Figure 1. Connections of Metabolic Pathways with PTM Reactions through Intermediate Metabolites and Impact of Growth Factor Signaling on Modulation of Glucose Metabolism.

(A) Diagram depicting the interplay between some of the cell metabolic pathways with some of the fundamental protein post-translational modification reactions known to modulate protein functions. DNA methylation is also included, since DNA methylation and protein methylation share the same methyl donor substrates and also the metabolites needed for demethylation. Intermediate metabolites that affect the rate of these reactions are in red. This diagram is not meant to be comprehensive, as many other metabolites can affect the rate of these reactions; however, the metabolites highlighted here are some of the best understood, and a comprehensive listing of all other metabolites is beyond the scope of this review. Stoichiometry of ATP and NADH production per molecule of glucose is omitted for simplicity. Uptake of acetate from the extracellular space is omitted for simplicity as well, but it is noteworthy that an endogenous pyruvate by keto acid dehydrogenases (such as PDH, pyruvate dehydrogenase). B-Ox, β-oxidation pathway; HBP, hexosamine biosynthesis pathway; PPP, pentode phosphate pathway; ROS, reactive oxygen species; TCA, tricarboxylic acid cycle; SAM, S-adenosyl methionine; UDP-GLcNAc, uridine diphosphate N-acetylglucosamine.

(B) A simplified generalized schematic of glycolysis upregulation by growth factor signaling, focusing on the intracellular connections between some of the major players controlling cellular metabolism, such as AKT, AMPK, ERK, mTOR, PI3K, and RAS kinases and FOXO1/3a, MYC, and HIF1α transcription factors. Glucose metabolism is profoundly affected by AKT, mTORC1, and AMPK signaling cascades, which involve the phosphorylation activation/inhibition of many enzymes and transcription factors, which then shape the cell metabolic landscape of a cell; here only major regulatory proteins were included for simplicity.