Official Full Name
OPRTase
Background
Orotate phosphoribosyltransferase (OPRTase) or Orotic acid phosphoribosyltransferase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotate and phosphoribosyl pyrophosphate. In yeast and bacteria, orotate phosphoribosyltransferase is an independent enzyme with a unique gene coding for the protein, whereas in mammals and other multicellular organisms, the catalytic function is carried out by a domain of the bifunctional enzyme UMP synthase.
Synonyms
orotidylic acid phosphorylase; orotidine-5'-phosphate pyrophosphorylase; OPRTase; orotate phosphoribosyl pyrophosphate transferase; orotic acid phosphoribosyltransferase; orotidine 5'-monophosphate pyrophosphorylase; orotidine monophosphate pyrophosphorylase; orotidine phosphoribosyltransferase; orotidylate phosphoribosyltransferase; orotidylate pyrophosphorylase; orotidylic acid pyrophosphorylase; orotidylic phosphorylase; orotidylic pyrophosphorylase; EC 2.4.2.10; 9030-25-5
Ornithine phosphoribosyltransferase, also known by its abbreviation OPRTase, is an essential enzyme found ubiquitously in intestinal microorganisms, plants, and animals. OPRTase plays a critical role in the biosynthesis of pyrimidine nucleotides, a key process required for DNA and RNA synthesis. Given its role in critical cellular functions, it is an area of interest in the scientific community and medical research for its potential in disease treatment.
Introductions
OPRTase is responsible for the third step of the pyrimidine biosynthesis pathway – participating in the conversion of orotate into orotidine-5'-monophosphate (OMP), an essential step in pyrimidine nucleotide biosynthesis. It catalyzes the transfer of the phosphoribosyl group from 5-phosphoribosyl-1- pyrophosphate (PRPP) to orotate to form OMP and pyrophosphate. Activity of OPRTase is vital in maintaining the balance of pyrimidine nucleotides in cells. Besides, changes in enzyme activity have been linked to various pathological conditions, making it an important target for potential therapeutic interventions.
Structure
OPRTase has a complex and unique structure that contributes to its functionality. The enzyme generally exists as an oligomer, often in a hexagonal or dodecameric configuration. Each of its subunits has a unique shape with a compact alpha/beta core. The active site is located in the cleft formed by these structural elements. This structural organization enables OPRTase to exhibit a high substrate specificity and catalytic efficiency.
Mechanisms
The catalytic reaction mechanism of OPRTase is a two-step process. Initially, pyrophosphate is released from PRPP, forming an enzyme-PRPP complex. Then, orotate is bound, and the phosphoribosyl group is transferred to orotate to generate OMP. Two essential aspartate residues in the active site of OPRTase play a crucial role in this catalysis mechanism. They function as general acid-base catalysts, participating in proton transfer during the reaction.
Applications
OPRTase is a potential therapeutic target for several pathologic conditions. It is significantly implicated in various cancers, autoimmune diseases, and infectious diseases. The pharmacological manipulation of OPRTase can achieve a therapeutic effect by altering nucleotide metabolism, influencing many aspects of cell function. OPRTase inhibitors can be used to block the proliferation of cancer cells, suppress the immune response in autoimmune diseases, or inhibit microbial growth in infectious diseases.
Clinical Significance
The clinical relevance of OPRTase is primarily centered on its role in cell growth and proliferation, particularly in relation to cancer. The overexpression of OPRTase has been linked to several cancers such as colorectal and breast cancer. In these contexts, its abnormal activation promotes the uncontrolled proliferation of cancer cells. Therapeutic approaches that target the OPRTase pathway have shown potential in a number of clinical trials. Measurement of OPRTase activity or presence can also function as a diagnostic marker for certain diseases.
Conclusion
In conclusion, OPRTase is a key enzyme involved in cell replication and growth and has high clinical relevance in the potential treatment of various diseases. Through the understanding of its structure and catalytic mechanism, we come closer to seeing its full application and understanding its importance fully. Unraveling the complexities of this enzyme will allow for innovative interventions in treating various forms of cancer, infectious, and autoimmune diseases. The potential it holds within biochemical, biomedical, and therapeutic applications cannot be overestimated.
