Figure 1.

Regulatory mechanisms for the expression and activity of HO enzymes. Heme oxygenase 1 (HO-1) is induced by transcription factors, such as Nrf2 and AP-1, as schematically shown in the figure. Heme oxygenase 2 (HO-2) binds to Fe²⁺ ion of the heme group through cysteine residues in the heme regulation motifs (HRMs) of the enzyme, inducing its activity (up-arrow). Additionally, phosphorylation of serine 79 residue enhances the enzymatic activity (up-arrow). In addition, nitrosylation of the cysteine residue inhibits enzyme activity (down-arrow). Both isoforms catalyze the oxidation of the heme group producing Fe²⁺, CO, and biliverdin (BV).