| Methionine-deficient diet induces post-transcriptional downregulation of cystathionine β-synthase. | |
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MedLine Citation:
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PMID: 20036517 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Baiqing Tang; Aladdin Mustafa; Sapna Gupta; Stepan Melnyk; S Jill James; Warren D Kruger |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-12-29 |
Journal Detail:
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Title: Nutrition (Burbank, Los Angeles County, Calif.) Volume: 26 ISSN: 1873-1244 ISO Abbreviation: Nutrition Publication Date: 2010 Nov-Dec |
Date Detail:
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Created Date: 2010-10-18 Completed Date: 2011-02-22 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 8802712 Medline TA: Nutrition Country: United States |
Other Details:
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Languages: eng Pagination: 1170-5 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Cancer Genetics and Signaling Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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CA06927/CA/NCI NIH HHS; HL57299/HL/NHLBI NIH HHS; R01 HL057299-12/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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