α-Ketoglutarate coordinates carbon and nitrogen utilization via enzyme I inhibition.
α-Ketoglutarate coordinates carbon and nitrogen utilization via enzyme I inhibition.
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DOI：
10.1038/nchembio.685
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发表时间：
2011-10-16
影响因子：
14.8
通讯作者：
Rabinowitz, Joshua D.
中科院分区：
文献类型：
--
作者：
Doucette, Christopher D.;Schwab, David J.;Wingreen, Ned S.;Rabinowitz, Joshua D.
微生物通过调节其细胞内代谢而在各种营养环境中存活。平衡生长需要协调碳和氮的吸收，这是生物质生产的主要基质。然而，平衡碳和氮吸收的机制知之甚少。我们发现，在大肠杆菌中，氮供应量的突然增加导致葡萄糖摄取几乎立即增加。然而，已知的糖酵解中间体和调节剂的浓度保持稳态。相反，我们发现在氮限制下积累的α-酮戊二酸通过抑制酶I（磷酸转移酶系统（PTS）的第一步）直接阻断葡萄糖摄取。这使得能够通过同时加速葡萄糖输入和末端糖酵解中间体磷酸烯醇丙酮酸的消耗来快速调节糖酵解通量，而不会使糖酵解中间体的浓度发生显著变化。定量建模表明，这种以前未识别的监管连接原则上足以协调碳和氮的利用。
Microbes survive in a variety of nutrient environments by modulating their intracellular metabolism. Balanced growth requires coordinated uptake of carbon and nitrogen, the primary substrates for biomass production. The mechanisms that balance carbon and nitrogen uptake are, however, poorly understood. We find in Escherichia coli that a sudden increase in nitrogen availability results in an almost immediate increase in glucose uptake. The concentrations of known glycolytic intermediates and regulators, however, remain homeostatic. Instead, we find that α-ketoglutarate, which accumulates in nitrogen limitation, directly blocks glucose uptake by inhibiting Enzyme I, the first step of the phosphotransferase system (PTS). This enables rapid modulation of glycolytic flux without marked concentration changes in glycolytic intermediates by simultaneously accelerating glucose import and consumption of the terminal glycolytic intermediate phosphoenolpyruvate. Quantitative modeling shows that this previously unidentified regulatory connection is in principle sufficient to coordinate carbon and nitrogen utilization.
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DOI：
10.1016/0006-291x(92)91861-j
发表时间：
1992-02-14
影响因子：
3.1
作者：
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通讯作者：
PETERKOFSKY, A
影响因子：
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DOI：
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发表时间：
2007-05-01
影响因子：
3.2
作者：
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通讯作者：
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影响因子：
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作者：
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