42 research outputs found

    Reflections on amyloidosis in Papua New Guinea

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    The amyloidoses comprise a heterogeneous group of diseases in which 1 out of more than 25 human proteins aggregates into characteristic beta-sheet fibrils with some unique properties. Aggregation is nucleation dependent. Among the known amyloid-forming constituents is the prion protein, well known for its ability to transmit misfolding and disease from one individual to another. There is increasing evidence that other amyloid forms also may be transmissible but only if certain prerequisites are fulfilled. One of these forms is systemic AA-amyloidosis in which an acute-phase reactant, serum AA, is over-expressed and, possibly after cleavage, aggregates into amyloid fibrils, causing disease. In a mouse model, this disorder can easily be transmitted from one animal to another both by intravenous and oral routes. Also, synthetic amyloid-like fibrils made from defined small peptides have this property, indicating a prion-like transmission mechanism. Even some fibrils occurring in the environment can transmit AA-amyloidosis in the murine model. AA-amyloidosis is particularly common in certain areas of Papua New Guinea, probably due to the endemicity of malaria and perhaps genetic predisposition. Now, when kuru is disappearing, more interest should be focused on the potentially lethal systemic AA-amyloidosis

    Equations of Substrate-inhibition Kinetics Applied to Pig Kidney Diamine Oxidase (DAO, E.C. 1.4.3.6)

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    Pig kidney diamine oxidase (DAO) and other semicarbazide-sensitive amine oxidases (SSAO) show clear substrate-inhibition kinetics and a reaction-scheme mechanism based on two substrate binding sites. We evaluated several reaction scheme mechanisms with a non-linear regression program (NCSS), estimating R2, the constants of the equations and their standard errors and we determined the deviation of experimental data from theoretical equations. The best fit was obtained with a "dead end" mechanism with two binding sites. Based on this scheme, other schemes for a two-substrate reaction and for mechanisms of inhibition were constructed. These reaction schemes, even at low substrate concentration, fitted experimental data better than Michaelis-Menten kinetics, and provided information on the mechanisms of action of inhibitors. The presence of two substrate-binding sites on pig kidney DAO was confirmed by all experimental data
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