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Nevertheless, NNMT overexpression is likely to disrupt the balance between NAD + synthesis and breakdown and decrease NAD + -dependent enzyme activity ( via NNMT and 1-MNA ( + levels and SIRT3 activity, downregulating the expression of genes involved in fatty acid oxidation ( Figure 2 Disruption of Methyl Donor Balance in NNMT Overexpression Cancer Cells NNMT is also a key node in methyl donor metabolism