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ATGL 是氧脂肪酸脂肪酸的生物合成酶
Rucha Patel1, Anna Santoro1, Peter Hofer2
1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Nature
|June 8, 2022
概括
脂肪甘油脂酶 (ATGL) 是第一个合成基脂肪酸 (FAHFA) 脂肪酸的酶. 这一发现揭示了ATGL
科学领域:
- 脂质生物化学
- 酵素学
- 代谢疾病研究
背景情况:
- 基脂肪酸的脂肪酸 (FAHFA) 是哺乳动物中发现的新型脂质.
- 一个亚家族,酸酸 (PAHSAs) 的棕酸,表现出抗炎和抗糖尿病的特性.
- 降低PAHSA水平与人类和小鼠的胰岛素抵抗有关.
研究的目的:
- 在体内确定负责FAHFA生物合成的酶.
- 阐明被识别的酶催化FAHFA形成的机制.
主要方法:
- 使用化学生物学和蛋白质组学来确定候选酶.
- 进行了重组酶活性测试以确认催化功能.
- 用小鼠和细胞模型进行基因淘汰和过度表达研究.
主要成果:
- 脂肪三糖 lipase (ATGL) 被确定为FAHFA生物合成中的关键酶.
- 通过使用甘油三或甘油二的转化反应,ATGL催化了FAHFA的形成.
- 基因删除或ATGL的化学抑制显著降低了内源性FAHFA和FAHFA-TG水平.
结论:
- 在FAHFA合成过程中,ATGL具有前所未知的关键性交易酶活性.
- 这一发现确定ATGL是第一个被发现的催化FAHFA结的哺乳动物酶.
- 在代谢和炎症性疾病中,ATGL的晶酶活性具有潜在的临床意义.
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