Methionine sulphoxide residues

McLafferty rearrangement 133, 163 Meisenheimer complexes 699, 702 Metal-chelated intermediates 838 Metal-halogen exchange 781, 784 Methionine, oxidation of 852-855 Methionine sulphone 853 Methionine sulphoxide 851-869 reduction of 1063 residues of... 

Alpha-l-antiprotease (ai-AP) limits tissue damage arising from the actions of the leucocyte protease, elastase (Carrell and Travis, 1985), and there is much evidence available for the oxidative inactivation of this protein by oxygen-derived free-radical species and hypochlorous acid/hypochlorite anion (HOCl/OCP). The mechanism of this inactivation appears to involve the oxidation of a critical methionine residue (Met-358) to its corresponding sulphoxide and methionine sulphoxide has been detected in ai-AP samples isolated from the lungs of cigarette smokers (Carp et al., 1982) and rheumatoid synovial fluids (Wong and Travis, 1980). 

Pulmonary emphysema is associated with cigarette smoking in normal individuals, as well as with ajAT deficiency. In smokers, though absolute levels of aiAT are normal, elastase inhibitory activity is depressed [93]. This is due to the oxidation of a critical, reactive centre, methionine residue (met 358) to methionine sulphoxide [94], Likewise, a large proportion of aiAT is also inactivated in the rheumatoid joint cavity [95,96], even when synovial fluid samples are analysed immediately after aspiration [97]. Again,... 

Previously, we have examined the formation of amino acid hydroperoxides following exposure to different radical species [100]. We observed that valine was most easily oxidised, but leucine and lysine are also prone to this modification in free solution. Scheme 12 illustrates the mechanism for formation of valine hydroperoxide. However, tertiary structure becomes an important predictor in proteins, where the hydrophobic residues are protected from bulk aqueous radicals, and lysine hydroperoxides are most readily oxidised. Hydroperoxide yield is poor from Fenton-derived oxidants as they are rapidly broken down in the presence of metal ions [101]. Like methionine sulphoxide, hydroperoxides are also subject to repair, in this case via glutathione peroxidase. They can also be effectively reduced to hydroxides, a reaction supported by the addition of hydroxyl radical in the presence of oxygen. Extensive characterisation of the three isomeric forms of valine and leucine hydroxides has been undertaken by Fu et al. [102,103], and therefore will not be discussed further here. 

Oxidation of methionine residues of food proteins and nutritional availability of methionine sulphoxide. Food Chem. 3 85... 

The answer may lie in the fact that methionine is very sensitive to oxidation, and apPI which has been oxidized at this centre (a,-PI J is both a much less potent (Kj = 1.5 x 10 M) and slower acting (kassoc = 3.1 x 10 M" s ) inhibitor of HLE [45, 46], This decrease in activity can be rationalized by the fact that oxidation of the methionine sulphur to a sulphoxide increases the size and polarity of the P,-substituent. The increase in size may directly interfere with fitting this residue into the Spsubsite of HLE, and the change in polarity may cause a reduction in the net binding energy gained by the transition from a purely aqueous solution to a bound environment. 

It has been reported that a single methionine residue of rabbit reticulocyte 15-lipoxygenase can be oxidized to its sulphoxide by treatment of the enzyme with 13-hydroperoxy-octadecadienoic acid (a 15-lipoxygenase product from linoleic acid) under anaerobic conditions [59]. Since under this condition the enzyme functioned as lipohydroperoxidase , splitting the hydroperoxide, and resulted in self-inactivation , a central role of the methionine residue was presumed for the catalysis of the enzyme. Recently, this particular methionine has been identified as Met-590 in human 15-lipoxygenase and as Met-591 in rabbit 15-lipoxygenase. When Met-590 in the human enzyme is replaced by leucine by the site-directed mutagenesis, the mutant enzyme is still inactivated by 13-hydroperoxyoctadeca-dienoic acid, 15-HpETE or AA. The result shows that the enzyme inactivation is not attributable to methionine oxidation [60]. 

The oxidation of the methionine residue in a protected hexapeptide to the sulphoxide has been reported to occiu merely by aerial oxidation when AcOH is used as solvent. Methionine itself, and other sulphides of... 

Protein-quinone reactions seem to have little influence on protein digestibility or on the bioavailability of tryptophan. Methionine does not appear to react covalently but may be extensively oxidized to its sulphoxide with some reduction in bioavailability. The reactions of cysteine were not investigated in our study because of the low level of cyst(e)ine in casein. Pierpoint (1969ab) has reported that cysteine reacts like lysine via a substitution into the quinone ring and it is also possible that cyst(e)ine residues may be oxidized (Finley and Lundin, 1980). 

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