Biochemistry 4463G Lecture Notes - Lysosomal Storage Disease, Glucocerebrosidase, Glucocerebroside
25 Apr 2013
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Document Summary
A lysosomal storage disease and a model for future therapies of some genetic disorders. Lysosomal storage disease glucocerebrosidase substrate accumulates. Lysosome: small, sub-cellular organelle in most cells, contains 60-80 enzymes that break down proteins. Lysosomes are very acidic (ph 4 5), degradive enzymes that do not float around the body. The substrate for this enzyme is only found in certain tissues. Failure to thrive (ex. inability to swallow) Individuals tend to have an enlarged spleen and liver. Two phenomena tend to happen to the cell: apoptosis & inflammatory response (from material storage) There is an accumulation of undergraded substrate = glucocerebroside. The penultimate step in the catabolism of more complex glycolipids that are present in many tissues. Clinical manifestations reflect cellular sites of substrate storage. Macrophages phagocytes formed elements of blood which have accumulated glucosylceramide. Most prominent in spleen, bone marrow, kupffer cells and alveolar macrophages. We measure glucocerebrosidase level in leukocytes (that lack the enzyme in the diseased state)
