- 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

TTP and dCTP (reduction)

De novo pyrimidine nucleotide synthesis builds the pyrimidine ring before attaching it to PRPP. Orotate is synthesized and attached to PRPP to form orotidylate (OMP), which is decarboxylated to UMP. UMP is phosphorylated through UDP to UTP, and UTP is aminated to form CTP.

Michigan State University

Google

De novo nucleotide synthesis pathways construct nucleotide bases from simple precursor molecules such as amino acids, ATP, and CO2. These newly formed bases are ultimately attached to an activated ribose platform, 5-phosphoribosyl-1-pyrophosphate (PRPP), to form complete nucleotides.

There are two primary strategies for de novo synthesis:
- **Pyrimidine de novo synthesis**: The pyrimidine base ring is assembled first and subsequently attached to PRPP.
- **Purine de novo synthesis**: The purine base ring is constructed piece by piece directly onto the pre-existing PRPP structure.

De Novo Nucleotide Synthesis Pathways

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