| Evaluation of a screening method by liquid chromatography-tandem mass spectrometry for estimating effect of drugs on the activation and β-oxidation of fatty acids in mitochondria. | |
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MedLine Citation:
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PMID: 21054395 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Fatty acid metabolism is controlled not only by the acyl-coenzyme A (CoA) synthetases but by some enzymes in the β-oxidation cycle. Medium-chain and long-chain acyl-CoA esters are key metabolites in fatty acid metabolism. We have developed an enzymatic assay method for determining chain shortening of the acyl-CoAs via β-oxidation from palmitic and octanoic acids in liver mitochondria. We have evaluated the assay method for detecting whether drugs influence the activation or the β-oxidation of fatty acids. METHODS: Liver mitochondria were used for investigating the effect of drugs on fatty acid metabolism. The drugs selected were salicylic acid, diclofenac, valproic acid and paracetamol. Each acyl-CoA formed was analysed by liquid chromatography-tandem mass spectrometry. KEY FINDINGS: After less than 5 min of incubation, the levels of acyl-CoAs reflected the acyl-CoA synthetase activity, whereas after 60-min incubation they reflected the activity of some enzymes in the β-oxidation cycle. Salicylic acid, diclofenac and valproic acid inhibited the medium-chain acyl-CoA synthetases, whereas valproic acid only exhibited a weak inhibitory activity toward the β-oxidation of the medium-chain fatty acids. In the case of long-chain fatty acid metabolism, salicylic acid and diclofenac inhibited both the activation and β-oxidation, whereas valproic acid was a weak inhibitor for only the β-oxidation activity. Paracetamol showed hardly any influence on the metabolism of medium-chain and long-chain fatty acids. CONCLUSIONS: These findings suggest that salicylic acid, diclofenac, valproic acid and paracetamol exert a different influence on fatty acid metabolism depending on the length of the acyl chain. This assay allows sensitive and selective analysis for predicting the pathways by which drugs exert a greater influence over fatty acid metabolism. |
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Authors:
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Fumiyo Kasuya; Ryota Nishizawa; Teiichi Masuyama; Maya Kazumi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-04 |
Journal Detail:
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Title: The Journal of pharmacy and pharmacology Volume: 62 ISSN: 2042-7158 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-08 Completed Date: 2011-05-11 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 0376363 Medline TA: J Pharm Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1697-703 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain. |
Affiliation:
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Biochemical Toxicology Laboratory, Faculty of Pharmaceutical Sciences, Kobegakuin University, Kobe, Japan. kasuya@pharm.kobegakuin.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetaminophen
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pharmacology Analgesics, Non-Narcotic / pharmacology Animals Anti-Infective Agents / pharmacology Anti-Inflammatory Agents, Non-Steroidal / analysis, pharmacology Chromatography, Liquid / methods Coenzyme A Ligases / antagonists & inhibitors, metabolism Diclofenac / metabolism, pharmacology Enzyme Inhibitors / pharmacology Fatty Acids / antagonists & inhibitors, metabolism*, pharmacology Lipid Metabolism / drug effects* Male Mice Mice, Mutant Strains Mitochondria, Liver / drug effects, enzymology, metabolism* Oxidation-Reduction Salicylic Acid / pharmacology Tandem Mass Spectrometry / methods Valproic Acid / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Non-Narcotic; 0/Anti-Infective Agents; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Enzyme Inhibitors; 0/Fatty Acids; 103-90-2/Acetaminophen; 15307-86-5/Diclofenac; 69-72-7/Salicylic Acid; 99-66-1/Valproic Acid; EC 6.2.1.-/Coenzyme A Ligases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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