title: Ferryl haem protonation gates peroxidatic reactivity in globins.
abstract: Ferryl (Fe(IV)=O) species are involved in key enzymatic processes with direct biomedical relevance; among others, the uncontrolled reactivities of ferryl Mb (myoglobin) and Hb (haemoglobin) have been reported to be central to the pathology of rhabdomyolysis and subarachnoid haemorrhage. Rapid-scan stopped-flow methods have been used to monitor the spectra of the ferryl species in Mb and Hb as a function of pH. The ferryl forms of both proteins display an optical transition with pK approximately 4.7, and this is assigned to protonation of the ferryl species itself. We also demonstrate for the first time a direct correlation between Hb/Mb ferryl reactivity and ferryl protonation status, simultaneously informing on chemical mechanism and toxicity and with broader biochemical implications.
authors.affiliation: Department of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK.
authors.forename: Radu
authors.initials: R
authors.lastname: Silaghi-Dumitrescu
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Reeder
authors.forename: Peter
authors.initials: P
authors.lastname: Nicholls
authors.forename: Chris E
authors.initials: CE
authors.lastname: Cooper
authors.forename: Michael T
authors.initials: MT
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D008786:Metmyoglobin / Q000737:chemistry*; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D013053:Spectrophotometry
chemical_list: D006454:Hemoglobins; D007093:Imidazoles; C517773:ferrylhemoglobin; C028048:ferrylmyoglobin; D008786:Metmyoglobin; C066317:ferryl iron; D007501:Iron; D010544:Peroxidases; D001205:Ascorbic Acid