Fig. 2

eNOS uncoupling due to BH₄ deficiency. Under conditions of oxidative stress, O₂⁻ can combine with NO yielding ONOO⁻, which strongly oxidizes BH₄ to BH₂. Decreased DHFR expression or activity prevents effective regeneration of the cofactor. BH₂ competes with BH₄ at the heme oxygenase domain but is not catalitically active, thus disturbing the normal electron flow and promoting superoxide formation