This thesis includes a series of investigations which were directed towards a detailing of structure-function relationships of mammalian catalases to further the understanding of the relationships between this enzyme and its physiological and cytological millieu. In so doing information of contemporary interest in the fields of phylogeny , enzyme multiplicity, sub-cellular localization and microlocalization, turnover, and physiological function is presented.
Initially, comparative studies established that the existence of native catalase multiplicity was species specific and showed that multiple forms of activity characteristic of tissues or sub-cellular fractions could be resolved in the case of the rat and the mouse. Also, catalase activity in the rat and the mouse proved more labile than in species which displayed no such native heterogeneity.
In order to clarify the nature of this heterogeneity, the enzyme from mouse liver was purified and the properties of the individual multiple forms examined , whereupon it was established that the native multiple forms could be interconverted under conditions favouring addition or removal of sialic acid. From these results the proposal arose that the multiple forms characteristic of the cytosol were derived from those characteristic of the peroxisomes in the course of a biodegradative process, which removed sialic acid and independently partially destroyed the activity of the enzyme. Subsequently, pulse labelling techniques were used to establish that the pools of catalase activity in the mouse as well as the individual heteromorphs were related to each other in a product-precursor fashion. Further data on the mechanisms of catalase degradation was obtained by the measurement of turnover parameters in guinea pig, mouse and acatalasaemic mouse and the correlation of these widely differing values with the susceptibility of the catalases to in vitro proteolysis.
In an endeavour to shed light on the relationships between catalase and peroxisomal biosynthesis, the effect of the inhibitor AT and the inducer CTIB on the pools of activity and the multiple forms of catalase in mouse liver was examined ;and this biochemical evidence used in conjunction with morphological examination of peroxisomes histochemically stained for catalase activity in order to propose a model for peroxisomal biogenesis and catalase synthesis, intracellular sequestration and degradation.
Finally, in an attempt to establish the physiological significance of catalase in relation to lipid metabolism the influence of variations in liver catalase levels on the lipid composition of plasma,liver and carcass has been examined.