Document Detail


Methionine-deficient diet induces post-transcriptional downregulation of cystathionine β-synthase.
MedLine Citation:
PMID:  20036517     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Elevated plasma total homocysteine (tHcy) is a risk factor for a variety of human diseases. Homocysteine is formed from methionine and has two primary metabolic fates: remethylation to form methionine or commitment to the transsulfuration pathway by the action of cystathionine β-synthase (CBS). We have examined the metabolic response in mice of a shift from a methionine-replete to a methionine-free diet.
METHODS AND RESULTS: We found that shifting 3-mo-old C57BL6 mice to a methionine-free diet caused a transient increase in tHcy and an increase in the tHcy/methionine ratio. Because CBS is a key regulator of tHcy, we examined CBS protein levels and found that within 3 d on the methionine-deficient diet, animals had a 50% reduction in the levels of liver CBS protein and enzyme activity. Examination of CBS mRNA and studies of transgenic animals that express CBS from a heterologous promoter indicated that this reduction is occurring post-transcriptionally. Loss of CBS protein was unrelated to intracellular levels of S-adenosylmethionine, a known regulator of CBS activity and stability.
CONCLUSION: Our results imply that methionine deprivation induces a metabolic state in which methionine is effectively conserved in tissue by shutdown of the transsulfuration pathway by an S-adenosylmethionine-independent mechanism that signals a rapid downregulation of CBS protein.
Authors:
Baiqing Tang; Aladdin Mustafa; Sapna Gupta; Stepan Melnyk; S Jill James; Warren D Kruger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-12-29
Journal Detail:
Title:  Nutrition (Burbank, Los Angeles County, Calif.)     Volume:  26     ISSN:  1873-1244     ISO Abbreviation:  Nutrition     Publication Date:    2010 Nov-Dec
Date Detail:
Created Date:  2010-10-18     Completed Date:  2011-02-22     Revised Date:  2011-11-01    
Medline Journal Info:
Nlm Unique ID:  8802712     Medline TA:  Nutrition     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1170-5     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Cancer Genetics and Signaling Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Animals
Cystathionine beta-Synthase / genetics,  metabolism*
Deficiency Diseases / blood,  enzymology
Diet / adverse effects*
Down-Regulation*
Female
Homeostasis
Homocysteine / blood
Liver / enzymology,  metabolism
Methionine / administration & dosage*,  blood,  deficiency*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Polymerase Chain Reaction
RNA, Messenger / metabolism
S-Adenosylmethionine / metabolism
Time Factors
Grant Support
ID/Acronym/Agency:
CA06927/CA/NCI NIH HHS; HL57299/HL/NHLBI NIH HHS; R01 HL057299-12/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 29908-03-0/S-Adenosylmethionine; 454-28-4/Homocysteine; 63-68-3/Methionine; EC 4.2.1.22/Cystathionine beta-Synthase

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


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