Amino acid free radicals in oxidised metmyoglobin

King, N. Kelso; Looney, F.D.; Winfield, ME

doi:10.1016/0005-2795(67)90039-6

Cited by 97 publications

(6 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relative concentrations of the singlet (metHb Ͼ SW metMb Ͼ HH metMb) are maintained over the whole time course. We have reported before that the low, nonstoichiometric absolute concentration of the radicals often observed in such systems (Kelso King and Winfield, 1963;Kelso King et al, 1967) is a result of a pseudo-steady state, where the rates of radical formation and decay are both H 2 O 2 concentration dependent (Svistunenko et al, 1997b). The lineshape of the singlet is essentially unchanged over the pH range 6 -8 (illustrated for metHb in Fig.…”

Section: Resultsmentioning

confidence: 89%

“…The assignment of the singlet to a particular molecular structure is difficult because of the absence of any hyperfine structure or g-factor anisotropy. Comparisons with radicals generated from purified amino acids were equivocal, suggesting that phenylalanine, histidine, or tyrosine could all contribute to the observed spectrum (Kelso King et al, 1967).…”

Section: Introductionmentioning

confidence: 99%

“…This one electron oxidation takes place along with H 2 O 2 reduction to water, the latter being a two-electron process. The second electron, participating in H 2 O 2 reduction, comes from the protein's globin, leaving it in the free radical state (Gibson and Ingram, 1956;Gibson et al, 1958;Kelso King et al, 1967;Kelso King and Winfield, 1963):…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative Study of Tyrosine Radicals in Hemoglobin and Myoglobins Treated with Hydrogen Peroxide

Svistunenko

Dunne

Fryer

et al. 2002

Biophysical Journal

View full text Add to dashboard Cite

The reactions of hydrogen peroxide with human methemoglobin, sperm whale metmyoglobin, and horse heart metmyoglobin were studied by electron paramagnetic resonance (EPR) spectroscopy at 10 K and room temperature. The singlet EPR signal, one of the three signals seen in these systems at 10 K, is characterized by a poorly resolved, but still detectable, hyperfine structure that can be used to assign it to a tyrosyl radical. The singlet is detectable as a quintet at room temperature in methemoglobin with identical spectral features to those of the well characterized tyrosyl radical in photosystem II. Hyperfine splitting constants found for Tyr radicals were used to find the rotation angle of the phenoxyl group. Analysis of these angles in the crystal structures suggests that the radical resides on Tyr151 in sperm whale myoglobin, Tyr133 in soybean leghemoglobin, and either alphaTyr42, betaTyr35, or betaTyr130 in hemoglobin. In the sperm whale metmyoglobin Tyr103Phe mutant, there is no detectable tyrosyl radical present. Yet the rotation angle of Tyr103 (134 degrees) is too large to account for the observed EPR spectrum in the wild type. Tyr103 is the closest to the heme. We suggest that Tyr103 is the initial site of the radical, which then rapidly migrates to Tyr151.

show abstract

Section: Resultsmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Study of Tyrosine Radicals in Hemoglobin and Myoglobins Treated with Hydrogen Peroxide

Svistunenko

Dunne

Fryer

et al. 2002

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…4) LOO• + * LH → LOOH + * L• As the formation of ferryl heme requires removal of one electron from ferric heme, and as reduction of H 2 O 2 to water requires two electrons, a second electron comes from oxidizing the protein. This results, at least in part, in the formation of a free radical located on an amino acid residue of the globin (P •+ ) [9][10][11]. Subsequent migration and deprotonation of this cation radical yields a neutral radical (often termed R • ) that can be observed by EPR spectroscopy [12,13].…”

Section: The Redox and Radical Chemistry Of Myoglobin And Hemoglobinmentioning

confidence: 99%

Hemoglobin and Myoglobin Associated Oxidative Stress: from Molecular Mechanisms to Disease States

