能量代谢对于所有活细胞都至关重要，尤其是在快速生长或应激情况下。许多癌症和激活的免疫细胞（瓦伯格效应）或酵母（克拉布特里效应）主要依靠有氧葡萄糖发酵分别产生乳酸或乙醇来产生 ATP。近年来，人们提出了几种数学模型来从理论上解释瓦尔堡效应。除了葡萄糖之外，谷氨酰胺是真核细胞非常重要的底物——不仅用于生物合成，还用于能量代谢。在这里，我们提出了一个基于最小约束的化学计量模型，用于解释经典的 Warburg 效应和实验观察到的谷氨酰胺呼吸发酵（WarburQ 效应）。我们考虑葡萄糖和谷氨酰胺呼吸以及各自的发酵途径。我们的资源分配模型计算 ATP 生产率，同时考虑酶质量以及途径成本。虽然我们的计算预测葡萄糖发酵是人类细胞中一种优越的能量产生途径，但酵母中不同的酶特性降低了这种优势，在某些情况下，葡萄糖呼吸是首选的程度。后者是针对真菌病原体白色念珠菌观察到的，它是一种已知的克拉布特里阴性酵母。此外，优化结果表明，谷氨酰胺除了在真核细胞中作为生物量的碳源和氮源外，还是葡萄糖限制下的宝贵能源和重要底物。总之，我们的模型提供了这样的见解：在快速生长和感染情况下，谷氨酰胺是真核细胞的一种被低估的燃料，并很好地解释了在几种细胞类型中观察到的葡萄糖和谷氨酰胺的平行呼吸发酵。© 2024。作者。

Energy metabolism is crucial for all living cells, especially during fast growth or stress scenarios. Many cancer and activated immune cells (Warburg effect) or yeasts (Crabtree effect) mostly rely on aerobic glucose fermentation leading to lactate or ethanol, respectively, to generate ATP. In recent years, several mathematical models have been proposed to explain the Warburg effect on theoretical grounds. Besides glucose, glutamine is a very important substrate for eukaryotic cells-not only for biosynthesis, but also for energy metabolism. Here, we present a minimal constraint-based stoichiometric model for explaining both the classical Warburg effect and the experimentally observed respirofermentation of glutamine (WarburQ effect). We consider glucose and glutamine respiration as well as the respective fermentation pathways. Our resource allocation model calculates the ATP production rate, taking into account enzyme masses and, therefore, pathway costs. While our calculation predicts glucose fermentation to be a superior energy-generating pathway in human cells, different enzyme characteristics in yeasts reduce this advantage, in some cases to such an extent that glucose respiration is preferred. The latter is observed for the fungal pathogen Candida albicans, which is a known Crabtree-negative yeast. Further, optimization results show that glutamine is a valuable energy source and important substrate under glucose limitation, in addition to its role as a carbon and nitrogen source of biomass in eukaryotic cells. In conclusion, our model provides insights that glutamine is an underestimated fuel for eukaryotic cells during fast growth and infection scenarios and explains well the observed parallel respirofermentation of glucose and glutamine in several cell types.© 2024. The Author(s).