Document Detail


Screening of toxicity biomarkers for methionine excess in rats.
MedLine Citation:
PMID:  16702345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although many animal studies have reported that dietary excess of methionine causes toxic changes including growth suppression and hemolytic anemia, the biochemical mechanism and biomarkers for methionine toxicity have not been well elucidated. The present study aimed to identify toxicity biomarkers from plasma metabolites in rats fed excessive methionine. Young growing rats were fed graded doses of additional methionine for 2 wk. Cluster analysis of multivariate correlations was performed on the physiological and toxicity variables with plasma metabolites detected by GC/MS, amino acid analyzer, and thiol-specific analysis. Indicative variables for hemolysis such as splenic nonheme iron content and plasma bilirubin were grouped in the same cluster as many methionine metabolites. Homocysteine and some undefined metabolites in this cluster were found to be strong discriminators between nontoxic and toxic levels of methionine intake. Product-to-precursor ratios of each methionine metabolite demonstrated that excessive methionine intake caused a marked decrease only in the ratio of cystathionine to homocysteine, suggesting that metabolism from homocysteine to cystathionine would be rate limiting in the disposal of excessive methionine. Collectively from these results, homocysteine appeared to be the most plausible biomarker to assess methionine excess as a surrogate marker both for toxicity and for setting a metabolic upper limit.
Authors:
Sakino Toue; Riho Kodama; Michiko Amao; Yasuko Kawamata; Takeshi Kimura; Ryosei Sakai
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of nutrition     Volume:  136     ISSN:  0022-3166     ISO Abbreviation:  J. Nutr.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-16     Completed Date:  2006-07-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1716S-1721S     Citation Subset:  IM    
Affiliation:
Ajinomoto Co., Inc., Institute of Life Sciences, Kawasaki, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / blood
Analysis of Variance
Animals
Bilirubin / blood
Biological Markers / blood*
Cystathionine / blood
Diet
Gas Chromatography-Mass Spectrometry
Glycine / administration & dosage
Hemolysis
Homocysteine / blood
Iron / blood,  metabolism
Male
Methionine / administration & dosage,  toxicity*
Rats
Rats, Inbred F344
Serine / administration & dosage
Spleen / metabolism
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Biological Markers; 454-28-4/Homocysteine; 56-40-6/Glycine; 56-45-1/Serine; 56-88-2/Cystathionine; 63-68-3/Methionine; 635-65-4/Bilirubin; 7439-89-6/Iron

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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