RGD Reference Report - Pyrimidine nucleotide synthesis in the rat kidney in early diabetes. - Rat Genome Database

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Pyrimidine nucleotide synthesis in the rat kidney in early diabetes.

Authors: Kunjara, S  Sochor, M  Ali, M  Drake, A  Greenbaum, AL  McLean, P 
Citation: Kunjara S, etal., Biochem Med Metab Biol. 1991 Oct;46(2):215-25.
RGD ID: 11040445
Pubmed: PMID:1723607   (View Abstract at PubMed)

Early renal hypertrophy of diabetes is associated with increases in the tissue content of RNA, DNA, and sugar nucleotides involved in the formation of carbohydrate-containing macromolecules. We have previously reported an increase in the activity of enzymes of the de novo and salvage pathways of purine synthesis in early diabetes; the present communication explores the changes in the pathways of pyrimidine synthesis. Measurements have been made of key enzymes of the de novo and salvage pathways at 3, 5, and 14 days after induction of diabetes with streptozotocin (STZ), phosphoribosyl pyrophosphate (PPRibP), and some purine and pyrimidine bases. Carbamoyl-phosphate synthetase II, the rate-limiting enzyme of the de novo route, did not increase in the first 5 days after STZ treatment, the period of most rapid renal growth; a significant rise was seen at 14 days (+38%). Dihydroorotate dehydrogenase, a mitochondrial enzyme, showed the most marked rise (+147%) at 14 days. The conversion of orotate to UMP, catalyzed by the enzymes of complex II, was increased at 3 days (+42%), a rise sustained to 14 days. The salvage route enzyme, uracil phosphoribosyltransferase (UPRTase), showed a pattern of change similar to complex II. The effect of the decreased concentration of PPRibP on the activities of CPSII, for which it is an allosteric activator, and on activities of OPRTase and UPRTase, for which it is an essential substrate, is discussed with respect to the relative Ka and Km values for PPRibP and the possibility of metabolite channeling.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DHODHHumanExperimental Diabetes Mellitus  ISODhodh (Rattus norvegicus) RGD 
DhodhRatExperimental Diabetes Mellitus  IEP  RGD 
DhodhMouseExperimental Diabetes Mellitus  ISODhodh (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dhodh  (dihydroorotate dehydrogenase)

Genes (Mus musculus)
Dhodh  (dihydroorotate dehydrogenase)

Genes (Homo sapiens)
DHODH  (dihydroorotate dehydrogenase (quinone))


Additional Information