Biotin deficiency in the rat as a model for reduced pyruvate carboxylase activity

The investigations described in this thesis are a contribution to the study of Leigh's disease (Subacute Necrotizing Encephalomyelopathy, SNE). SNE resembles in neuropathology Wernicke's encephalopathy, which is caused by thiamine deficiency. The scope and the purpose of the present study is given in the introduction (chapter 1). From a review of the selected literature, given in chapter 2, it will be clear that the pathogenesis of Leigh's disease is far from understood. The expirimental procedures used in the investigations described , are outlined in chapter 3. The investigations focus on the following aspects: -1- a synthesis of thiamine triphosphate in vitro (chapter 4), -2- biotin deficiency in the newborn rat as an animal model for reduced pyruvate carboxylase activity in man (chapter 5 and 6), -3- the effect of thiamine on carbohydrate metabollism of normal rats and rats which slow lactic acidosis as a result of biotin deficiency (chapter 7). ... Zie: Summar