| Project/Area Number |
10470172
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
NARISAWA Kuniaki MEDICAL GENETICS, TOHOKU UNIV., PROFESSOR, 大学院・医学系研究科, 教授 (90004647)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yoichi MEDICAL GENETICS, TOHOKU UNIV., ASSOCIATE RESEARCHER, 大学院・医学系研究科, 助手 (80216457)
KURE Shigeo MEDICAL GENETICS, TOHOKU UNIV., ASSOCIATE RESEARCHER, 大学院・医学系研究科, 助手 (10205221)
MATSUBARA Yoichi MEDICAL GENETICS, TOHOKU UNIV., ASSOCIATE PROFESSOR, 大学院・医学系研究科, 助教授 (00209602)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1999: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1998: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | BIOTIN / HOLOCARBOXYLASE SYNTHETASE DEFICIENCY / MUTATION / KINETICO / MULTIPLE CARBOXYLASE DEFICIENCY / Vmax値 / 開始コドン / ペプチド抗体 / ウエスタンブロット / ピオチン反応性 |
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| Research Abstract |
Holocarboxylase synthetase (HCS) deficiency is a metabolic disorder causing a biotin-responsive multiple carboxylase deficiency. We analyzed the kinetic property of several mutant HCS proteins. Two mutants located within the putative biotin-binding site of HCS showed elevated Km values for biotin compared to those of the wild-type form. On the other hand, the remaining five mutations were outside of the biotin-binding site. The enzymes containing these mutations showed normal or low Km values for biotin (non-Km mutant). Symptoms of patients who have the non-Km mutants, as well as those of patients who have the Km mutants, responded to biotin therapy. The responsiveness to biotin supplement of propionyl-CoA carboxylase activity in cultured cells bearing some of these mutations correlated well to the corresponding reduction in the Vmax. Patients who have mutant HCS proteins with lower Vmax showed poor clinical and biochemical responses to biotin therapy. The determination of HCS genotype can be valuable for characterizing the clinical phenotype in HCS deficient patients.
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