Figure 4.

The AR impacts one-carbon metabolism and downstream processes by modulating the expression of specific associated enzymes. Green and red arrows/lines indicate reactions that are respectively activated and repressed by the AR via the modulation of enzyme expression. Enzymes include ODC1 (involved in polyamine synthesis), GNMT (catalyzes the conversion of glycine to sarcosine) and CBS (involved in glutathione synthesis). Metabolites increased and decreased by the AR in this manner are indicated in green and red, respectively. Black color depicts the one-carbon metabolism pathways and some other metabolites derived from it. Cellular processes potentially affected by AR-mediated one-carbon metabolism modulation are indicated in blue. By inhibiting AR, ADT (grey box) likely blocks many of these metabolic alterations in PCa cells, thus producing potentially beneficial and deleterious effects as discussed in the text.