Biliverdin and Bilirubin as Parallel Products of CO Formation

Besides the key role of heme in biology across the whole range of living things in nature, its degradation products (bilirubin and biliverdin) as well as other related linear tetrapyrroles and their derivatives play an enormous role in the regulation of various biological processes, from the simplest organisms to human beings. The primary function of HMOX enzymes is to break the cyclic tetrapyrrolic structure of heme into linear tetrapyrrole biliverdin, releasing ferrous iron and CO as additional products. The role of bilirubin in protection against increased oxidative stress has now been generally accepted, but both bilirubin and biliverdin exert a number of other biological activities with important clinical consequences. These include cell signaling functions, resulting in substantial athero-protective effects, intermediary metabolism-modulating, antiproliferative, antimutagenic, antigenotoxic, immunomodulatory, antineurodegenerative, and antiaging activities. Not only bilirubin per se, but also other tetrapyrroles used by humans and present in our environment might have therapeutic potentials.