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Carnitine : analytical and physiological aspects

Bourqui, Réjane Morand. Carnitine : analytical and physiological aspects. 2012, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_10023

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Abstract

Carnitine is an endogenous amino acid derivative which plays a key role in energy metabolism. Through acylation of its ß-hydroxy group, carnitine is involved in the interorganellar transport of long-chain fatty acids and in the regulation of the coenzyme A pool. Carnitine is present in most mammalian tissues in its free form or as acylcarnitines of several chain lengths.
The present work consists of three projects investigating analytical and physiological aspects of carnitine and its derivatives and emphasizing the essential function of carnitine in detoxifying processes and energy balance.
The interest of the first project is the carnitine homeostasis in patients treated with the antiepileptic drug valproate. Although generally well tolerated, valproate is associated with carnitine deficiency through an unknown mechanism. We studied the effects of valproate on the carnitine balance in long term patients and in one patient starting a treatment with valproate, as well as in an in vitro model of the renal transport of carnitine by OCTN2.
We show that a patient starting valproate treatment has decreased carnitine plasma concentrations in the initial phase of the therapy. After long term treatment, plasma concentrations of carnitine and acylcarnitines are similar to control patients, with the exception of valproylcarnitine which is only present in treated patients. Urinary excretions of carnitine are substantially lower in valproate patients, suggesting a renal compensatory mechanism. We pointed out that valproylcarnitine although not reabsorbed, barely contributes to the carnitine loss at the beginning of a therapy.
The focus of the second project is the optimization of a LC-MS/MS method for the simultaneous determination of carnitine and acylcarnitines in plasma. For a rapid sample workup, we integrated an online solid phase extraction step to the chromatographic run after protein precipitation. Quantification was achieved with the addition method to account for matrix effects. We report a reliable method for the quantification of carnitine, acetylcarnitine, octanoylcarnitine, and palmitoylcarnitine requiring minimal sample workup, short analysis time and low sample volumes.
In the last project we investigated the effects of carnitine, acetylcarnitine and propionylcarnitine on the carnitine muscle balance and on the performance of mice completing a running exercise until exhaustion. Carnitine and its two acyl-derivatives did not influence the total muscle carnitine content or the physical performance. Accordingly, we did not observe significant differences of muscular respiration or energy parameters such as lactate, glycogen or phosphocreatine between treated and control groups.
Advisors:Krähenbühl, Stephan
Committee Members:Huwyler, Jörg
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmakologie (Krähenbühl)
Item Type:Thesis
Thesis no:10023
Bibsysno:Link to catalogue
Number of Pages:119 S.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:49
Deposited On:23 Aug 2012 10:01

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