Uridine monophosphate synthase
Uridine Monophosphate Synthase[edit | edit source]
Uridine monophosphate synthase (UMPS) is a bifunctional enzyme that plays a crucial role in the de novo synthesis of pyrimidine nucleotides. It catalyzes the final two steps in the conversion of orotate to uridine monophosphate (UMP), a precursor for all pyrimidine nucleotides.
Structure and Function[edit | edit source]
UMPS is a multifunctional enzyme composed of two distinct domains: orotate phosphoribosyltransferase (OPRTase) and orotidine-5'-phosphate decarboxylase (OMP decarboxylase). These domains are responsible for the sequential conversion of orotate to UMP.
Orotate Phosphoribosyltransferase (OPRTase)[edit | edit source]
The OPRTase domain catalyzes the reaction between orotate and phosphoribosyl pyrophosphate (PRPP) to form orotidine-5'-monophosphate (OMP). This reaction is the first committed step in the pyrimidine biosynthetic pathway.
Orotidine-5'-Phosphate Decarboxylase[edit | edit source]
The OMP decarboxylase domain subsequently decarboxylates OMP to produce UMP. This reaction is highly efficient and is considered one of the most proficient enzyme-catalyzed reactions known.
Biological Significance[edit | edit source]
UMPS is essential for the synthesis of pyrimidine nucleotides, which are necessary for the synthesis of RNA and DNA. Deficiencies in UMPS activity can lead to orotic aciduria, a rare metabolic disorder characterized by excessive excretion of orotic acid in the urine and associated with megaloblastic anemia.
Genetic and Clinical Aspects[edit | edit source]
The gene encoding UMPS is located on chromosome 3 in humans. Mutations in this gene can lead to hereditary orotic aciduria. Patients with this condition may present with growth retardation, developmental delay, and anemia. Treatment often involves supplementation with uridine, which bypasses the metabolic block.
Related Pages[edit | edit source]
References[edit | edit source]
Uridine monophosphate synthase[edit | edit source]
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