DHFR and cardiovascular disorder: Insufficient levels of GTPCH and DHFR, important enzymes in GTP and folate metabolism, respectively, have been associated with reduced BH4 availability, endothelial dysfunction and cardiovascular disease in several preclinical models (Chalupsky & Cai, 2005; Crabtree et al, 2009b, 2011; Sugiyama et al, 2009; Kidokoro et al, 2013).