[Isotopic tracing technique in quantitative analysis of metabolic reprogramming in tumor cells]

It is hard to begin to discuss tumor metabolism without mentioning Warburg effect. Tumor metabolism has been received intensive attention in recent years for understanding Warburg effect which is also known as aerobic glycolysis. Even Warburg did not anticipate, other nutrients, such as glutamine, serine and glycine could serve as alternative source for energy demands and block building in cancer cells. To delineate altered metabolic pathways in cancer cells, isotopic tracing technique provides a novel and holistic insight in metabolic switch under control of oncogenes and tumor suppressor genes. An array of chromatography coupled with mass spectrometry is the powerful tool to detect the isotope-labeled metabolites for unlocking the underlying biochemical reactions in cancer cells. In this review article, we focus on carbon-13 and deuterium-labeling for quantitative analysis of intermediate metabolites including reduced form of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is mainly derived from pentose phosphate pathway in previous biochemical textbook. However, deuterium-isotope labeling metabolic flux analysis can reveal other important pathways for NADPH production, such as one-carbon metabolism, which is also discussed in this review.