orotate phosphoribosyltransferase activity
Definition
Target type: molecularfunction
Catalysis of the reaction: orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate. [EC:2.4.2.10]
Orotate phosphoribosyltransferase (OPRT) activity catalyzes the transfer of a phosphoribosyl group from 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to orotate, resulting in the formation of orotidine 5'-monophosphate (OMP). This reaction is a crucial step in de novo pyrimidine biosynthesis, a metabolic pathway responsible for the synthesis of the pyrimidine bases uracil and cytosine, essential components of DNA and RNA. OPRT activity is central to this pathway because it is the first committed step in the biosynthesis of pyrimidines.
The reaction proceeds in two steps:
1. **PRPP binding:** The enzyme binds both PRPP and orotate. PRPP is a highly reactive molecule, and its binding to OPRT likely induces conformational changes in the enzyme, facilitating the subsequent transfer reaction.
2. **Phosphoribosyl transfer:** The enzyme catalyzes the transfer of the phosphoribosyl group from PRPP to orotate, forming OMP. This reaction involves the cleavage of the pyrophosphate bond in PRPP, releasing inorganic pyrophosphate (PPi) as a byproduct.
The OPRT active site is characterized by a series of conserved amino acid residues that interact with the substrate molecules, PRPP and orotate. These interactions are crucial for substrate binding and catalysis.
OPRT activity is regulated by various factors, including the availability of substrates, the presence of inhibitors, and the cellular demand for pyrimidines. Dysregulation of OPRT activity can lead to various metabolic disorders, highlighting the importance of this enzyme in maintaining cellular homeostasis and normal physiological function.
This detailed description provides insights into the molecular function of OPRT activity, emphasizing its role in nucleotide biosynthesis and its significance in cell metabolism.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Uridine 5'-monophosphate synthase | A uridine 5-monophosphate synthase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P11172] | Homo sapiens (human) |
Compounds (4)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| uridine monophosphate | uridine 5'-monophosphate : A pyrimidine ribonucleoside 5'-monophosphate having uracil as the nucleobase. Uridine Monophosphate: 5'-Uridylic acid. A uracil nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position. | pyrimidine ribonucleoside 5'-monophosphate; uridine 5'-phosphate | Escherichia coli metabolite; human metabolite; mouse metabolite |
| cytidine monophosphate | cytidine 5'-monophosphate : A pyrimidine ribonucleoside 5'-monophosphate having cytosine as the nucleobase. Cytidine Monophosphate: Cytidine (dihydrogen phosphate). A cytosine nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position. | cytidine 5'-phosphate; pyrimidine ribonucleoside 5'-monophosphate | Escherichia coli metabolite; human metabolite; mouse metabolite |
| 5-fluorouridine 5'-phosphate | 5-fluorouridine 5'-monophosphate : A pyrimidine ribonucleoside 5'-monophosphate having 5-fluorouracil as the pyrimidine component. | organofluorine compound; pyrimidine ribonucleoside 5'-monophosphate | drug metabolite |
| pyrazofurin | pirazofurin : A C-glycosyl compound that is 4-hydroxy-1H-pyrazole-5-carboxamide in which the hydrogen at position 3 has been replaced by a beta-D-ribofuranosyl group. | C-glycosyl compound; pyrazoles | antimetabolite; antimicrobial agent; antineoplastic agent; EC 4.1.1.23 (orotidine-5'-phosphate decarboxylase) inhibitor |