Methionine sulfoxide

Last updated
Methionine sulfoxide
Methionine sulfoxide.png
Names
IUPAC name
2-Amino-4-(methylsulfinyl)butanoic acid
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.057.891 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • ±:263-700-7
PubChem CID
UNII
  • InChI=1S/C5H11NO3S/c1-10(9)3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)
    Key: QEFRNWWLZKMPFJ-UHFFFAOYSA-N
  • ±:InChI=1/C5H11NO3S/c1-10(9)3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)
    Key: QEFRNWWLZKMPFJ-UHFFFAOYAN
  • ±:O=C(O)C(N)CCS(=O)C
Properties
C5H11NO3S
Molar mass 165.21 g·mol−1
Appearancewhite solid
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H315, H319, H335
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Methionine sulfoxide is the organic compound with the formula CH3S(O)CH2CH2CH(NH2)CO2H. It is an amino acid that occurs naturally although it is formed post-translationally.

Contents

Oxidation of the sulfur of methionine results in methionine sulfoxide or methionine sulfone. The sulfur-containing amino acids methionine and cysteine are more easily oxidized than the other amino acids. [1] [2] Unlike oxidation of other amino acids, the oxidation of methionine can be reversed by enzymatic action, specifically by enzymes in the methionine sulfoxide reductase family of enzymes. The three known methionine sulfoxide reductases are MsrA, MsrB, and fRmsr. [2] Oxidation of methionine results in a mixture of the two diastereomers methionine-S-sulfoxide and methionine-R-sulfoxide, which are reduced by MsrA and MsrB, respectively. [3] MsrA can reduce both free and protein-based methionine-S-sulfoxide, whereas MsrB is specific for protein-based methionine-R-sulfoxide. fRmsr, however, catalyzes the reduction of free methionine-R-sulfoxide. [2] Thioredoxin serves to recycle by reduction some of the methionine sulfoxide reductase family of enzymes, whereas others can be reduced by metallothionein. [4]

Biochemical function

Methionine sulfoxide (MetO), the oxidized form of the amino acid methionine (Met), increases with age in body tissues, which is believed by some to contribute to biological ageing. [5] [6] Oxidation of methionine residues in tissue proteins can cause them to misfold or otherwise render them dysfunctional. [5] Uniquely, the methionine sulfoxide reductase (Msr) group of enzymes act with thioredoxin to catalyze the enzymatic reduction and repair of oxidized methionine residues. [5] Moreover, levels of methionine sulfoxide reductase A (MsrA) decline in aging tissues in mice and in association with age-related disease in humans. [5] There is thus a rationale for thinking that by maintaining the structure, increased levels or activity of MsrA might retard the rate of aging.

Indeed, transgenic Drosophila (fruit flies) that overexpress methionine sulfoxide reductase show extended lifespan. [7] However, the effects of MsrA overexpression in mice were ambiguous. [8] MsrA is found in both the cytosol and the energy-producing mitochondria, where most of the body's endogenous free radicals are produced. Transgenically increasing the levels of MsrA in either the cytosol or the mitochondria had no significant effect on lifespan assessed by most standard statistical tests, and may possibly have led to early deaths in the cytosol-specific mice, although the survival curves appeared to suggest a slight increase in maximum (90%) survivorship, as did analysis using Boschloo's Exact test, a binomial test designed to test greater extreme variation. [8]

The oxidation of methionine serves as a switch that deactivates certain protein activities such as E.coli ribosomal protein, L12. [9] Proteins with great amount of methionine residues tend to exist within the lipid bilayer as methionine is one of the most hydrophobic amino acids. Those methionine residues that are exposed to the aqueous exterior thus are vulnerable to oxidation. The oxidized residues tend to be arrayed around the active site and may guard access to this site by reactive oxygen species. Once oxidized, the MetO residues are reduced back to methionine by the enzyme methionine sulfoxide reductase. Thus, an oxidation–reduction cycle occurs in which exposed methionine residues are oxidized (e.g., by H2O2) to methionine sulfoxide residues, which are subsequently reduced. [10]

Methionine(protein)+ H2O2→ Methionine Sulfoxide(protein)+ H2O

Methionine Sulfoxide(protein)+ NADPH+H+→ Methionine(protein)+ NADP++H2O

See also

Related Research Articles

<span class="mw-page-title-main">Selenocysteine</span> Chemical compound

Selenocysteine is the 21st proteinogenic amino acid. Selenoproteins contain selenocysteine residues. Selenocysteine is an analogue of the more common cysteine with selenium in place of the sulfur.

<span class="mw-page-title-main">Cysteine</span> Proteinogenic amino acid

Cysteine is a semiessential proteinogenic amino acid with the formula HOOC−CH(−NH2)−CH2−SH. The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. Cysteine is chiral, only L-cysteine is found in nature.

<span class="mw-page-title-main">Methionine</span> Sulfur-containing amino acid

Methionine is an essential amino acid in humans.

