The electrochemical oxidation of methionine on glassy carbon or boron doped electrodes at physiological pH occurs at a potential higher than + 1V while tyrosine or tryptophan, for example, is oxidized at 0.65 V. Considering this differences in oxidation potentials, why is methionine in vivo readily oxidized?
Nevertheless, the reduction of methionine sulfoxide into methionine by methionine sulfoxide reductases is the only reversible system (regarding the amino acids oxidation) and it has been postulated that this serves as a catalytic antioxidant mechanism against deleterious effects of oxidative stress on proteins.
Another example is the Amyloid beta –Cu2+ complex. There are many evidences that Cu2+ is binds to histidine residues at position 6, 13 and 14 and is reduced by methionine 35 residue. The reduction potential of Cu2+ is around -0.1 V whereas the oxidation potential of methionine is higher than +1 V. Since the difference is more than -1V why does this occurs?
Not all methionine(s) containing proteins are oxidized in vivo...in proteomics Met-oxidation occurs usually during sample preparation or digestion...you need to analyze the Met source if protein or peptide and minimize the handling time before your measurement. Good Luck !
I agree with this fact: Not all methionine(s) containing proteins are oxidized in vivo.
The question is why methionine is oxidized (in some cases) prior to another amino acids. Why in literature met is described as readily oxidized when electrochemical measurements show that is the hardest oxidizable amino acid?
It is possible a decrease of standard potential of met as a result of intermolecular interactions inside peptide chain?
I don't know the 100% exact answer for your question but if I may dare to speculate this effect might be due to solvation. In fact, all two electron oxidations should proceed in a way that the extraction of second electron from a molecule is more difficult. This is always true for vacuum (first and second ionization potentials). However, every electrochemist encountered that CV of reversible two-electron process in solution may proceed in a whole spectrum of cases from two independent electron transfers upto single two-electron transfer CV characterised by 29 mV peak separation. In this case, extraction of the second electron is easier than extraction of the first one. The reversal of the is due to differences in solvation energies between first and second oxidised states of the molecule. Thus, the solvation may shift the potential magnificiently. In proteins, tertiary structure is a delicate interplay between hydrophobic - hydrophilic forces and local solvation can be different throughout protein methionine sites.
The resolution of this problem from the electrochemical perspective is complicated, with a couple of exceptions, by the fact that methionine oxidation is irreversible. However, using a series of model compounds, we have been able to establish a correlation between peak potentials corresponding to the two-electron oxidation of aliphatic thioethers, charge transfer complexes absorbance maxima, and ionization potentials determined by photoelectron spectroscopy. (Coleman, BR, et al., Adv. Chem. Ser.,1982, 417-441. In addition there are a number of papers dealing with the radical intermediates that can be characterized by pulse radiolysis. This work is being extended to electron-hopping across peptide networks (Glass, RS et al., J. Am Chem. Soc, 2009,131:13791-13805) The short answer to the question is that ease of thioether oxidation depends upon the existence of a proximal electron-rich group such as a carboxylate, OH group, or unapaired electrons that might be found in other sulfur-containing derivatives or nitrogen. The effect of neighboring group participation in the oxidation is significant. In proteins if a methionine sulfur is proximal to any of these groups, they are mosre susceptible to oxidation. In addition there can be hot spots created by the formation of metal complex (Fe-HIS, for example) that can promote the formation of reactive oxygen species via Fenton-type reactions. Thioether oxidation probably occurs most of the time through inner-sphere electron transfer.
Sorry for the late reply, but I think this may help answer the question you're looking for.
PHOTO-OXIDATION, SENSITIZED BY PROFLAVINE, OF A NUMBER OF PROTEIN CONSTITUENTS L. A. AE. SLUYTERMAN Philips Research Laboratories, N.V. Philips' Gloeilampenfabrieken, Eindhoven (The Netherlands)
The same logic that is used in the paper can also be applied with cysteine since it must be ionized prior to oxidation as well.
In short: Cysteine's pKa for it's thiol is above pH 8 (so it does not readily oxidize below this pH). Tyrosine's pKa for the ionizable phenolic group is 10 (so it does not readily oxidize below this pH), and Histidine require a pH of about 7 to oxidize. Methionine and Tryptophan are neutral, and thus their oxidations are not limited by pH. Thus from the pH range of 0-5, usually oxidation is predominantly Methionine and Tryptophan, and by pH of 7, it becomes Methionine, Tryptophan, and Histidine. This is a big chunk of the pH scale, and thus, may constitute why Methionine and Tryptophan are always considered oxidized first (there is no requirement for ionization).
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