Methionine sensor

Bigelow, D. J., and Squier, T. C. 2005. Redox modulation of cellular signaling and metabolism through reversible oxidation of methionine sensors in calcium regulatory proteins. Biochim. Biophys. Acta 1703 121-134. 

Muratore C, Power-charnitsky V, Deth RC. 2006. Cell-specific differences in methionine synthase at the mRNA level A role for methionine synthase as a sensor of oxidative stress. Society for Neuroscience Abstract Viewer and Itinerary Planner 81.9. 

As illustrated in Fig. 1, methionine synthase is positioned at the intersection between transsulfuration and methylation pathways. As a consequence, its level of activity exerts control over cellular redox status, since it determines the proportion of HCY that will be diverted toward cysteine and GSH synthesis. Methionine synthase activity is exceptionally sensitive to inhibition during oxidative stress, primarily because its cobalamin cofactor is easily oxidized (Liptak and Brunold, 2006). This allows methionine synthase to serve as a redox sensor, lowering its activity whenever the level of oxidation increases, until increased GSH synthesis brings the system back into balance. Electrophilic compounds, such as oxygen-containing xenobiotic metabolites, also react with cobalamin, inactivating the enzyme and increasing diversion of HCY toward GSH synthesis (Watson et al., 2004). Thus, methionine synthase is a sensor of both redox and xenobiotic status. 

Methionine synthase is composed of five structural domains that provide for binding of its substrate HCY, the methyl donor 5-methyItetrahydrofolate, cobal-amin, and SAM (Fig. 4). In most tissues SAM is utilized to methylate oxidized cobalamin, in conjunction with electron donation by methionine synthase reductase, thereby restoring methylcobalamin and allowing resumption of activity. This mode of reactivation is required approximately every 100-1,000 turnovers, even under strictly anaerobic laboratory conditions (Bandarian et al., 2003). Under physiological conditions, oxidation of cobalamin is undoubtedly much more common, illustrating how vitamin B12 serves as a sensor of redox status. During oxidative stress, cobalamin is more frequently oxidized and more HCY is diverted toward cysteine and GSH synthesis. 

The following substrates can be determined with almost identical sensitivity by using D-amino acid oxidase in combination with an ammonium ion sensitive electrode D-alanine, D-leucine, D-norleucine, D-methionine, and D-phenylalanine. L-amino acid oxidase sensors have been described for L-leucine, L-cysteine, L-methionine, L-tryptophan, and L-tyrosine (Guilbault and Hrabankova, 1971), and L-histidine and L-arginine (Tran-Minh and Broun, 1975). 

Yao and Wasa (1988a) assembled modified electrodes for amino acids by crosslinking L- or D-amino acid oxidase with glutaraldehyde on silanized platinum probes. The sensors were employed as detectors in high pressure liquid chromatography. Whereas the L-amino acid oxidase electrode responded to L-tyrosine, L-leucine, L-methionine, and L-phenylalanine in amounts as low as 2 pmoles, the D-amino acid electrode measured only D-methionine and D-tyrosine. The response time in steady state measurements was only 5-10 s. 

A modified electrode using a functionalized triazole polymer film may serve as electrochemical sensor for L-methionine [89]. There, a glassy carbon electrode is modified with an electropolymerized film of 3-amino-5-mercapto-l,2,4-triazole. The sensor works at physiological pH. L-Methionine is an essential amino acid which occurs in human blood plasma, serum, and urine. An abnormal concentration of L-Methionine may cause coronary artery disease. 

Revin SB, John SA. Selective and sensitive electrochemical sensor for 1-methionine at physiological ph using functionalized triazole polymer film modified electrode. Electroanalysis 2012 24(6) 1277-83. 

Specific sensors for phenylalanine, tyrosine, glutamine, lysine, and methionine have been described in the literature. 

Severin etal recently pnblished another successful array for differentiating peptides by employing three commercially available metal complexes (27-29). One complex contained rhodium, one ruthenium, and one palladium. In the presence of six selected fluorophores, these constituents formed a collection of differential sensors. The receptors were able to differentiate 10 dipeptides at a 50 pM concentration (the closed symbols in Figure 9) and 2 dipeptides at 20 pM concentration (the open symbols in Figure 9). The authors found that peptides containing histidine and methionine residues were best discriminated, most likely because these residues displaced a larger fraction of... 

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