Porphyrin Traps Its Terminator! Concerted and Stepwise Porphyrin Degradation Mechanisms Induced by Heme-Oxygenase and Cytochrome P450

摘要

The enzyme heme-oxygenase (HO) traps heme species and induces their degradation. The degradation process (Scheme 1) is thought to serve three key functions: a) maintenance of iron homeostasis, b) creation of CO in the brain that acts as a neurotransmitter akin to NO, and c) generation of products (e.g., biliverdin) that play a role in the defense mechanism against oxidative stress. Structural studies by Poulos and co-workers of the human form (hHO-1) of the enzyme-heme complex show that the trapped heme undergoes ligation by an imidazole ring of a histidine side chain and a water molecule. Upon dioxygen uptake, followed by two-electron reduction and protonation, which activate the O=O bond, the heme unit undergoes hydroxylation at the α-meso position and subsequently opens up, releasing iron and carbon monoxide.