At the present time a large number of inherited human disorders are known which are characterized by abnormally large intra-lysosomal accumulations of undegraded or partially degraded macromolecules; such lysosomal storage disorders typically result from gene mutations leading to the absence or defective production of specific lysosomal hydrolases normally required in the sequential chain of hydrolytic reactions. Much less common is a form of storage disorder in which there is an abnormally large intra-lysosomal accumulation of an end product of macromolecular degradation. The most notable example of this type of disorder occurs in human cystinosis, in which there is an abnormally large intra-lysosomal accumulation of the amino acid cystine, an end product of protein catabolism; previous work in our laboratories has indicated strongly that this disorder is the result of a defective carrier mechanism normally required for the trans-membrane movement of this amino acid. More recently, we have been investigating a possibly analogous disorder characterized by massive intracellular storage of free sialic acid, an important constituent of the polysaccharide moiety of glycoproteins and of glycolipids. Preliminary results, carried out with cultured cells from a patient with severe sialic acid storage disease, indicate that the free sialic acid found therein is localized primarily within the lysosomal compartment; furthermore, the rate of escape of the monosaccharide from the isolated lysosome-rich fraction of such cells occurs more slowly than that noted with the corresponding fraction from normal cells which have been preloaded with free sialic acid. This form of sialic acid storage disease may constitute another example of a disorder caused by the impaired movement of a metabolite across the lysosomal membrane.

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Arthritis, Diabetes, Digestive & Kid Dis
United States
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