<span class="mw-page-title-main">Ribonucleotide reductase</span> Class of enzymes

Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase (rNDP), is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of the ribose ring of nucleoside diphosphates. This reduction produces deoxyribonucleotides. Deoxyribonucleotides in turn are used in the synthesis of DNA. The reaction catalyzed by RNR is strictly conserved in all living organisms. Furthermore, RNR plays a critical role in regulating the total rate of DNA synthesis so that DNA to cell mass is maintained at a constant ratio during cell division and DNA repair. A somewhat unusual feature of the RNR enzyme is that it catalyzes a reaction that proceeds via a free radical mechanism of action. The substrates for RNR are ADP, GDP, CDP and UDP. dTDP is synthesized by another enzyme from dTMP.

<span class="mw-page-title-main">Methionine synthase</span> Mammalian protein found in Homo sapiens

Methionine synthase also known as MS, MeSe, MTR is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms part of the S-adenosylmethionine (SAMe) biosynthesis and regeneration cycle, and is the enzyme responsible for linking the cycle to one-carbon metabolism via the folate cycle. There are two primary forms of this enzyme, the Vitamin B12 (cobalamin)-dependent (MetH) and independent (MetE) forms, although minimal core methionine synthases that do not fit cleanly into either category have also been described in some anaerobic bacteria. The two dominant forms of the enzymes appear to be evolutionary independent and rely on considerably different chemical mechanisms. Mammals and other higher eukaryotes express only the cobalamin-dependent form. In contrast, the distribution of the two forms in Archaeplastida (plants and algae) is more complex. Plants exclusively possess the cobalamin-independent form, while algae have either one of the two, depending on species. Many different microorganisms express both the cobalamin-dependent and cobalamin-independent forms.

Nitrite reductase refers to any of several classes of enzymes that catalyze the reduction of nitrite. There are two classes of NIR's. A multi haem enzyme reduces NO2− to a variety of products. Copper containing enzymes carry out a single electron transfer to produce nitric oxide.

<span class="mw-page-title-main">Sulfur assimilation</span> Incorporation of sulfur into living organisms

Sulfur assimilation is the process by which living organisms incorporate sulfur into their biological molecules. In plants, sulfate is absorbed by the roots and then be transported to the chloroplasts by the transipration stream where the sulfur are reduced to sulfide with the help of a series of enzymatic reactions. Furthermore, the reduced sulfur is incorporated into cysteine, an amino acid that is a precursor to many other sulfur-containing compounds. In animals, sulfur assimilation occurs primarily through the diet, as animals cannot produce sulfur-containing compounds directly. Sulfur is incorporated into amino acids such as cysteine and methionine, which are used to build proteins and other important molecules. Besides, With the rapid development of economy, the increase emission of sulfur results in environmental issues, such as acid rain and hydrogen sulfilde.

<span class="mw-page-title-main">Glutaredoxin</span>

Glutaredoxins are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. In humans this oxidation repair enzyme is also known to participate in many cellular functions, including redox signaling and regulation of glucose metabolism. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to thioredoxins, which are reduced by thioredoxin reductase, no oxidoreductase exists that specifically reduces glutaredoxins. Instead, glutaredoxins are reduced by the oxidation of glutathione. Reduced glutathione is then regenerated by glutathione reductase. Together these components compose the glutathione system.

<span class="mw-page-title-main">Peroxiredoxin</span> Family of antioxidant enzymes

Peroxiredoxins are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels and thereby mediate signal transduction in mammalian cells. The family members in humans are PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, and PRDX6. The physiological importance of peroxiredoxins is indicated by their relative abundance. Their function is the reduction of peroxides, specifically hydrogen peroxide, alkyl hydroperoxides, and peroxynitrite.

In enzymology, a L-methionine (R)-S-oxide reductase (EC 1.8.4.14) is an enzyme that catalyzes the chemical reaction

In enzymology, a L-methionine (S)-S-oxide reductase (EC 1.8.4.13) is an enzyme that catalyzes the chemical reaction

In enzymology, a peptide-methionine (R)-S-oxide reductase (EC 1.8.4.12) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">MSRA (gene)</span> Protein-coding gene in the species Homo sapiens

Peptide methionine sulfoxide reductase (Msr) is a family of enzymes that in humans is encoded by the MSRA gene.

<span class="mw-page-title-main">MSRB2</span> Protein-coding gene in the species Homo sapiens

Methionine-R-sulfoxide reductase B2, mitochondrial is an enzyme that in humans is encoded by the MSRB2 gene. The MRSB2 enzyme catalyzes the reduction of methionine sulfoxide to methionine.

<span class="mw-page-title-main">SEPX1</span> Protein-coding gene in the species Homo sapiens

Methionine-R-sulfoxide reductase B1 is an enzyme that in humans is encoded by the SEPX1 gene.

Sulfur is metabolized by all organisms, from bacteria and archaea to plants and animals. Sulfur can have an oxidation state from -2 to +6 and is reduced or oxidized by a diverse range of organisms. The element is present in proteins, sulfate esters of polysaccharides, steroids, phenols, and sulfur-containing coenzymes.

