Regulation of ROS Production and Vascular Function by Carbon Monoxide
Figure 1
The heme degradation pathway and roles of its byproducts in the production of angiogenic modulators. (a) Reaction intermediates in the heme oxygenase-catalyzed oxidation of heme to biliverdin. The substituents on porphyrin are vinyl (V), methyl (M), and propionate (P). The -, -, -, and -meso positions are labeled. The HO reaction consists of three oxidation steps and initiates with the formation of the heme-HO complex. Next, heme is reduced to the state by the electron donated from NADPH, and this step produces CO by the region-specific cleavage of the porphyrin ring of heme at the -meso carbon atom. The final step is binding to verdoheme, which produces and biliverdin. Biliverdin is converted by biliverdin reductase to bilirubin. (b) Potential proangiogenic effects of heme-degraded products such as CO, biliverdin/bilirubin and . These products possess potential proangiogenic effects by inducing proangiogenic mediators or by antagonizing antiangiogenic factors.
