- 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


CTP (amination) (Cytosine triphosphate)

TTP and dCTP (reduction)

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

Michigan State University

- Add PRPP + amino acids + ATP + CO2 + more
Makes a nucleotide

- 2 different strategies
> Pyrimidine rings are formed first and then are attached to activated ribose (PRPP)
Make UTP and then CTP
>Ribonucleotides that can be used to make RNA
>Then UTP can make TMP and CTP can make dCTP
>Deoxyribonucleotides that can be used to make DNA
 
> Purine rings are formed piece by piece right on the ribose-based structure (PRPP)
> They first make the intermediate IMP
> Then go to ATP and GTP
> Ribonucleotides that can be made into RNA
> ATP can make dATP and GTP can make dGTP
Deoxyribonucleotides that can be used to make DNA


De Novo Pathways (making bases)

Pyrimidine De Novo Pathway

SOURCES OF CARBON AND NITROGEN IN PURINES
- Amino acids: Nitrogen, glutamine, aspartate, glycine, carbons, serine, through N10-formyl THF
- CO2

BIG PICTURE
- We’re going to create an intermediate: IMP
- Then we can make ATP and GTP
> Reduced to purine deoxynucleotides
> dATP, dGTP

STEPS
- Phosphoribosylamine synthesis
- Phosphoribosylamine -> Inosinate and beyond

Learn Before

Related

Learn After