Methionine sulfoxide reductase contributes to meeting dietary methionine requirements

Laboratory of Biochemistry, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
Archives of Biochemistry and Biophysics (Impact Factor: 3.02). 04/2012; 522(1):37-43. DOI: 10.1016/
Source: PubMed


Methionine sulfoxide reductases are present in all aerobic organisms. They contribute to antioxidant defenses by reducing methionine sulfoxide in proteins back to methionine. However, the actual in vivo roles of these reductases are not well defined. Since methionine is an essential amino acid in mammals, we hypothesized that methionine sulfoxide reductases may provide a portion of the dietary methionine requirement by recycling methionine sulfoxide. We used a classical bioassay, the growth of weanling mice fed diets varying in methionine, and applied it to mice genetically engineered to alter the levels of methionine sulfoxide reductase A or B1. Mice of all genotypes were growth retarded when raised on chow containing 0.10% methionine instead of the standard 0.45% methionine. Retardation was significantly greater in knockout mice lacking both reductases. We conclude that the methionine sulfoxide reductases can provide methionine for growth in mice with limited intake of methionine, such as may occur in the wild.

Download full-text


Available from: Rodney Levine, Aug 27, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Significance: Selenium is utilized in the methionine sulfoxide reduction system that occurs in most organisms. Methionine sulfoxide reductases (Msrs), MsrA and MsrB, are the enzymes responsible for this system. Msrs repair oxidatively damaged proteins, protect against oxidative stress, and regulate protein function, and have also been implicated in the aging process. Selenoprotein forms of Msrs containing selenocysteine (Sec) at the catalytic site are found in bacteria, algae, and animals. Recent advances: A selenoprotein MsrB1 knockout mouse has been developed. Significant progress in the biochemistry of Msrs has been made, which includes findings of a novel reducing system for Msrs and of an interesting reason for the use of Sec in the Msr system. The effects of mammalian MsrBs, including selenoprotein MsrB1 on fruit fly aging, have been investigated. Furthermore, it is evident that Msrs are involved in methionine metabolism and regulation of the trans-sulfuration pathway. Critical issues: This article presents recent progress in the Msr field while focusing on the physiological roles of mammalian Msrs, functions of selenoprotein forms of Msrs, and their biochemistry. Future directions: A deeper understanding of the roles of Msrs in redox signaling, the aging process, and metabolism will be achieved. The identity of selenoproteome of Msrs will be sought along with characterization of the identified selenoprotein forms. Exploring new cellular targets and new functions of Msrs is also warranted.
    No preview · Article · Dec 2012 · Antioxidants & Redox Signaling
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glucosinolates from the genus Brassica can be converted into bioactive compounds known to induce phase II enzymes which may decrease the risk of cancers. Conversion via hydrolysis is usually by the brassica enzyme myrosinase which can be inactivated by cooking or storage. We examined the potential of three beneficial bacteria, Lactobacillus plantarum KW30, Lactococcus lactis subsp. lactis KF147, Escherichia coli Nissle 1917, and known myrosinase-producer Enterobacter cloacae, to catalyse the conversion of glucosinolates in broccoli extract. Enterobacteriaceae consumed on average 65% glucoiberin and 78% glucoraphanin, transforming them into glucoiberverin and glucoerucin respectively and small amounts of iberverin nitrile and erucin nitrile. The lactic acid bacteria did not accumulate reduced glucosinolates consuming all at 30-33% and transforming these into iberverin nitrile, erucin nitrile, sulforaphane nitrile and further unidentified metabolites. Adding beneficial bacteria to a glucosinolate rich diet may increase glucosinolate transformation thereby increasing host exposure to bioactives.
    Full-text · Article · Mar 2013 · Journal of Agricultural and Food Chemistry
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AeNAT5 (NCBI, ABZ81822), an orphan member of the insect-specific Nutrient Amino acid Transporter subfamily of SoLute Carrier family 6 (NAT-SLC6) and the first representative of a novel eukaryotic methionine-selective transport system (M), was cloned from cDNA of the vector mosquito, Aedes aegypti. It has orphan orthologs throughout several mosquito genomes, but not in Drosophila or outside Diptera. It shows the highest apparent affinity to L-Met (K0.5 = 0.021 mM) and its metabolites Homocysteine and Cysteine (K0.5 = 0.89 and 2.16 mM), but weakly interact with other substrates. It has a Na+ - coupled mechanism (K0.5 Na+ ~ 46 mM) with 1AA:1Na+ stoichiometry that maintains ~ 60% activity in Cl- - free media. In situ hybridization showed accumulation of AeNAT5 transcript in the absorptive and secretory epithelia, as well as in specific peripheral neurons and the central ganglia of mosquito larvae. The labeling pattern is distinct from that of the previously characterized AeNAT1. RNAi of AeNAT5 increases larval mortality during ecdysis and dramatically suppresses adult emergence. Our results showed that in addition to previously characterized broad spectra and aromatic amino acid selective transport systems, the mosquito NAT-SLC6 subfamily evolved a unique mechanism for selective absorption of sulfur-containing substrates. We demonstrated specific patterns of alimentary and neuronal transcription of AeNAT5 in mosquito larvae that is collateral with the indispensable function of this transporter in mosquito development.
    Full-text · Article · May 2013 · Insect Biochemistry and Molecular Biology
Show more