2-Deoxyglucose: an anticancer and antiviral therapeutic, but not any more a low glucose mimetic

2-Deoxyglucose (2-DG), a non-metabolizable glucose analogue, blocks glycolysis and inhibits protein glycosylation. It has been tested in multiple studies for possible application as an anticancer or antiviral therapeutic. The inhibitory effect of 2-DG on ATP generation made it a good candidate molecule as a calorie restriction mimetic as well. Furthermore, 2-DG has been utilized in numerous studies to simulate a condition of glucose starvation. Because 2-DG disrupts glucose metabolism, protein glycosylation, and ER quality control at the same time, a cellular or pathologic outcome could be easily misinterpreted without clear understanding of 2-DG's effect on each of these aspects. However, the effect of 2-DG on protein glycosylation has rarely been investigated. A recent study suggested that 2-DG causes hyperGlcNAcylation of proteins, while low glucose supply causes hypoGlcNAcylation. In certain aspects of cellular physiology, this difference could be disregarded, but in others, this may possibly cause totally different outcomes.