Source:http://linkedlifedata.com/resource/pubmed/id/19616616
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2009-9-23
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pubmed:abstractText |
Lipoic acid is a disulfhydryl-containing compound used in clinical medicine and in experimental models as an antioxidant. We developed a stable isotope dilution capillary gas chromatography/mass spectrometry assay for lipoic acid. We assayed a panel of the metabolites of transmethylation and transsulfuration 30 min after injecting 100 mg/kg lipoic acid in a rat model. Lipoic acid values rose 1000-fold in serum and 10-fold in liver. A methylated metabolite of lipoic acid was also detected but not quantitated. Lipoic acid injection caused a massive increase in serum S-adenosylhomocysteine and marked depletion of liver S-adenosylmethionine. Serum total cysteine was depleted but liver cysteine and glutathione were maintained. Serum total homocysteine doubled, with increases also in cystathionine, N,N-dimethylglycine, and alpha-aminobutyric acid. In contrast, after injection of 2-mercaptoethane sulfonic acid, serum total cysteine and homocysteine were markedly depleted and there were no effects on serum S-adenosylmethionine or S-adenosylhomocysteine. We conclude that large doses of lipoic acid displace sulfhydryls from binding sites, resulting in depletion of serum cysteine, but also pose a methylation burden with severe depletion of liver S-adenosylmethionine and massive release of S-adenosylhomocysteine. These changes may have previously unrecognized deleterious effects that should be investigated in both human disease and experimental models.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/AG-09834,
http://linkedlifedata.com/resource/pubmed/grant/R01 AG009834-14,
http://linkedlifedata.com/resource/pubmed/grant/R01 AG009834-15,
http://linkedlifedata.com/resource/pubmed/grant/U45 ES-015678,
http://linkedlifedata.com/resource/pubmed/grant/U54 ES015678-010001
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/S-Adenosylhomocysteine,
http://linkedlifedata.com/resource/pubmed/chemical/S-Adenosylmethionine,
http://linkedlifedata.com/resource/pubmed/chemical/Thioctic Acid
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1873-4596
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1147-53
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:19616616-Animals,
pubmed-meshheading:19616616-Antioxidants,
pubmed-meshheading:19616616-Cysteine,
pubmed-meshheading:19616616-Gas Chromatography-Mass Spectrometry,
pubmed-meshheading:19616616-Liver,
pubmed-meshheading:19616616-Male,
pubmed-meshheading:19616616-Methylation,
pubmed-meshheading:19616616-Rats,
pubmed-meshheading:19616616-Rats, Sprague-Dawley,
pubmed-meshheading:19616616-S-Adenosylhomocysteine,
pubmed-meshheading:19616616-S-Adenosylmethionine,
pubmed-meshheading:19616616-Thioctic Acid
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pubmed:year |
2009
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pubmed:articleTitle |
Alpha-lipoic acid induces elevated S-adenosylhomocysteine and depletes S-adenosylmethionine.
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pubmed:affiliation |
Department of Medicine and Division of Hematology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA. Sally.Stabler@ucdenver.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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