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    Interpretasie van β-oksidasie metaboliet profiele : 'n metabolomika gebaseerde benadering

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    Date
    2005
    Author
    Taute, Cornelius Johannes Frans
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    Abstract
    Metabolomics is an emerging field and requires a global approach to metabolism. It describes how varying factors (diet, exercise, disease, etc.) influences metabolism. A metabolomic approach can not only make it easier to detect changes in metabolic conversion but also shed new light on mechanisms in metabolism. Biomarkers for a given metabolic disease can easily be detected in the urine by conventional metabolic screening tests such as Gas Chromatography-Mass Spectrometry analysis of organic acids and Liquid Chromatography-Tandem Mass Spectrometry analysis of acylcarnitines for homozygote patients. With this metabolomics based approach it might become easier to also detect heterozygote patients by grouping of the same biomarkers. In order to see if this is possible a metabolomics based approach was used in this study to see if heterozygotes with defects in mitochondria1 P-oxidation can be diagnosed. Two approaches were used. The effect of L-carnitine supplementation on Poxidation in normal persons were studied to generate reference values. Heterozygote members of two families with different inborn errors in their fatty acid oxidation (Medium Chain Acyl-CoA Dehydrogenase Defect and Multiple Acyl-CoA Dehydrogenase Defect) were diagnosed by conventional urine tests. A linear summation technique was designed and applied to the data obtained from the two families. The heterozygote members of both families had significantly elevated concentration values above reference values, but not so high as the homozygote members. Thus it can be concluded that heterozygote patients can be detected with urine tests with the use of the newly designed linear summation technique. Basic- and advanced acylcarnitine ratios were calculated to enhance the differentiation between selected medications and diseases affecting β-oxidation with varying degrees of success. The acylcarnitine ratios that were calculated are only useful when it is already known that the disease is a defect of P-oxidation. It nonetheless gave an indication that this approach can be useful to diagnose heterozygote patients.
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    http://hdl.handle.net/10394/1332
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    • Natural and Agricultural Sciences [2757]

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