Cellular death Lysosome

Previous studies have shown that muscle lysosomal hydrolases are released early in the postmortem period due to a decrease in intracellular ATP concentrations. The decreased intracellular ATP level causes the rupture of the lysosomal membrane (14), releasing hydrolytic enzymes (proteases, lipases, and glycosidases) that further potentiate the weakening of membrane integrity and cellular function. Furthermore, as the acidosis increases (due to the anaerobic conditions associated with cellular death) the intramuscular pH to levels reach that which are optimal for the activity of several lysosomal thiol proteinases. 

Oxidized LDL alter cellular functions role in cell death Oxidized LDL seem to be poorly degraded by lysosomal enzymes and accumulate in lysosomes altering in turn their functionality (Dean et al., 1997). It has been proposed that inhibition of oxidized LDL degradation and subsequent lipid accumulation may induce a destabilization of the acidic compartment, and lysosomal rupture with a relocation of lysosomal enzymes in the cytosol (li W et al, 1998). This process, also called endopepsis , occurs early and could precede mitochondrial dysfunction and cell death (Lossel et al., 1994). Moreover, oxidized LDL trigger a dysfunction of the intracellular proteolytic ubiquitin/proteasome pathway (early activation followed by inhibition)... 

The general scheme for the degradation of nucleic acids has much in common with that of proteins. Nucleotides are produced by hydrolysis of both dietary and endogenous nucleic acids. The endogenous (cellular) polynucleotides are broken down in lysosomes. DNA is not normally turned over rapidly, except after cell death and during DNA repair. RNA is turned over in much the same way as protein. The enzymes involved are the nucleases deoxyribonucleases and ribonucleases hydrolyze DNA and RNA, respectively, to oligonucleotides which can be further hydrolyzed (Fig. 15-18), so eventually purines and pyrimidines are formed. 

Several lysosomal storage diseases result from defective expression of specific glycosidases. The intracellular accumulation of unprocessed carbohydrate substrates leads to aberrant cellular structure and cell death. Thus, deficient or defective hexosaminidase results in either Tay-Sachs or Sandhoff disease [157]. Fucosidosis, another neurovisceral storage disease, is caused by defective a-L-fucosidase expression. 

What would happen if the hydrolytic enz)Tmes of the lysosome were accidentally released into the cytoplasm of the cell Certainly, the result would be the destruction of cellular macromolecules and death of the cell. Because of this danger, the cell invests a great deal of energy in maintaining the integrity of the lysosomal membranes. An additional protective mechanism relies on the fact that lysosomal enzymes fimction optimally at an acid pH (pH 4.8). Should some of these enzymes leak out of the lysosome or should a lysosome accidentally rupture, the cytoplasmic pH of 7.0-7.3 renders them inactive. 

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