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Review
. 2011 Jan 15;50(2):221-7.
doi: 10.1016/j.freeradbiomed.2010.11.008. Epub 2010 Nov 11.

The biological significance of methionine sulfoxide stereochemistry

Byung Cheon Lee  1 , Vadim N Gladyshev
Affiliations
Review

The biological significance of methionine sulfoxide stereochemistry

Byung Cheon Lee et al. Free Radic Biol Med. .

Abstract

Methionine can be oxidized by reactive oxygen species to a mixture of two diastereomers, methionine-S-sulfoxide and methionine-R-sulfoxide. Both free amino acid and protein-based forms of methionine-S-sulfoxide are stereospecifically reduced by MsrA, whereas the reduction of methionine-R-sulfoxide requires two enzymes, MsrB and fRMsr, which act on its protein-based and free amino acid forms, respectively. However, mammals lack fRMsr and are characterized by deficiency in the reduction of free methionine-R-sulfoxide. The biological significance of such biased reduction of methionine sulfoxide has not been fully explored. MsrA and MsrB activities decrease during aging, leading to accumulation of protein-based and free amino acid forms of methionine sulfoxide. Since methionine is an indispensible amino acid in human nutrition and a key metabolite in sulfur, methylation, and transsulfuration pathways, the consequences of accumulation of its oxidized forms require further studies. Finally, in addition to methionine, methylsulfinyl groups are present in various drugs and natural compounds, and their differential reduction by Msrs may have important therapeutic implications.

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Figures

Figure 1
Figure 1
Oxidation of Met. ROS can oxidize Met to two diastereomers of Met sulfoxide, Met-S-SO and Met-R-SO.
Figure 2
Figure 2
Reduction of methionine sulfoxides by three classes of Msr. Protein-based Met-S-SO and Met-R-SO are reduced by MsrA and MsrB, respectively, whereas free Met-S-SO and free Met-R-SO are reduced by MsrA and fRMsr. MsrBs can also contribute to the reduction of free Met-R-SO, but with low efficiency.
Figure 3
Figure 3
Pathways of Met utilization. The overall Met metabolism can be subdivided into two systems: the methionine/methylation cycle, and the transsulfuration pathway. In addition, cysteine utilization depends on Met. The subject of this review is reversible Met oxidation that so far received little attention with regard to regulating Met fluxes.
Figure 4
Figure 4
Methylsulfinyl-containing drugs and compounds.
See this image and copyright information in PMC

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