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The molecular types were recently confirmed by RFLP analysis of the orotidine monophosphate pyrophosphorylase (URA5) gene and the phospholipase (PLB1) gene.
Uremic Toxins with Similarities Purine Derivatives: Cytidine, hypoxanthine, xanthine, uric acid Pyrimidine Derivatives:_Thymine, orotic acid, orotidine, uridine Methyl amine Derivatives:_Methylamine, dimethylamine, trimethylamine Indole Derivatives: Kynurenine, indole-3-acetate, kynurenic acid, melatonin, indoxyl sulfate, quinolinic acid.
Number of Name of metabolite HDMB number Level in metabolite in serum serum 1 Pyridoxine HMDB00239 [down arrow] 2 Orotidine HMDB00788 [down arrow] 3 S-adenosylhomocysteine HMDB00939 [down arrow] 4 Pyridoxamine HMDB01431 [down arrow] 5 Glycocholic acid HMDB00138 [down arrow] 6 Beta-leucine HMDB03640 [down arrow] 7 5-Methylcytidine HMDB00982 [down arrow] 8 Taurocholic acid HMDB00036 [down arrow] 9 3-Hydroxybutyric acid HMDB00357 [down arrow] 10 7-Ketocholesterol HMDB00501 [down arrow] 11 3-Hydroxyisovaleric acid HMDB00754 [down arrow] 12 L-fucose HMDB00174 [down arrow] 13 Cholesterol HMDB00067 [down arrow] 14 L-palmitoylcarnitine HMDB00222 [down arrow] 15 Glycine HMDB00123 [up arrow] Differentiating metabolites detected from their chemical shifts and identified by HDMB.
One example of these markers is the URA3 gene that encodes orotidine 5-monophosphate decarboxylase (OMPD Case), an enzyme involved in the de novo synthesis of pyrimidine ribonucleotides (10).
Resistance to 5-FOA can be achieved by blocking the pyrimidine pathway through mutational inactivation of orotidine-5'-monophosphate (OMP) decarboxylase which catalyzes the decarboxylation of orotidine monophosphate (OMP) to form uridine monophosphate (UMP).
The URA3 enzyme (orotidine 5'-phosphate decarboxylase, ODCase) is involved in the metabolic pathway of uridyl-monophosphate (UMP), which is a substrate of thymidylate synthetase and UMP kinase, both involved in nucleic acid synthesis.
The addition of dichloroallyl lawsone (DCL) to leukemic cells results in a rapid depletion of uridine and cytidine nucleotides; carbamyl aspartate and dihydroorotate accumulate to high levels in an equilibrium ratio of 20.5:1 and orotate, orotidine and uridine-monophosphate (UMP) increase transiently before decreasing to levels approaching their original steady states (Kempt 1986).
In contrast, patients suffering from a urea-cycle disorder can, in addition to orotate, also excrete highly increased amounts of orotidine, uridine, and uracil (5, 7).
To this effect, 340 clinical, veterinary, and environmental isolates from Argentina, Brazil, Chile, Colombia, Mexico, Peru, Venezuela, Guatemala, and Spain were typed by using M13 polymerase chain reaction-fingerprinting and orotidine monophosphate pyrophosphorylase (URA5) gene restriction fragment length polymorphsm analysis with Hhal and Sau961 in a double digest.