| Project/Area Number |
61570144
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
SAHEKI Takeyori Department of Biochemistry, Faculty of Medicine, Kagoshima University, 医学部, 教授 (10056070)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Keiko Department of Biochemistry, Faculty of Medicine, Kagoshima University, 医学部, 講師 (70108869)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1987: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Sparse-fur mice / Ornithine transcarbamylase / Hyperammonemia / Urea synthesis / Glutamine / Neurotransmitter / オロト酸 / グルタミン / 神経伝達物質 / sparse-furマウス / 肝臓潅流法 / コンジェニックマウス / ミトルリン |
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| Research Abstract |
In the present study, nitrogen metabolism of sparse-fur (spf). or ornithine transcarbamylase (OTC)-deficient mice was investigated. Spf mice have kinetically abnormal OTC in the liver and intestine,which would cause hyperammonemia and arginine deficiency. The latter was true; they showed low citrulline and arginine concentrations in the serum and in the brain always at the young and old ages. Serum ammonia concentration of spf mice, however, was not elevated at the adult ages. Only during the weaning period for two to three weeks, they showed elevated serum ammonia levels. Considering these results, we compared nitrogen metabolism of spf mice between hyperammonemic stage (30 to 45 days old) and adapted stage (after 50 days old). At hyperammonemic stage, ammonia concentration was elevated in the brain and the level was correlated with the concentrations of glutamine in the brain. And the latter level was corelated with the concentrations of phenylalanine, tyrosine and tryptophan. At this stage,metabolism of 5-hydroxytryptamine was stimulated, as judged from the higher ratio of 5-hydroxytryptamine to 5-hyroxyindole acetic acid. This may cause some neurological symptoms of hyperammonemia. At both stages, levels of citrulline and arginine in the brain were very low. In order to test the ability of ammonia detoxication in the spf mice, liver perfusion experiments were performed. Spf mice showed the lower activity of urea formation from ammonium salt especially under no addition of ornithine. which may be indicative of abnormal kinetic properties of OTC in spf mice. Urinary orotic acid concentration was very high at both stages and is again shown to be a good marker for OTC deficiency.
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