Methionine sulfoxide is the

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

with the formula CH₃S(O)CH₂CH₂CH(NH₂)CO₂H. It is an

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

that occurs naturally although it is formed post-translationally.

Oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

of the

sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...

results in methionine sulfoxide or methionine sulfone. The sulfur-containing amino acids methionine and

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

are more easily oxidized than the other amino acids. Unlike oxidation of other amino acids, the oxidation of methionine can be reversed by enzymatic action, specifically by

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s in the methionine sulfoxide reductase family of enzymes. The three known methionine sulfoxide reductases are MsrA, MsrB, and fRmsr. Oxidation of methionine results in a mixture of the two

diastereomer In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have dif ...

s methionine-S-sulfoxide and methionine-R-sulfoxide, which are reduced by MsrA and MsrB, respectively. 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.

Thioredoxin Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, thioredoxins are encoded by ''TXN'' and ''TXN2'' genes. Loss-of-func ...

serves to recycle by reduction some of the methionine sulfoxide reductase family of enzymes, whereas others can be reduced by

metallothionein Metallothionein (MT) is a family of cysteine-rich, low molecular weight (MW ranging from 500 to 14000 Da) proteins. They are localized to the membrane of the Golgi apparatus. MTs have the capacity to bind both physiological (such as zinc, copp ...

Biochemical function

Methionine sulfoxide (MetO), the oxidized form of the amino acid

(Met), increases with age in body tissues, which is believed by some to contribute to biological ageing. Oxidation of methionine residues in tissue proteins can cause them to misfold or otherwise render them dysfunctional. Uniquely, the methionine sulfoxide reductase (Msr) group of enzymes act with

thioredoxin Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, thioredoxins are encoded by ''TXN'' and ''TXN2'' genes. Loss-of-func ...

to catalyze the enzymatic reduction and repair of oxidized methionine residues. Moreover, levels of methionine sulfoxide reductase A (MsrA) decline in aging tissues in mice and in association with age-related disease in humans. 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 ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

(fruit flies) that overexpress methionine sulfoxide reductase show extended lifespan. However, the effects of MsrA overexpression in mice were ambiguous. MsrA is found in both the cytosol and the energy-producing

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

, where most of the body's endogenous

free radicals In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spont ...

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 In statistics, the binomial test is an exact test of the statistical significance of deviations from a theoretically expected distribution of observations into two categories using sample data. Usage The binomial test is useful to test hypoth ...

designed to test greater extreme variation. The oxidation of methionine serves as a switch that deactivates certain protein activities such as E.coli ribosomal protein, L12. 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. Methionine(protein)+ H₂O₂→ Methionine Sulfoxide(protein)+ H₂O Methionine Sulfoxide(protein)+ NADPH+H⁺→ Methionine(protein)+ NADP⁺+H₂O

References

{{Reflist

External links

Methionine oxidation chemistry
Biochemistry Organic redox reactions Amino acid derivatives

Biochemical function

See also

References

External links