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. 2019 Jun 26;9:52. doi: 10.1186/s13578-019-0317-8

Fig. 1.

Fig. 1

PKM2: Junction of Metabolic Networks and Signal Cascades. POST-Warburg effect, in glucose metabolism, tumor cells divide glucose metabolism into three separate parts of glycolysis, tricarboxylic acid cycle and oxidative phosphorylation (OXPHOS). The effect of PKM2 is currently considered to be the interception of glucose metabolism and the metabolic pathway is transferred to the pentose phosphate pathway (PPP), the uronic acid pathway (UAP), the polyol pathway (PYP), etc. for the synthesis of the subsequent five-carbon ribose and non-essential amino acids. The TCA circle is backed up by fatty acid metabolism and amino acid metabolism, and its main purpose is to provide raw materials for the synthesis of non-essential amino acids, and the secondary purpose is to supply REDOX equivalents [43]. Although the classic glutathione replenishment pathway is well known. But there are more similar pathways in tumor cells which marked with blue text in the picture. PKM2 can be replenished by many amino acids such as alanine (Ala), cysteine (Cys), glycine (Gly), threonine (Thr), tryptophan (Try), etc. Although Ac-CoA mainly relies on fatty acid metabolism for supply, it can also be replenished by some amino acids such as leucine, isoleucine, tryptophan etc. The tricarboxylic acid cycle (TCA) serves as the focal point for the metabolism of the three major metabolic processes, the amino acid is also the most abundant in its form of replenishment. For example, a variety of amino acids such as aspartic acid, arginine, glutamic acid, glutamine, histidine, isoleucine, methionine, phenylalanine, proline, tyrosine, threonine, valine etc. can complement the eight intermediate metabolites in the tricarboxylic acid cycle (TCA). In the three major metabolic processes, the REDOX equivalents produced will converge in the mitochondria and eventually promote the oxidative phosphorylation (OXPHOS) of the electron transport chain, while protecting the mitochondrial function of the tumor cells, also providing the cells with a large amount of adenosine triphosphate (ATP) required for survival as well [44]. REDOX equivalents marked with purple text in the picture