Document Detail


Triheptanoin--a medium chain triglyceride with odd chain fatty acids: a new anaplerotic anticonvulsant treatment?
MedLine Citation:
PMID:  21855298     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The triglyceride of heptanoate (C7 fatty acid), triheptanoin, is a tasteless oil used to treat rare metabolic disorders in USA and France. Heptanoate is metabolized by β-oxidation to provide propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis - the refilling of the tricarboxylic acid cycle. Heptanoate is also metabolized by the liver to the C5 ketones, β-ketopentanoate and/or β-hydroxypentanoate, which are released into the blood and thought to enter the brain via monocarboxylate transporters. Oral triheptanoin has recently been discovered to be reproducibly anticonvulsant in acute and chronic mouse seizures models. However, current knowledge on alterations of brain metabolism after triheptanoin administration and anaplerosis via propionyl-CoA carboxylation in the brain is limited. This review outlines triheptanoin's unique anticonvulsant profile and its clinical potential for the treatment of medically refractory epilepsy. Anaplerosis as a therapeutic approach for the treatment of epilepsy is discussed. More research is needed to elucidate the anticonvulsant mechanism of triheptanoin and to reveal its clinical potential for the treatment of epilepsy and other disorders of the brain.
Authors:
Karin Borges; Ursula Sonnewald
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2011-08-19
Journal Detail:
Title:  Epilepsy research     Volume:  100     ISSN:  1872-6844     ISO Abbreviation:  Epilepsy Res.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-23     Completed Date:  2012-12-11     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8703089     Medline TA:  Epilepsy Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  239-44     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Affiliation:
Department of Pharmacology, School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia. k.borges@uq.edu.au
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MeSH Terms
Descriptor/Qualifier:
Acyl Coenzyme A / metabolism
Animals
Anticonvulsants / metabolism,  therapeutic use*
Epilepsy / drug therapy*,  metabolism
Fatty Acids / metabolism*
Humans
Triglycerides / metabolism,  therapeutic use*
Grant Support
ID/Acronym/Agency:
R15 NS060105/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Acyl Coenzyme A; 0/Anticonvulsants; 0/Fatty Acids; 0/Triglycerides; 2P6O7CFW5K/triheptanoin; 317-66-8/propionyl-coenzyme A
Comments/Corrections

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