a The Division of Interventional Radiology, Russell H. Morgan Department of Radiology & Radiological Science , The Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Crit Rev Biochem Mol Biol. 2018 Dec;53(6):667-682. doi: 10.1080/10409238.2018.1556578. Epub 2019 Jan 22.
Aerobic glycolysis is the process of oxidation of glucose into pyruvate followed by lactate production under normoxic condition. Distinctive from its anaerobic counterpart (i.e. glycolysis that occurs under hypoxia), aerobic glycolysis is frequently witnessed in cancers, popularly known as the "Warburg effect", and it is one of the earliest known evidences of metabolic alteration in neoplasms. Intracellularly, aerobic glycolysis circumvents mitochondrial oxidative phosphorylation (OxPhos), facilitating an increased rate of glucose hydrolysis. This in turn enables cancer cells to successfully compete with normal cells for glucose uptake in order to maintain uninterrupted growth. In addition, evading OxPhos mitigates excessive generation/accumulation of reactive oxygen species that otherwise may be deleterious to cells. Emerging data indicate that aerobic glycolysis in cancer also promotes glutaminolysis to satisfy the precursor requirements of certain biosynthetic processes (e.g. nucleic acids). Next, the metabolic intermediates of aerobic glycolysis also feed the pentose phosphate pathway (PPP) to facilitate macromolecular biosynthesis necessary for cancer cell growth and proliferation. Extracellularly, the extrusion of the end-product of aerobic glycolysis, i.e. lactate, alters the tumor microenvironment, and impacts cancer-associated cells. Collectively, accumulating data unequivocally demonstrate that aerobic glycolysis implicates myriad of molecular and functional processes to support cancer progression. This review, in the light of recent research, dissects the molecular intricacies of its regulation, and also deliberates the emerging paradigms to target aerobic glycolysis in cancer therapy.
有氧糖酵解是指在正常氧条件下，葡萄糖氧化为丙酮酸，随后生成乳酸的过程。与无氧糖酵解（即在缺氧条件下发生的糖酵解）不同，有氧糖酵解在癌症中经常被观察到，通常被称为“瓦博格效应”，它是肿瘤代谢改变最早被认识的证据之一。在细胞内，有氧糖酵解绕过线粒体氧化磷酸化（OxPhos），促进葡萄糖水解速率增加。这反过来使癌细胞能够成功与正常细胞竞争葡萄糖摄取，以维持不间断的生长。此外，逃避 OxPhos 减轻了活性氧（ROS）的过度产生/积累，否则可能对细胞有害。新出现的数据表明，癌细胞中的有氧糖酵解还促进谷氨酰胺分解代谢，以满足某些生物合成过程（如核酸）的前体需求。接下来，有氧糖酵解的代谢中间产物也为戊糖磷酸途径（PPP）提供燃料，以促进癌细胞生长和增殖所需的大分子生物合成。在细胞外，有氧糖酵解的终产物乳酸的排出改变了肿瘤微环境，并影响与癌症相关的细胞。总之，越来越多的数据明确表明，有氧糖酵解涉及多种分子和功能过程，以支持癌症进展。这篇综述根据最近的研究，剖析了其调控的分子复杂性，并讨论了靶向癌症治疗中有氧糖酵解的新范例。
