Effects of folic acid and vitamin B12 supplementation on Kynureninase expression. (A) In a non-pathological scenario, Kynu is possibly expressed at normal levels, as well as the repressor protein, which does not have sufficient levels to completely suppress Kynu expression. (B) In a pathological scenario, this repressor may have a hypomethylated promoter region, leading to continuous expression and increased protein levels, resulting in intense Kynu repression. KYNU can process 3-hydroxykynurenine (3-HK), and low levels of this enzyme may trigger the accumulation of 3-HK, resulting in a toxic effect due to the generation of free radical superoxide and hydrogen peroxide, which leads to cell death. (C) With folic acid and B12 supplementation, the DNA methylation process is normalized, and the repressor’s promoter region returns to its standard methylation state or becomes completely methylated, reducing or silencing the expression of this repressor and allowing for Kynu expression to occur and 3-HK to be appropriately processed.