In breast cancer, the oncogene phosphoglycerate dehydrogenase (PHGDH) was reportedly able to accumulate both S/R-2HG enantiomers from α-KG [120] as well as the overexpression of the mitochondrial hydroxyacid-oxoacid-transhydrogenase (HOT), which produces R-2HG as a consequence of the 4- hydroxybutyrate to succinic semialdehyde conversion [121,122] (Figure 1). Here, ADHFE1 is linked to breast carcinoma.