对调节酵母代谢流量的系统级分析
Sean R Hackett1, Vito R T Zanotelli2, Wenxin Xu3
1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Science (New York, N.Y.)
|October 30, 2016
概括
代谢物度,而不是酶水平,主要控制细胞反应速率. 这项研究确定了新的交叉通道规则,揭示了酸盐等代谢物如何影响酵母代谢中的关键酶.
科学领域:
- 生物化学
- 系统生物学
- 代谢工程
背景情况:
- 细胞代谢流是由酶活动和代谢物度控制的.
- 传统的生物化学方法往往无法捕捉不同生理状态的动态度变化.
- 了解调节需要将酶动力学与代谢物和酶丰度数据整合起来.
研究的目的:
- 量化酵素和代谢物度以及酵母中的代谢流量.
- 确定酶和代谢物水平对代谢调节的相对贡献.
- 识别和生化验证交叉途径代谢调节的实例.
主要方法:
- 在25种稳定状态酵母培养物中测量酶和代谢物度和代谢流量.
- 应用迈凯利斯-门动力学来评估度与反应速率之间的关系.
- 对已识别的交叉通道调节机制进行生物化学验证.
主要成果:
- 基质度被确定为细胞净代谢反应率的最强的驱动因素.
- 代谢物度对代谢流量的生理影响是酶度的两倍多.
- 发现了三种新型的交叉通路调节,包括酸抑制酸激酶.
结论:
- 在调节细胞代谢方面,代谢物度比酶度更为主导.
- 通过酸激酶,发现酸积累抑制了限酵母中的糖溶性外流.
- 这项研究为了解代谢调节和交叉途径相互作用提供了定量框架.
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