Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292853
Title: Development of gas chromatography/mass spectrometry analysis of urinary acylcarnitines : application to metabolism studies
Author: Lowes, Stephen
ISNI:       0000 0001 3613 376X
Awarding Body: Open University
Current Institution: Open University
Date of Award: 1991
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
The metabolism of fatty acids in humans is recognized as an important source of energy. It is especially vital to newborn infants when metabolic pathways are often stressed as the early stages of life demand fundamental changes and developments of body processes. Defective fatty acid oxidation pathways can rapidly lead to a life-threatening situation. It has been suggested that such disorders may be responsible for a proportion of "cot death" or sudden infant death syndrome (SID S) cases. Recently, it has been found that the levels of acylcarnidnes in body fluids and tissue are potential indicators of fatty acid metabolism status. This is due to carnitine esters being produced and excreted in an attempt to alleviate the toxic accumulation of incompletely metabolized acyl units in the mitochondrion. However, clinical studies have been limited by a lack of convenient, unambiguous, sensitive and affordable analytical techniquesf or the measuremenot f physiological acylcarnitmnes. The nature of carnitine and its acyl esters presents analysis problems. They are involatile, zwitterionic compounds which makes them unsuitable for direct gas chromatography (GC) and combined gas chromatography/mass spectrometry (GCIMS). The latter of these is the favoured technique for normal urinary organic acid assays and is ideal in terms of selectivity and sensitivity. The work reported here details the development of a simple unambiguous and novel derivatization procedure in which acylcarnitines are cyclized to give volatile lactones, amenable to GC and GC/MS. The technique was subsequently applied to acylcarnitines extracted from urine. As such, the method has been used to identify acylcarnitine metabolites in the urine of children with diseases of fatty acid oxidation and amino acid catabolism. Investigations of the metabolism of exogenous 3-phenylpropionic and valproic acids was also conducted. The preliminary results from the application of capillary zone electrophoresis methods to acylcarnitine analysis are also reported.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.292853  DOI: Not available
Keywords: Biochemistry
Share: