Orotidine 5'-phosphate decarboxylase

Orotidine 5'-phosphate decarboxylase (OMP decarboxylase) is an enzyme that catalyzes the decarboxylation of orotidine monophosphate (OMP) to uridine monophosphate (UMP), a critical step in the de novo synthesis of pyrimidine nucleotides. This reaction is essential for the synthesis of DNA and RNA in all living organisms, making OMP decarboxylase vital for cellular growth and proliferation.

Function

OMP decarboxylase facilitates the conversion of OMP to UMP, removing a carboxyl group in the process. This reaction is highly efficient and has been studied extensively as a model for enzyme catalysis. The enzyme's ability to stabilize the transition state of the reaction is believed to contribute to its catalytic efficiency.

Structure

The structure of OMP decarboxylase varies among different species, but it generally consists of a homodimer, where each monomer contributes to the active site. The enzyme binds to OMP through a network of hydrogen bonds and hydrophobic interactions, positioning it in such a way that facilitates the decarboxylation reaction.

Clinical Significance

Mutations in the gene encoding OMP decarboxylase can lead to orotic aciduria, a rare metabolic disorder characterized by the excretion of large amounts of orotic acid in urine. Patients with orotic aciduria may present with megaloblastic anemia, growth retardation, and developmental delays. Treatment often involves supplementation with uridine.

Inhibitors

OMP decarboxylase is a target for the development of antimetabolites, which are compounds that interfere with the synthesis of nucleotides and are used in the treatment of cancer and viral infections. Specific inhibitors of OMP decarboxylase can potentially reduce the availability of UMP, thereby inhibiting the synthesis of nucleic acids.

Evolution

OMP decarboxylase is considered to be a highly evolved enzyme, with some studies suggesting that it may be one of the most proficient enzymes known. The enzyme's catalytic mechanism and efficiency have been subjects of extensive research, contributing to our understanding of enzyme evolution and catalysis.

See Also

• Pyrimidine biosynthesis
• Nucleotide
• Enzyme catalysis
• Metabolic disorder