and dCTP (reduction)

Additional info:
- Control of pyrimidine synthesis

Pyrimidine De Novo Pathway

- Comprised of carbamoyl phosphate and aspartate
- From carbamoyl phosphate synthetase II
- Catalyzes the rate limiting step in pyrimidine de novo synthesis
- Cytosolic enzyme that synthesizes carbamoyl phosphate
- Synthesis of carbamoyl phosphate
> 1. Bicarbonate uses ATP to become carboxyphosphate
Phosphorylation
> 2. Carboxyphosphate + NH3 -> Carbamic acid
Amination
> 3. Carbamic acid + ATP -> ADP + Carbamoyl phosphate
Phosphorylation

- This enzyme works by channeling
- Diminishes loss of substrate by diffusion and non-productive reactions (hydrolysis)
- There’s one in the urea cycle too
- Gln + CO2 + 2 ATP + H2O -> carbamoyl phosphate + Glu + 2 ADP + Pi


Orotate Synthesis

- Carbamoyl phosphate and aspartate combine to make carbamoyl aspartate and Pi

- Carbamoyl aspartate becomes dihydroorotate

- Dihydroorotate and NAD+ -> NADH + H+ + Orotate

- Attachment of orotate to PRPP

- - Replaces pyrophosphate

- Reaction is driven forward through hydrolysis of PPi PPi leaving group

- Enzyme: Pyrimidine phosphoribosyltransferase

- Product: Orotidylate (OMP)

Orotate synthesis / Orotidylate formation

- UMP formation (decarboxylation)
- The decarboxylation of Orotidylate yields uracil triphosphate precursor, uridylate (UMP)
- H+ -> CO2 also


UMP Formation (decarboxylation)

- Making CTP from UTP
- Adding an amino group
- As with the formation of carbamic acid
- - The first amino group comes from glutamine
- - =O is first phosphorylated then aminated, with loss of Pi


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