Methionine-S-oxide reductase (EC 1.8.4.5, methyl sulfoxide reductase I and II, acetylmethionine sulfoxide reductase, methionine sulfoxide reductase, L-methionine:oxidized-thioredoxin S-oxidoreductase) is an enzyme with systematic name L-methionine:thioredoxin-disulfide S-oxidoreductase. This enzyme catalyses the following chemical reaction

Peptide-methionine (S)-S-oxide reductase (EC 1.8.4.11, MsrA, methionine sulphoxide reductase A, methionine S-oxide reductase (S-form oxidizing), methionine sulfoxide reductase A, peptide methionine sulfoxide reductase, formerly protein-methionine-S-oxide reductase) is an enzyme with systematic name peptide-L-methionine:thioredoxin-disulfide S-oxidoreductase (L-methionine (S)-S-oxide-forming). This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Nickel superoxide dismutase</span>

Nickel superoxide dismutase (Ni-SOD) is a metalloenzyme that, like the other superoxide dismutases, protects cells from oxidative damage by catalyzing the disproportionation of the cytotoxic superoxide radical to hydrogen peroxide and molecular oxygen. Superoxide is a reactive oxygen species that is produced in large amounts during photosynthesis and aerobic cellular respiration. The equation for the disproportionation of superoxide is shown below:

Dr. Herbert Weissbach NAS NAI AAM is an American biochemist/molecular biologist.

References

  1. ↑ Bin, P; Huang, R; Zhou, X (2017). "Oxidation Resistance of the Sulfur Amino Acids: Methionine and Cysteine". BioMed Research International. 2017: 9584932. doi: 10.1155/2017/9584932 . PMC   5763110 . PMID   29445748.
  2. 1 2 3 Lee BC, Dikiy A, Kim HY, Gladyshev VN (2009). "Functions and evolution of selenoprotein methionine sulfoxide reductases". Biochimica et Biophysica Acta (BBA) - General Subjects. 1790 (11): 1471–1477. doi:10.1016/j.bbagen.2009.04.014. PMC   3062201 . PMID   19406207.
  3. ↑ Kim HY, Gladyshev VN (2004). "Methionine sulfoxide reduction in mammals: characterization of methionine-R-sulfoxide reductases". Molecular Biology of the Cell. 15 (3): 1055–1064. doi:10.1091/mbc.E03-08-0629. PMC   363075 . PMID   14699060.
  4. ↑ Sagher D, Brunell D, Hejtmancik JF, Kantorow M, Brot N, Weissbach H (2006). "Thionein can serve as a reducing agent for the methionine sulfoxide reductases". Proceedings of the National Academy of Sciences of the United States of America . 103 (23): 8656–8661. Bibcode:2006PNAS..103.8656S. doi: 10.1073/pnas.0602826103 . PMC   1592241 . PMID   16735467.
  5. 1 2 3 4 Stadtman ER, Van Remmen H, Richardson A, Wehr NB, Levine RL (2005). "Methionine oxidation and aging". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1703 (2): 135–140. doi:10.1016/j.bbapap.2004.08.010. PMID   15680221.
  6. ↑ Shringarpure R, Davies KJ (2002). "Protein turnover by the proteasome in aging and disease". Free Radical Biology & Medicine. 32 (11): 1084–1089. doi:10.1016/S0891-5849(02)00824-9. PMID   12031893.
  7. ↑ Ruan H, Tang XD, Chen ML, Joiner ML, Sun G, Brot N, Weissbach H, Heinemann SH, Iverson L, Wu CF, Hoshi T (2002). "High-quality life extension by the enzyme peptide methionine sulfoxide reductase". Proceedings of the National Academy of Sciences of the United States of America . 99 (5): 2748–2753. Bibcode:2002PNAS...99.2748R. doi: 10.1073/pnas.032671199 . PMC   122419 . PMID   11867705.
  8. 1 2 Salmon AB, Kim G, Liu C, Wren JD, Georgescu C, Richardson A, Levine RL (December 2016). "Effects of transgenic methionine sulfoxide reductase A (MsrA) expression on lifespan and age-dependent changes in metabolic function in mice". Redox Biol. 10: 251–256. doi:10.1016/j.redox.2016.10.012. PMC   5099276 . PMID   27821326.
  9. ↑ Brot, N; Weissbach, L; Werth, J; Weissbach, H (April 1981). "Enzymatic reduction of protein-bound methionine sulfoxide". Proceedings of the National Academy of Sciences of the United States of America. 78 (4): 2155–8. Bibcode:1981PNAS...78.2155B. doi: 10.1073/pnas.78.4.2155 . PMC   319302 . PMID   7017726.
  10. ↑ Levine, RL; Mosoni, L; Berlett, BS; Stadtman, ER (Dec 24, 1996). "Methionine residues as endogenous antioxidants in proteins". Proceedings of the National Academy of Sciences of the United States of America. 93 (26): 15036–40. Bibcode:1996PNAS...9315036L. doi: 10.1073/pnas.93.26.15036 . PMC   26351 . PMID   8986759.
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