Decreased hyperammonaemia and orotic aciduria due to inactivation of ornithine aminotransferase in mice with a hereditary abnormal ornithine carbamoyltransferase
| Autor: | G Daune-Anglard, Shakir Sarhan, Nikolaus Seiler, B. Knödgen, Christine Grauffel |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Ornithine medicine.medical_specialty Orotic acid Ornithine aminotransferase Biology Excretion chemistry.chemical_compound Mice Ornithine Carbamoyltransferase Ammonia Internal medicine Genetics medicine Citrulline Animals Amino Acids Genetics (clinical) Orotic Acid Behavior Animal Ornithine-Oxo-Acid Transaminase Hyperammonemia medicine.disease Mice Mutant Strains Endocrinology chemistry Mutation Female Orotic aciduria Metabolism Inborn Errors medicine.drug |
| Zdroj: | Journal of inherited metabolic disease. 17(6) |
| ISSN: | 0141-8955 |
| Popis: | Mice with the X-chromosomal sparse-fur (spf) mutation are an animal model of some hereditary deficiencies of ornithine carbamoyltransferase (OCT) in man. Orotic aciduria and hyperammonaemia are the most conspicuous metabolic changes in these diseases. Selective inactivation of ornithine aminotransferase (OAT) by 5-fluoromethylornithine raises endogenous ornithine concentrations so that citrulline formation is effectively catalysed by the aberrant OCT, in spite of its low affinity for ornithine. As a consequence, blood and tissue ammonia concentrations and orotic acid excretion are reduced near to normal values, and the abnormal amino acid patterns in blood, brain and liver are normalized. Selective inactivation of OAT seems a promising therapeutic approach in some hereditary OCT deficiencies, and a total that may allow us to clarify the role of ammonia and orotic acid in the development of nanism and abnormal behaviour in spf mutant mice. |
| Databáze: | OpenAIRE |
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