Methionine residues oxidation-reduction

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

Reduction of Ozonized Lysozyme. Methionine sulfoxide can revert to methionine with the generation of the lytic activity for photo-oxidized lysozyme (14). We tested whether the ozonized lysozyme could be reactivated by chemical reduction. The ozonized lysozyme was treated with 2-mercaptoethanol, dialysed, purified by passage through a column of Sephadex G-25 and lyoph-ilized. The product showed no increase in its lytic activity. This is not surprising because residues other than methionine are oxidized, but it may be concluded that the oxidation of methionine alone cannot account for enzyme inactivation. 

The presence of an essential tyrosine residue near the active site was suggested on the basis of experiments with tetranitromethane.54 Treatment of apotryptophanase with this reagent caused almost complete loss of catalytic activity, a great reduction of affinity for PLP and modification of about one tyrosine residue. The modified enzyme was unable to form the quinonoid intermediate with L-tryptophan or L-alanine.55 PLP protected the apoenzyme from inactivation only in the presence of activating cations (K+, NH4+, Rb+). It was shown that inactivation by tetranitromethane was not caused by oxidation of SH-groups, but partial modification of methionine (0.8 residue) was detected and might also be responsible for inactivation. It is worthy of note that modification of tryptophanase with chloramine T indicated that some methionine residues may be important for maintaining the catalytically active conformation of the enzyme.56 ... 

The function, if any, of methionine sulfoxide residues in peptides or proteins is a matter of conjecture. There is no evidence that they are of any structural significance. Indeed, since various enzymes such as ribonuclease and chymotrypsin are either partially or completely inactivated by oxidation of the methionine residues (15, 16), one hesitates to suggest any functional role for the sulfoxide. However, a role in the maintenance of oxidation-reduction potential of a biological system, as suggested by Dent (3), is conceivable. 

Methionine oxidation inducing abolition of protein function usually does not produce any changes in chemical and immunochemical properties of the protein. This infers that the oxidized protein can be reactivated again by reduction of sulfoxide residue, or may be catabolized through its regular proteolytic pathway. Facility of methionine oxidation, along with abundant production of various oxidants, enables oxidation of methionine residues. This rises a question concerning... 

This complex catalyzes the reaction through the Q cycle (Section 18.3.4). In the first half of the Q cycle, plastoquinol is oxidized to plastoquinone, one electron at a time. The electrons from plastoquinol flow through the Fe-S protein to convert oxidized plastocyanin into its reduced form. Plastocyanin is a small, soluble protein with a single copper ion bound by a cysteine residue, two histidine residues, and a methionine residue in a distorted tetrahedral arrangement (Figure 19.17). This geometry facilitates the interconversion between the Cu2+ and the Cu+ states and sets the reduction potential at an appropriate value relative to that of plastoquinol. Plastocyanin is intensely blue in color in its oxidized form, marking it as a member of the "blue copper protein," or type I copper protein family. 

The protein is completely hydrolyzed by acid (6 N HCl, 24 hours or longer at 110°C, under vacuum or inert gas) to its constituent amino acids and the resultant hydrolysate is evaporated to dryness. The amino acid composition is determined on protein hydrolysates obtained after 24,48, and 72 hours of acid treatment. The content of amino acids with bulky aliphatic side chains such as isoleucine, leucine, and valine, which undergo slow hydrolysis, is calculated from an extrapolation of the hydrolysate data to infinite time. The content of hydroxyl-containing amino acids, which are slowly destroyed during hydrolysis, is obtained by a corresponding extrapolation to zero time. Since cysteine, cystine, and methionine residues are somewhat unstable to hydrolysis, these residues are oxidized to cysteic acid and methionine sulfone, respectively, with performic acid before quantitative analysis. Cysteine, or half-cystine, is quantitated as a derivative such as carboxymethyl cysteine after reduction and alkylation, a necessary prerequisite to subsequent sequence analysis. Tryptophan... 

A reduction of the proteinase inhibitory activity is due to oxidation of the reactive methionine residue of the active center by the cigarette smoke as well as by oxygen radicals produced by leukocytes and macrophages. Emphysema is a common disease, and its most common cause is cigarette smoking. Only 1-2% of cases are due to genetic deficiency of apAT. 

