Peptide methionine sulfoxide reductase (Msr) is a family of

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 that in humans is encoded by the ''MSRA''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

Msr is ubiquitous and highly conserved. Human and animal studies have shown the highest levels of expression in kidney and liver. It carries out the enzymatic reduction of

methionine sulfoxide 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. Redox, Oxidation of the sulfur of methionine results in methionine sulf ...

(MetO), the oxidized form of the amino acid

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 ...

(Met), back to methionine, using thioredoxin to catalyze the enzymatic reduction and repair of oxidized methionine residues. Its proposed function is thus the repair of oxidative damage to proteins to restore biological activity. Oxidation of methionine residues in tissue proteins can cause them to misfold or otherwise render them dysfunctional.

Clinical significance

MetO increases with age in body tissues, which is believed by some to contribute to biological ageing. 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 structureincreased 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 test Boschloo's test is a statistical hypothesis test for analysing 2x2 contingency tables. It examines the association of two Bernoulli distributed random variables and is a uniformly more powerful alternative to Fisher's exact test. It was proposed ...

, 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. Deletion of this gene has been associated with

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

resistance in mice, while overexpression reduces insulin resistance in old mice.

Function

Clinical significance

See also

References

Further reading