2017年3月
Circulating tricarboxylic acid cycle metabolite levels in citrin-deficient children with metabolic adaptation, with and without sodium pyruvate treatment.
Molecular genetics and metabolism
- 巻
- 120
- 号
- 3
- 開始ページ
- 207
- 終了ページ
- 212
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.ymgme.2016.12.011
- 出版者・発行元
- ACADEMIC PRESS INC ELSEVIER SCIENCE
Citrin deficiency causes adult-onset type II citrullinemia (CTLN-2), which later manifests as severe liver steatosis and life-threatening encephalopathy. Long-standing energy deficit of the liver and brain may predispose ones to CTLN-2. Here, we compared the energy-driving tricarboxylic acid (TCA) cycle and fatty acid beta-oxidation cycle between 22 citrin-deficient children (age, 3-13 years) with normal liver functions and 37 healthy controls (age, 5-13 years). TCA cycle analysis showed that basal plasma citrate and alpha-ketoglutarate levels were significantly higher in the affected than the control group (p < 0.01). Conversely, basal plasma fumarate and malate levels were significantly lower than those for the control (p < 0.001). The plasma level of 3-OH-butyrate derived from fatty acid (3-oxidation was significantly higher in the affected group (p < 0.01). Ten patients underwent sodium pyruvate therapy. However, this therapy did not correct or attenuate such deviations in both cycles. Sodium pyruvate therapy significantly increased fasting insulin secretion (p < 0.01); the fasting sugar level remained unchanged. Our results suggest that citrin-deficient children show considerable deviations of TCA cycle metabolite profiles that are resistant to sodium pyruvate treatment. Thus, long-standing and considerable TCA cycle dysfunction might be a pivotal metabolic background of CTLN-2 development. (C) 2016 Elsevier Inc. All rights reserved.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.ymgme.2016.12.011
- ISSN : 1096-7192
- eISSN : 1096-7206
- PubMed ID : 28041819
- Web of Science ID : WOS:000397080600006