Abstract
Methionine is an essential amino acid in mammals at the junction of methylation, protein synthesis, and sulfur pathways. However, this amino acid is highly susceptible to oxidation, resulting in a mixture of methionine-S- sulfoxide and methionine-R-sulfoxide. Whether methionine is quantitatively regenerated from these compounds is unknown. Here we report that SK-Hep1 hepatocytes grew on methionine-S-sulfoxide and consumed this compound by import and methionine-S-sulfoxide reductase (MsrA)-dependent reduction, but methionine-R-sulfoxide reductases were not involved in this process, and methionine-R-sulfoxide could not be used by the cells. However, SK-Hep1 cells expressing a yeast free methionine-R-sulfoxide reductase proliferated in the presence of either sulfoxide, reduced them, and showed increased resistance to oxidative stress. Only methionine-R-sulfoxide was detected in the plasma of wild type mice, but both sulfoxides were in the plasma of MsrA knock-out mice. These results show thatmammalscan support methionine metabolism by reduction of methionine-S-sulfoxide, that this process is dependent on MsrA, that mammals are inherently deficient in the reduction of methionine-R-sulfoxide, and that expression of yeast free methionine-R-sulfoxide reductase can fully compensate for this deficiency.
| Original language | English |
|---|---|
| Pages (from-to) | 28361-28369 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 283 |
| Issue number | 42 |
| DOIs | |
| Publication status | Published - 2008 Oct 17 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Mammals reduce methionine-S-sulfoxide with MsrA and are unable to reduce methionine-R-sulfoxide, and this function can be restored with a yeast reductase. / Lee, Byung Cheon; Dung, Tien Le; Gladyshev, Vadim N.
In: Journal of Biological Chemistry, Vol. 283, No. 42, 17.10.2008, p. 28361-28369.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mammals reduce methionine-S-sulfoxide with MsrA and are unable to reduce methionine-R-sulfoxide, and this function can be restored with a yeast reductase
AU - Lee, Byung Cheon
AU - Dung, Tien Le
AU - Gladyshev, Vadim N.
PY - 2008/10/17
Y1 - 2008/10/17
N2 - Methionine is an essential amino acid in mammals at the junction of methylation, protein synthesis, and sulfur pathways. However, this amino acid is highly susceptible to oxidation, resulting in a mixture of methionine-S- sulfoxide and methionine-R-sulfoxide. Whether methionine is quantitatively regenerated from these compounds is unknown. Here we report that SK-Hep1 hepatocytes grew on methionine-S-sulfoxide and consumed this compound by import and methionine-S-sulfoxide reductase (MsrA)-dependent reduction, but methionine-R-sulfoxide reductases were not involved in this process, and methionine-R-sulfoxide could not be used by the cells. However, SK-Hep1 cells expressing a yeast free methionine-R-sulfoxide reductase proliferated in the presence of either sulfoxide, reduced them, and showed increased resistance to oxidative stress. Only methionine-R-sulfoxide was detected in the plasma of wild type mice, but both sulfoxides were in the plasma of MsrA knock-out mice. These results show thatmammalscan support methionine metabolism by reduction of methionine-S-sulfoxide, that this process is dependent on MsrA, that mammals are inherently deficient in the reduction of methionine-R-sulfoxide, and that expression of yeast free methionine-R-sulfoxide reductase can fully compensate for this deficiency.
AB - Methionine is an essential amino acid in mammals at the junction of methylation, protein synthesis, and sulfur pathways. However, this amino acid is highly susceptible to oxidation, resulting in a mixture of methionine-S- sulfoxide and methionine-R-sulfoxide. Whether methionine is quantitatively regenerated from these compounds is unknown. Here we report that SK-Hep1 hepatocytes grew on methionine-S-sulfoxide and consumed this compound by import and methionine-S-sulfoxide reductase (MsrA)-dependent reduction, but methionine-R-sulfoxide reductases were not involved in this process, and methionine-R-sulfoxide could not be used by the cells. However, SK-Hep1 cells expressing a yeast free methionine-R-sulfoxide reductase proliferated in the presence of either sulfoxide, reduced them, and showed increased resistance to oxidative stress. Only methionine-R-sulfoxide was detected in the plasma of wild type mice, but both sulfoxides were in the plasma of MsrA knock-out mice. These results show thatmammalscan support methionine metabolism by reduction of methionine-S-sulfoxide, that this process is dependent on MsrA, that mammals are inherently deficient in the reduction of methionine-R-sulfoxide, and that expression of yeast free methionine-R-sulfoxide reductase can fully compensate for this deficiency.
UR - http://www.scopus.com/inward/record.url?scp=57649119783&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57649119783&partnerID=8YFLogxK
U2 - 10.1074/jbc.M805059200
DO - 10.1074/jbc.M805059200
M3 - Article
C2 - 18697736
AN - SCOPUS:57649119783
VL - 283
SP - 28361
EP - 28369
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 42
ER -