Orotic Acid (orotic + acid)

Distribution by Scientific Domains


Selected Abstracts


A Caenorhabditis elegans model of orotic aciduria reveals enlarged lysosome-related organelles in embryos lacking umps-1 function

FEBS JOURNAL, Issue 6 2010
Steven Levitte
Gut granules are cell type-specific lysosome-related organelles found within the intestinal cells of Caenorhabditis elegans. To investigate the regulation of lysosome-related organelle size, we screened for C. elegans mutants with substantially enlarged gut granules, identifying alleles of the vacuolar-type H+ -ATPase and uridine-5,-monophosphate synthase (UMPS)-1. UMPS-1 catalyzes the conversion of orotic acid to UMP; this comprises the two terminal steps in de novo pyrimidine biosynthesis. Mutations in the orthologous human gene UMPS result in the rare genetic disease orotic aciduria. The umps-1(,) mutation promoted the enlargement of gut granules to 250 times their normal size, whereas other endolysosomal organelles were not similarly affected. UMPS-1::green fluorescent protein was expressed in embryonic and adult intestinal cells, where it was cytoplasmically localized and not obviously associated with gut granules. Whereas the umps-1(,) mutant is viable, combination of umps-1(,) with mutations disrupting gut granule biogenesis resulted in synthetic lethality. The effects of mutations in pyr-1, which encodes the enzyme catalyzing the first three steps of de novo pyrimidine biosynthesis, did not phenotypically resemble those of umps-1(,); instead, the synthetic lethality and enlargement of gut granules exhibited by the umps-1(,) mutant was suppressed by pyr-1(,). In a search for factors that mediate the enlargement of gut granules in the umps-1(,) mutant, we identified WHT-2, an ABCG transporter previously implicated in gut granule function. Our data suggest that umps-1(,) leads to enlargement of gut granules through a build-up of orotic acid. WHT-2 possibly facilitates the increase in gut granule size of the umps-1(,) mutant by transporting orotic acid into the gut granule and promoting osmotically induced swelling of the compartment. [source]


Capillary Zone Electrophoresis of some organic acids in milk whey

JOURNAL OF SEPARATION SCIENCE, JSS, Issue 5 2003
Francesca Buiarelli
Abstract This paper describes a method for analysing some acids of milk whey by Capillary Zone Electrophoresis. After eliminating the whey proteins by ultrafiltration, the whey underwent electrophoretic separation in the presence of anodic electroosmotic flow. The following analytes were detected: citric, orotic, uric, and hippuric acids. A procedure is described for sample preparation and the operating conditions for electrophoretic capillary separation established. Finally, orotic acid is quantitatively determined. [source]


Pyrimidine nucleotide and nucleic acid synthesis in embryos and megagametophytes of white spruce (Picea glauca) during germination

PHYSIOLOGIA PLANTARUM, Issue 1 2002
Claudio Stasolla
Pyrimidine nucleotide synthesis was investigated in isolated germinating zygotic embryos and separated megagametophytes of white spruce by following the metabolic fate of 14C-labelled orotic acid, uridine, and uracil, as well as by measuring the activities of the major enzymes participating in nucleotide synthesis. The rate of nucleic acid synthesis in these tissues was also examined by tracer experiments and autoradiographic studies conducted with labelled thymidine, and by conventional light microscopy. From our results, it emerges that changes in the contribution of the de novo and salvage pathways of pyrimidines play an important role during the initial stages of zygotic embryo germination. Preferential utilization of uridine for nucleic acid synthesis, via the salvage pathway, was observed at the onset of germination, before the restoration of a fully functional de novo pathway. Similar metabolic changes, not observed in the gametophytic tissue, were also documented in somatic embryos previously. These alterations of the overall pyrimidine metabolism may represent a strategy for ensuring the germinating embryos with a large nucleotide pool. Utilization of 14C-thymidine for nucleic acid synthesis increased in both dissected embryos and megagametophytes during germination. Autoradiographic and light microscopic studies indicated that soon after imbibition, DNA synthesis was preferentially initiated along the embryonic axis, especially in the cortical cells. Apical meristem reactivation was a later event, and the root meristem became activated before the shoot meristem. Taken together, these results indicate that precise changes in nucleotide and nucleic acid metabolism occur during the early phases of embryo germination. [source]


Acute hyperammonaemic encephalopathy in a female newborn caused by a novel, de novo mutation in the ornithine transcarbamylase gene

ACTA PAEDIATRICA, Issue 5 2004
D Valik
A full-term female offspring of a first and uneventful pregnancy presented at 60 h of life with irritability, tachypnea and respiratory alkalosis progressing to deep coma with clinically dominant circulatory failure, tachycardia and hypotension. Diagnosis of ornithine transcarbamylase (OTC) deficiency was made on the basis of hyperammonaemia, hypocitrullinaemia and extreme hyper-excretion of orotic acid. The baby was treated with peritoneal dialysis, arginine hydrochloride and adequate energy supply. DNA analysis revealed an as of yet unidentified missense mutation in the 6th exon of the OTC gene, resulting in a change of lysine to glutamine at position 210 (K210Q). Her parents were not found to carry this mutation, implying that this mutation may have occurred either de novo in the patient or in a parental germ cell. Conclusion: An acute neonatal form of OTC deficiency should be considered in the differential diagnosis of coma in female newborns. [source]