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

- 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


CTP (amination) (Cytosine triphosphate)

TTP and dCTP (reduction)

In the pyrimidine de novo synthesis pathway, the decarboxylation of orotidylate (OMP) yields uridine monophosphate (UMP) and carbon dioxide (CO2). UMP, also known as uridylate, serves as a vital precursor for the synthesis of other pyrimidine nucleotides.

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