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HERO ID
1229013
Reference Type
Journal Article
Title
Cystathionine gamma-lyase contributes to selenomethionine detoxification and cytosolic glutathione peroxidase biosynthesis in mouse liver
Author(s)
Okuno, T; Ueno, H; Nakamuro, K
Year
2006
Is Peer Reviewed?
Yes
Journal
Biological Trace Element Research
ISSN:
0163-4984
EISSN:
1559-0720
Volume
109
Issue
2
Page Numbers
155-171
Language
English
PMID
16444005
DOI
10.1385/BTER:109:2:155
Web of Science Id
WOS:000237495200007
Abstract
We earlier found that seleno-l-methionine (L-SeMet) as a food source of selenium (Se) is directly converted to methylselenol (CH3SeH), alpha-ketobutyrate, and ammonia by the mouse hepatic cystathionine gamma-lyase. The purpose of this study was to clarify the biological role of cystathionine gamma-lyase in Se detoxification and cytosolic glutathione peroxidase (cGPx) biosynthesis because another metabolic pathway to CH3SeH via seleno-l-cystathionine and seleno-l-cysteine (l-SeCyH) from l-SeMet has been shown by several enzymatic reactions. When mice were treated with either toxic doses of l-SeMet or a Se-deficient diet, the cystathionine gamma-lyase activity for l-SeMet was invariable, suggesting that this enzyme was effective in both detoxification and biotransformation of Se. Concerning Se biotransformation into cGPx, production of H2Se as the possible precursor was not observed by the in vitro reaction of the liver cytosol with CH3SeH. When l-SeMet was administered at the nutritional dose to mice fed a Se-deficient diet, levels of both cGPx mRNA and cGPx protein were significantly restored. This recovery was not comparatively suppressed by coadministration of periodate-oxidized adenosine, an inhibitor of S-adenosylhomocysteinase, where the conversion of l-SeMet to l-SeCyH is inhibited. However, the recovery was strongly suppressed when propargylglycine, an inhibitor of cystathionine gamma-lyase that catalyzes the alpha,gamma-elimination reaction of both l-SeMet and seleno-l-cystathionine, was treated. These results suggest that cystathionine gamma-lyase is a notable enzyme in SeMet metabolism and that CH3SeH produced by the enzymatic reaction is utilized for cGPx biosynthesis.
Keywords
L-selenomethionine; methylselenol; mouse; metabohsm; cystathionine gamma-lyase; cytosolic glutathione peroxidase
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Methanol (Non-Cancer)
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