肝酸和中链脂肪酸作为中链乙-CoA脱酶缺乏症的阿纳普莱洛斯治疗
Anuradha Karunanidhi1, Shakuntala Basu1, Xue-Jun Zhao1
1Division of Genetic and Genomic Medicine, Department of Pediatrics, School of Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh; Pittsburgh, PA 15224, USA.
Molecular genetics and metabolism
|September 3, 2023
概括
作为中链乙-CoA脱酶 (MCAD) 缺乏症的潜在疗法,三氨酸有效地改善了MCAD缺乏细胞和小鼠的细胞能量代谢. 这表明三胺和分支链脂肪酸可能是MCAD缺乏症的可行治疗方法.
科学领域:
- 生物化学 生物化学
- 代谢障碍 代谢障碍 代谢障碍
- 线粒体医学 线粒体医学
背景情况:
- 特里赫普塔诺因是治疗长链脂肪酸氧化障碍的一种有效的厌敏治疗方法.
- 然而,由于代谢途径不兼容,三类药物在中链乙-CoA脱酶 (MCAD) 缺乏症中是禁忌的.
- 对于患有MCAD缺乏症的患者来说,需要替代性皮性疗法.
研究的目的:
- 为了研究特定脂肪酸 (heptanoic,2,6-dimethylheptanoic,6-amino-2,4-dimethylheptanoic和4,8-dimethylnonanoic酸) 作为对MCAD缺乏症的厌血疗法的潜力.
- 评估这些脂肪酸在改善MCAD缺乏细胞和体内模型中的细胞能量代谢中的有效性.
主要方法:
- 来自MCAD缺陷患者的纤维细胞被用各种脂肪酸治疗.
- 测量了细胞氧气消耗率 (OCR) 和线粒体蛋白质糖化 (表明糖-CoA水平).
- 向的代谢量量化了克雷布斯周期中间体,而体内研究使用了Acadm-/-小鼠接受了triheptanoin治疗.
主要成果:
- 测试中的脂肪酸增强了OCR,并在MCAD缺乏细胞中增加了化,证明了它们作为甲酸CoA来源的作用.
- 缺乏MCAD的细胞可以代谢酸 (C7),但不能代谢酸 (C8).
- 在Acadm-/-小鼠中,用三类药物治疗改善了肝脏病理,增加了糖原含量,并增强了能量平衡.
结论:
- 肝素酸和相关的分支链脂肪酸可以在MCAD缺乏症中作为有效的皮性基质.
- 在一个MCAD缺陷小鼠模型中,三他通过改善能量代谢和逆转肝脏病理来证明治疗潜力.
- 这些发现支持进一步评估三他因和中分支链脂肪酸用于治疗MCAD缺乏症.
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