The reduction of ferricytochrome c by hydrated electrons and by several free radicals has been studied by pulse radiolysis. The reduction of oxidized cytochrome c by [Fe(edta)] - follows first-order kinetics for both protein and reductant, with a rate constant of 2.57 x 10 1 mol" s" at pH 7 and activation enthalpy and entropy of 6.0 kcal mol" and —18 cal K" mol", respectively. These values are comparable to those for outer-sphere cytochrome c reductions and redox reactions involving simple iron complexes, and are compatible with outer-sphere attack of [Fe(edta)] " at the exposed haem edge, although the possibility of adjacent attack through the haem pocket is not ruled out. The rate data at pH 9 are consistent with [Fe(edta)] " reduction of two slowly interconverting forms of the protein, native kt = 2.05 X10 1 mol" S" ) and high-pH kt = 2.67 x 10 1 mol" s" ) isomers. A possible route for the transfer of the electron from Cr + to ferricytochrome c has been suggested as a result of the chemical analysis of the chromium(m) product. The reduction by Cr + of the native protein and of ferricytochrome c carboxy-methylated at the haem-linked methionine (residue 80) has been studied kinetically. At pH 6.5 the former process is simple and corresponds to a second-order rate constant of 1.21 x 10 1 mol" s". The latter, however, is complex - two chromium-... 

Oxygenation by SLO-1 is inhibited by various additives. Some of the reasons are (1) the reduction of active iron from the ferric form to the ferrous form, e,g, by N-alkylhydroxylamine [268], phenyldiazene [269], 2-benzyl-1-naphthol [270], diaryl-N-hydroxyurea [271] (2) oxidation of residues, e.g, methionine residues, by hexanal phenylhydrozone [272] (3) coordination to the active site, e.g. catechol [273], cysteine [274], hydroperoxy acids [275], chelating reagents [276], and Pt complex [277] (4) reaction with the active site, e.g. 12-iodo-ci5-9-octadecenoic acid [278]. In addition, it is reported that leukotriene A4, the electrophilic product of 5-lipoxygenases, irreversibly inactivates the enzyme [279]. 

Since cleavage is time-dependent and since tryptophan reacts rapidly with the reagent, modification without any significant cleavage was checked when the reaction was carried out with a low excess of reagent and for shorter times. This was clearly proved with staphylococcal nuclease (289). Reaction with BNPS-skatole and subsequent reduction of the 4 partially oxidized methionine residues produced a derivative of nuclease with modification only of residue 140, the single tryptophan unit. 

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... 

Reduction of Ozonized Lysozyme. The reduction of methionine sulfoxide residues of the photo-oxidized lysozyme was achieved by allowing the enzyme to react with 2-mercaptoethanol in aqueous... 

Fixed modifications are modifications to specific amino acids that are considered to be complete—i.e., every occurrence of the amino acid in the sequence is assumed to carry the modification, and the unmodified amino acid is not considered. Variable modifications, on the other hand, are incomplete, and therefore both the modified and unmodified amino acid are considered in the search. In the example discussed above, the reduction/alkylation should result in complete carbamidomethylation of all cysteine residues thus, Carbamidomethyl (C) was chosen as a fixed modification, whereas methionine oxidation, a common artifac-tual modification that is usually incomplete, was selected as a variable modification The use of multiple variable modifications will greatly reduce the significance of any match and should therefore be used with caution. 

The repair of oxidative damage may be incomplete. Only reduction of the d-diastereomer of calmodulin-bound methionine sulfoxide (L-Met-D-SO) by methionine sulfoxide reductase was demonstrated, while in the cells both d- and l-steoreoisomers are formed. Such incomplete, diastereoselective repair by methionine sulfoxide reductase contributes to the accumulation of methionine sulfoxide residues during oxidative stress and aging in vivo (S24). 

Cobalt accepts a methyl group from methyl-tetrahydrofolate, forming methyl Co +-cobalamin. Transfer of the methyl group onto homocysteine results in the formation of Co+-cobalamin, which can accept a methyl group from methyl-tetrahydrofolate to reform methyl Co +-cobalamin. However, except under strictly anaerobic conditions, demethylated Co+-cobalamin is susceptible to oxidation to Co +-cobalamin, which is catalyticaUy inactive. Reactivation of the enzyme requires reductive methylation, with S-adenosyl methionine as the methyl donor, and a flavoprotein linked to NADPH. For this reductive reactivation to occur, the dimethylbenzimidazole group of the coenzyme must be displaced from the cobalt atom by a histidine residue in the enzyme (Ludwig and Matthews, 1997). 

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