饥饿是一种多功能纯素酶,可实现纯素核酸循环
M Zaeem Cader1, Rodrigo Pereira de Almeida Rodrigues1, James A West2
1Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Cell
|January 25, 2020
概括
这种功能在真核生物中以前是未知的. 这一发现揭示了
科学领域:
- 生物化学
- 分子生物学
- 遗传学
背景情况:
- 在FAMIN中发生的突变与早期发病的关节炎和炎症性肠病有关.
- 一种常见的FAMIN基因变异增加了克罗恩病和麻风的易感性.
研究的目的:
- 通过不偏的查方法确定孤儿蛋白FAMIN的酶活性.
- 阐明FAMIN在真核细胞,特别是巨细胞中的代谢作用.
主要方法:
- 开发一个无偏的液体染色体质谱屏幕来检测酶活性.
- 生物化学测定以描述FAMIN的腺裂变.
- 在涉及FAMIN的巨细胞中分析 purin核酸循环 (PNC).
主要成果:
- 发现FAMIN可将腺分解为腺和核糖-1-酸盐,这是以前在真核生物中未发现的活性.
- FAMIN及其 prokaryotic 正基体表现出腺脱氨酶,纯核酸酸化酶和S-甲基-5'-thioadenosine酸化酶的活动.
- FAMIN促进巨细胞中的纯氨酸核酸循环,将脂肪酸氧化和ATP酸酶活动联系起来,以同步线粒体呼吸和糖解.
结论:
- 在真核生物中,FAMIN具有对 purin代谢至关重要的新型酶活性.
- 由FAMIN调节的巨蛋白核酸循环在平衡细胞能量代谢中起着关键作用.
- 这一发现为了解和治疗FAMIN相关的炎症疾病开辟了新的途径.
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