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Characteristics of NO cycle coupling with urea cycle in non-hyperammonemic carriers of ornithine transcarbamylase deficiency
- Source :
- Molecular Genetics and Metabolism. 109:251-254
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Urea cycle deficient patients with prominent hyperammonemic often exhibit abnormal production of nitric oxide (NO), which reduces vascular tone, along with amino acid abnormalities. However, information related to the metabolic changes in heterozygotes of ornithine transcarbamylase deficiency (OTCD) lacking overt hyperammonemia is quite limited. We examined vascular mediators and amino acids in non-hyperammonemic heterozygotes. Twenty-four heterozygous OTCD adult females without hyperammonemic bouts, defined as non-hyperammonemic carriers, were enrolled. We measured blood amino acids constituting urea cycle and nitric oxide (NO) cycle. Blood concentrations of nitrate/nitrite (NOx) as stable NO-metabolites, asymmetric dimethylarginine (ADMA) inhibiting NO synthesis, and endothelin-1 (ET-1) raising vascular tone were also determined. NOx concentrations were significantly lower in non-hyperammonemic carriers (p < 0.01). However, ADMA and ET-1 levels in this group were comparable to those in the age-matched control group. Arginine and citrulline levels were also significantly lower in non-hyperammonemic carriers than in controls (p < 0.01). Of the 24 non-hyperammonemic carriers, 10 often developed headaches. Their daily NOx and arginine levels were significantly lower than those in headache-free carriers (p < 0.05). In three carriers receiving oral l-arginine, blood NOx concentrations were significantly higher. In two of those three, the occurrence of headaches was decreased. These results suggest that NO cycle coupling with the urea cycle is altered substantially even in non-hyperammonemic OTCD carriers, predisposing them to headaches.
- Subjects :
- Male
Heterozygote
medicine.medical_specialty
Arginine
Endocrinology, Diabetes and Metabolism
Ornithine Carbamoyltransferase Deficiency Disease
Nitric Oxide
Biochemistry
chemistry.chemical_compound
Endocrinology
Ammonia
Internal medicine
Genetics
Citrulline
medicine
Humans
Urea
Amino Acids
Molecular Biology
Ornithine transcarbamylase deficiency
Endothelin-1
Infant, Newborn
Infant
Hyperammonemia
medicine.disease
Arginase
chemistry
Child, Preschool
Urea cycle
Female
Asymmetric dimethylarginine
Metabolic Networks and Pathways
Subjects
Details
- ISSN :
- 10967192
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Molecular Genetics and Metabolism
- Accession number :
- edsair.doi.dedup.....3f5b0a1ed22835ed960bd7709681778a
- Full Text :
- https://doi.org/10.1016/j.ymgme.2013.04.013