Recent developments in intermediary metabolic research show us that our understanding of intermediary metabolism is not even nearly close to completion.Acetylation is emerging as a major regulatory mechanism for metabolism,joining the well-known mechanisms of transcriptional regulation,feedback inhibition,allosteric regulation and phosphorylation.Direct and indirect evidence has shown that acetylation of metabolic enzymes causes various changes,ranging from inhibiting and activating catalytic activity to affecting protein stability.Acetylation may also play a universal role in coordinating enzyme activity within a pathway,or metabolic flux among pathways.Another finding that has put intermediary metabolism into focus is that certain metabolites play indispensable roles in cell signaling.Unbalanced accumulation of 2-hydroxylglutarate or decrease in α-ketoglutarate significantly affects a family of proteins called dioxygenases,alters tumor-related hypoxia-inducible factor pathways,and is possibly involved in histone methylation.These new observations have raised broad interest in the scientific community,due to the close connections between metabolism and human diseases.
