Genetic and environmental factors related to onset and severity of CTLN2 in citrin deficiency

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09595
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kagoshima University
• Principal Investigator: Saheki Takeyori 鹿児島大学, 医歯学総合研究科, 客員研究員 (10056070)
• Co-Investigator(Kenkyū-buntansha): 井ノ上 逸朗 国立遺伝学研究所, 総合遺伝研究系, 教授 (00192500) ; 矢崎 正英 信州大学, 学術研究院保健学系, 教授 (70372513) ; 森山 光章 大阪府立大学, 生命環境科学研究科, 准教授 (20275283)
• Research Collaborator: FUNAHASHI Aki 鹿児島大学, 医歯学総合研究科 ; KURODA Eishi 鹿児島大学, 医歯学総合研究科 ; YASUDA Izumi 鹿児島大学, 医歯学総合研究科 ; SETOGAWA Yoshiko 鹿児島大学, 医歯学総合研究科
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: citrin deficiency / CTLN2 / hyperammonemia / sugar toxicity / NADH / ornithine / aspartate / alanine

Outline of Final Research Achievements

Aversion against sugars is the remarkable characteristics of citrin deficiency. We showed that two factors simultaneously induced by sugar intake, an increased cytosolic NADH and decreased ATP in the liver, send signals to the brain, to avoid intake of excess sugars.
On the other hand, we have shown that intake of protein and some amino acids ameliorate sugar toxicity. In this research, we clarified that a severe hyperammonemia induced in the model mice was greatly relieved by oral administration of ornithine + aspartate or alanine. Although aspartate can’t directly enter the hepatocyte carrying urea cycle, it can be converted into alanine in the small intestine, which then can enter the hepatocyte with urea cycle and converted back to aspartate, resulting in almost complete dissolution of hyperammonemia.

Free Research Field

病態生化学