Urinary excretion of minor matabolites produced by critate synthase condensation in patients with propionic acidaemia.

Abstract

The title of this thesis; "Urinary Excretion of minor Metabolites produced by Citrate Synthase condensation in Patients with Propionic Acidaemia" impound a fine description of the metabolic deficiency and the pathway important for this study. Propionic acidaemia, an inherited metabolic disorder of propionic acid due to a propionyl-CoA carboxylase deficiency, is characterized mainly by severe keto acidosis. The cause for the massive metabolic keto acidosis is still not clear, but several studies have indicated that this condition could be caused by inhibition of the TCA-cycle by one or more of the abnormal metabolites produced in this cycle. Until now the isomers of methylcitric acid (a two chiral center product catalyzed by citrate synthase condensation of propionyl-CoA and oxaloacetic acid and present in high concentrations in patients with propionic acidaemia) have been studied and it was found that some of the isomers may have the ability to inhibit aconitase (Cheema-Dhadli et al. , 1975). However Beach and coworkers (1977) used all four the isomers of methylcitric acid in an aconitase inhibition study and concluded that methylcitric acid is neither a substrate nor does it inhibit aconitase. These discrepancies led to many uncertainties about the influence of citrate synthase products on the TCA-cycle. In this chapter an overview of propionic acidaernia and findings around the citrate synthase reaction will be discussed. All the metabolic pathways, enzymes and inconsistencies regarding these aspects will be reviewed in detail to understand the aim of this study.