Document Detail


Carnitine and Acylcarnitines: Pharmacokinetic, Pharmacological and Clinical Aspects.
MedLine Citation:
PMID:  22804748     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
L-Carnitine (levocarnitine) is a naturally occurring compound found in all mammalian species. The most important biological function of L-carnitine is in the transport of fatty acids into the mitochondria for subsequent β-oxidation, a process which results in the esterification of L-carnitine to form acylcarnitine derivatives. As such, the endogenous carnitine pool is comprised of L-carnitine and various short-, medium- and long-chain acylcarnitines. The physiological importance of L-carnitine and its obligatory role in the mitochondrial metabolism of fatty acids has been clearly established; however, more recently, additional functions of the carnitine system have been described, including the removal of excess acyl groups from the body and the modulation of intracellular coenzyme A (CoA) homeostasis. In light of this, acylcarnitines cannot simply be considered by-products of the enzymatic carnitine transfer system, but provide indirect evidence of altered mitochondrial metabolism. Consequently, examination of the contribution of L-carnitine and acylcarnitines to the endogenous carnitine pool (i.e. carnitine pool composition) is critical in order to adequately characterize metabolic status. The concentrations of L-carnitine and its esters are maintained within relatively narrow limits for normal biological functioning in their pivotal roles in fatty acid oxidation and maintenance of free CoA availability. The homeostasis of carnitine is multifaceted with concentrations achieved and maintained by a combination of oral absorption, de novo biosynthesis, carrier-mediated distribution into tissues and extensive, but saturable, renal tubular reabsorption. Various disorders of carnitine insufficiency have been described but ultimately all result in impaired entry of fatty acids into the mitochondria and consequently disturbed lipid oxidation. Given the sensitivity of acylcarnitine concentrations and the relative carnitine pool composition in reflecting the intramitochondrial acyl-CoA to free CoA ratio (and, hence, any disturbances in mitochondrial metabolism), the relative contribution of L-carnitine and acylcarnitines within the total carnitine pool is therefore considered critical in the identification of mitochondria dysfunction. Although there is considerable research in the literature focused on disorders of carnitine insufficiency, relatively few have examined relative carnitine pool composition in these conditions; consequently, the complexity of these disorders may not be fully understood. Similarly, although important studies have been conducted establishing the pharmacokinetics of exogenous carnitine and short-chain carnitine esters in healthy volunteers, few studies have examined carnitine pharmacokinetics in patient groups. Furthermore, the impact of L-carnitine administration on the kinetics of acylcarnitines has not been established. Given the importance of L-carnitine as well as acylcarnitines in maintaining normal mitochondrial function, this review seeks to examine previous research associated with the homeostasis and pharmacokinetics of L-carnitine and its esters, and highlight potential areas of future research.
Authors:
Stephanie E Reuter; Allan M Evans
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-17
Journal Detail:
Title:  Clinical pharmacokinetics     Volume:  -     ISSN:  0312-5963     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7606849     Medline TA:  Clin Pharmacokinet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
School of Pharmacy Medical Sciences, University of South Australia, Adelaide, SA, Australia.
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