Reeder¹,

Wilson

2005

CMC

151

111

View full text Add to dashboard Cite

The heme based respiratory proteins myoglobin and hemoglobin can, under certain conditions, exhibit a peroxidase-like enzymic activity, in which a catalytic cycle, driven by peroxides, leads to oxidation of bio molecules. These heme proteins are implicated in what is termed "oxidative stress" as this catalytic cycle, when it occurs in vivo, generates cytotoxic product that are implicated in the pathology of a number of disease states. Here we review the evidence that such reactions occur in vivo, in particular in animal models and human patients and examine the underlying chemical mechanism. This mechanism involves the production of ferryl heme (Fe(IV)=O(2-)) and it is this and associated radicals that initiate processes such as lipid peroxidation and the generation of bioactive molecules such as isoprostanes. The reactivity of the high oxidation state of the heme also allows us to identify unambiguous biomarkers for its presence in vivo in such conditions as rhabdomyolysis and brain hemorrhage. Ways to inhibit the peroxidatic cycle are discussed and the role of iron chelators such as desferrioxamine is discussed in terms of their often neglected properties as reducing agents. Suppression of the peroxidatic activity of hemoglobin is discussed in the context of the development of blood substitutes.

show abstract

“…Following the observation that mice lacking the gene to produce Mb had no obvious change in phenotype other than ‘white’ muscle (Godecke et al 1999), the physiological role of Mb was reassessed, and it is now considered also to be an intracellular scavenger of nitric oxide, protecting NO‐sensitive respiratory enzymes such as cytochrome c oxidase (Eich et al 1996; Brunori, 2001), as follows:

For over a century, it has been known that Mb and Hb can also react with peroxides (Kobert, 1900), inducing complex redox chemical reactions. Hydrogen peroxide oxidizes the ferrous protein to generate the ferryl state and, in the case of the reaction with ferric protein, a protein‐based cation radical (Mb· + ; Kelso‐King et al 1967), as follows:

The ferryl protein is equivalent to peroxidase compound II and the ferryl plus radical equivalent to peroxidase compound I. Unlike classical peroxidases, in which the radical on the porphyrin or a nearby amino acid residue is stable, the radical formed on Mb or Hb quickly migrates away from the haem group, formally an electron transfer to the initial radical cation yielding a radical cation on another amino acid residue.…”

Section: The Enzymatic Activity Of Myoglobin and Haemoglobin Under Pamentioning

confidence: 99%

Oxygen‐binding haem proteins

Wilson

Reeder

2007

Experimental Physiology

View full text Add to dashboard Cite

Myoglobin and haemoglobin, the respiratory pigments of mammals and some molluscs, annelids and arthropods, belong to an ancient superfamily of haem-associated globin proteins. Members of this family share common structural and spectral features. They also share some general functional characteristics, such as the ability to bind ligands, e.g. O 2 , CO and NO, at the iron atom and to undergo redox changes. These properties are used in vivo to perform a wide range of biochemical and physiological roles. While it is acknowledged that the major role of haemoglobin is to bind oxygen reversibly and deliver it to the tissues, this is not its only function, while the often-stated role of myoglobin as an oxygen storage protein is possibly a misconception. Furthermore, haemoglobin and myoglobin express enzymic activities that are important to their function, e.g. NO dioxygenase activity or peroxidatic activity that may be partly responsible for pathophysiology following haemorrhage. Evidence for these functions is described, and the discussion extended to include proteins that have recently been discovered and that are expressed at low levels within the cell. These proteins are hexaco-ordinate, unlike haemoglobin and myoglobin, and are widely distributed throughout the animal kingdom (e.g. neuroglobins and cytoglobins). They may have specialist roles in oxygen delivery to particular sites within the cell but may also perform roles associated with O 2 sensing and signalling and in responses to stress, e.g. protection from reactive oxygen and nitrogen species. Haemoglobins are also widespread in plants and bacteria and may serve similar protective functions.

show abstract

Amino acid free radicals in oxidised metmyoglobin

Cited by 97 publications

References 16 publications

Comparative Study of Tyrosine Radicals in Hemoglobin and Myoglobins Treated with Hydrogen Peroxide

Comparative Study of Tyrosine Radicals in Hemoglobin and Myoglobins Treated with Hydrogen Peroxide

Hemoglobin and Myoglobin Associated Oxidative Stress: from Molecular Mechanisms to Disease States

Oxygen‐binding haem proteins

Contact Info

Product

Resources

About