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• W2885155477 abstract "During the fed state energy requirements are met by glycolysis of carbohydrates. When the stores of carbohydrates are diminished, for example during prolonged fasting, metabolism switches to that of fatty acids. Fatty acids are broken down by fi-oxidation within the mitochondrial matrix. Prolonged fasting results in the production of ketone bodies. These can also be used as an energy source by the brain. In defects of fatty acid metabolism where individual steps are inhibited or blocked, such as medium chain acyl-CoA dehydrogenase deficiency, an abnormal accumulation of the metabolites that lead up to the block, or their breakdown products, is often seen. Non-compensatory levels of metabolites following the site of the defect also occur. In the fed state, when flux through the defective fatty acid pathway is minimal, metabolic profiles can appear completely normal. It is therefore often necessary to induce metabolic stress before a full laboratory investigation can proceed. Interpretation of individual metabolite quantitations can often be difficult and a variation of 'normal values' according to metabolic state can lead to misinterpretation. Comparison between the concentrations of related metabolites along the fatty acid metabolic pathway may diminish the need for exact knowledge of the metabolic state and by correlation plotting could clearly identify abnormal relationships. This thesis describes an investigation into the efficacy of paired metabolite correlation plots in preliminary detection of defects in fatty acid metabolism. In certain inborn errors of fatty acid metabolism where the fi-oxidation cycle is affected, abnormal urine metabolite patterns have been used as diagnostic markers. Similar patterns have been reported in the urine of healthy newborns and termed generalised neonatal dicarboxylic aciduria177. This report documents an investigation of the connections between generalised neonatal dicarboxylic aciduria and a number of overlying factors (vis type of feed, gender, sibling history of sudden infant death syndrome and urine carnitine levels). Also discussed is the development of two laboratory assays. A radio-enzymatic method was developed and used to determine the levels of total, free and acyl carnitine in urine or blood. Suberyl, hexanoyl, and phenylpropionyl glycine in urine can be quantitated by use of stable isotope internal standards and gas chromatography / electron impact mode mass spectrometry. Synthesis and calibration of such internal standards is described. Finally, methods used to culture and store skin fibroblasts from biopsy samples are included as an appendix. These fibroblasts can then be used in various diagnostic tests such as carbon dioxide release and electron transfer flavoprotein enzyme analysis. The costs encountered during tissue culture could be avoided by medium term storage of the biopsy material prior to culture to await sufficient clinical evidence to merit such analyses. Preliminary results of extended cryogenic storage and viability of recovered specimens are also included." @default.
• W2885155477 created "2018-08-22" @default.
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• W2885155477 date "1992-01-01" @default.
• W2885155477 modified "2023-09-27" @default.
• W2885155477 title "Indices of fatty acid metabolism." @default.
• W2885155477 hasPublicationYear "1992" @default.
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