Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Carrera de Biología, Laboratorio de Control Metabólico, Los Reyes Ixtacala, Hab. Los Reyes Ixtacala Barrio de los Árboles/Barrio de los Héroes, Tlalnepantla, 54090, Mexico.
Instituto Nacional de Cardiología, Departamento de Bioquímica, Ciudad de México, 14080, Mexico.
Arch Biochem Biophys. 2023 May 1;739:109559. doi: 10.1016/j.abb.2023.109559. Epub 2023 Mar 9.
Glycolytic and respiratory fluxes were analyzed in cancer and non-cancer cells. The steady-state fluxes in energy metabolism were used to estimate the contributions of aerobic glycolytic and oxidative phosphorylation (OxPhos) pathways to the cellular ATP supply. The rate of lactate production - corrected for the fraction generated by glutaminolysis - is proposed as the appropriate way to estimate glycolytic flux. In general, the glycolytic rates estimated for cancer cells are higher than those found in non-cancer cells, as originally observed by Otto Warburg. The rate of basal or endogenous cellular O consumption corrected for non-ATP synthesizing O consumption, measured after inhibition by oligomycin (a specific, potent and permeable ATP synthase inhibitor), has been proposed as the appropriate way to estimate mitochondrial ATP synthesis-linked O flux or net OxPhos flux in living cells. Detecting non-negligible oligomycin-sensitive O consumption rates in cancer cells has revealed that the mitochondrial function is not impaired, as claimed by the Warburg effect. Furthermore, when calculating the relative contributions to cellular ATP supply, under a variety of environmental conditions and for different types of cancer cells, it was found that OxPhos pathway was the main ATP provider over glycolysis. Hence, OxPhos pathway targeting can be successfully used to block in cancer cells ATP-dependent processes such as migration. These observations may guide the re-design of novel targeted therapies.
分析了癌症和非癌细胞中的糖酵解和呼吸通量。通过能量代谢的稳态通量来估计有氧糖酵解和氧化磷酸化（OxPhos）途径对细胞 ATP 供应的贡献。已提出校正谷氨酸分解产生的那部分乳酸产量的方法，作为估计糖酵解通量的适当方法。通常，正如 Otto Warburg 最初观察到的那样，癌症细胞中的糖酵解速率高于非癌细胞中的糖酵解速率。校正非 ATP 合成 O 消耗后的基础或内源性细胞 O 消耗率，在寡霉素（一种特异性、强效和可渗透的 ATP 合酶抑制剂）抑制后进行测量，已被提议作为估计活细胞中线粒体 ATP 合成相关 O 通量或净 OxPhos 通量的适当方法。在癌症细胞中检测到不可忽略的寡霉素敏感 O 消耗率，表明线粒体功能未受损，这与 Warburg 效应的说法相悖。此外，在计算各种环境条件下和不同类型的癌症细胞中对细胞 ATP 供应的相对贡献时，发现 OxPhos 途径是糖酵解的主要 ATP 供体。因此，可以成功地利用 OxPhos 途径靶向来阻断癌细胞中依赖于 ATP 的过程，如迁移。这些观察结果可能为新的靶向治疗方法的重新设计提供指导。
