Molecular model for α-globin function in the MEJ. In the presence of O₂, Fe²⁺ α-globin bound to eNOS degrades NO by dioxygenation, thereby enhancing vascular tone. eNOS and/or CYB5R3/CYB5A can reduce Fe³⁺ α-globin to the Fe²⁺ state to support another round of dioxygenation. Alternatively, under oxidizing conditions, Fe³⁺ α-globin may be released from eNOS and bind α-hemoglobin stabilizing protein (AHSP) to form a stable complex that cannot catalyze dioxygenation. When reducing conditions are restored, CYB5R3/CYB5A or eNOS can convert AHSP-bound Fe³⁺ α-globin to the Fe²⁺ form, which favors its transfer to eNOS for continued NO scavenging. During hypoxia, deoxy-Fe²⁺ α-globin can reduce NO₂⁻ to generate NO, thereby enhancing vasodilation. The figure was created using BioRender.