Disease relevance of UMPS

• Expression of human UMP synthase cDNAs containing these mutations in pyrimidine auxotrophic Escherichia coli and in recombinant baculovirus-infected Sf21 cells demonstrates impaired activity presumably associated with the urinary orotic acid substrate accumulations observed in vivo [1].
• UMP synthase, or multienzyme pyr-5,6 (orotate phosphoribosyltransferase:orotidine monophosphate decarboxylase), has been purified from Ehrlich ascites carcinoma to apparent homogeneity [2].
• The baculovirus system was used to express human UMP synthase because it usually yields a product with posttranslational modifications that reflect those of the organism that provided the cDNA [3].

High impact information on UMPS

• Decreased expression of UMPS in tubers led to an increase in transcript levels of carbamoylphosphate synthase, uridine kinase, and uracil phosphoribosyltransferase, the latter two encoding enzymes in the pyrimidine salvage pathways [4].
• In this study, we investigate the influence of a decreased expression of UMP synthase (UMPS), a key enzyme in the pathway of de novo pyrimidine synthesis, on biosynthetic processes in growing potato (Solanum tuberosum) tubers [4].
• The UMP synthase genomic structure encodes six exons ranging in size from 115 bp to 672 bp, and all splicing junctions adhere to the canonical GT/AG rule [1].
• Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families [1].
• We have isolated the UMP synthase chromosomal gene from a lambdaEMBL-3 human genomic library and report a single-copy gene spanning approximately 15 kb [1].

Chemical compound and disease context of UMPS

• Isolation and initial characterization of the single polypeptide that synthesizes uridine 5'-monophosphate from orotate in Ehrlich ascites carcinoma. Purification by tandem affinity chromatography of uridine-5'-monophosphate synthase [2].
• We have previously reported that UMP synthase from mouse Ehrlich ascites cells can exist in at least three distinct aggregation and/or conformation states, as measured by changes in sedimentation through sucrose gradients [Traut, T. W., & Jones, M. E. (1979) J. Biol. Chem, 254, 1143-1150] [5].

Biological context of UMPS

• Localization of uridine monophosphate synthase (UMPS) gene to river buffalo chromosomes by FISH [6].
• The COOH-terminal 258 amino acids of the human UMP synthase protein contain the orotidine-5'-monophosphate decarboxylase catalytic domain [7].
• Molecular cloning and nucleotide sequence for the complete coding region of human UMP synthase [7].
• A human T-lymphoblastic cell cDNA library constructed in lambda gt10 was screened with a UMP synthase-specific rat cDNA probe [7].
• We used a human cDNA probe to localize the gene for UMP synthase to human chromosome region 3q13 by the technique of in situ hybridization [8].

Anatomical context of UMPS

• HPLC assay of uridine monophosphate synthase (UMPS) in chorionic villus samples (CVS) and erythrocytes (RBC) [9].
• Cell lines from three orotic aciduria patients have been characterized for UMP synthase gene and mRNA content [10].
• Analysis of UMP synthase gene and mRNA structure in hereditary orotic aciduria fibroblasts [10].
• Characterization of pyrazofurin-resistant HeLa cells with amplification of UMP synthase gene [11].
• Western blot analysis, immunofluorescent microscopy and immunoelectron microscopy confirmed that CAD and UMP synthase are found in the cytoplasm around and outside the mitochondria; DHODH is found exclusively inside the mitochondria [12].

Associations of UMPS with chemical compounds

• Decreased expression of UMPS restricted the use of externally supplied orotate for de novo pyrimidine synthesis in tuber tissue, whereas the uridine-salvaging pathway was stimulated [4].
• UMP synthase is a bifunctional enzyme containing the two activities orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase, which catalyze the two-step conversion of orotic acid to UMP [10].
• UMP synthase in extracts from deficient cells is more readily denatured by heat and is stabilized after growth of cells in 6-azauridine [13].
• Orotic aciduria (type 1) results from a mutation in the gene for UMP synthase, a bifunctional protein containing the two enzyme activities which convert orotic acid and 5-phosphoribosyl-1-pyrophosphate to UMP and CO2 [13].
• We report data to show that human UMP synthase derived from either human placenta or larval extracts both have a sequence in which the N-terminal methionine has been removed and the formerly penultimate alanine has been acetylated [3].

Enzymatic interactions of UMPS

• UMP synthase catalyzes the conversion of orotic acid to orotidine 5'-monophosphate (OMP) and then OMP to UMP [14].

Other interactions of UMPS

• This fragment produced increased transcriptional activity in reporter gene constructs containing either the MGMT or UMP-synthase promoter when transfected into either of two cell lines; it seems therefore that this enhancer may interact with relatively common trans-acting factors [15].

Analytical, diagnostic and therapeutic context of UMPS

• This HPLC assay can easily detect picomole levels of UMP in enzymatic reactions using low specific activity UMPS of mammalian cell extracts, which is difficult to do with the other nonradioactive assays that have been described [16].
• A 28.6-kDa ODC protein band and a 24.4-kDa OPRT band were detected on western blots with UMP synthase-specific polyclonal antiserum [17].

References