Enzymes in lysosomes

Hydrolytic enzymes In lysosome attack LDL products pass Into cytosol... 

The polar lipids of membranes undergo constant metabolic turnover, the rate of their synthesis normally counterbalanced by the rate of breakdown. The breakdown of lipids is promoted by hydrolytic enzymes in lysosomes, each enzyme capable of hydrolyzing a specific bond. When sphingolipid degradation is impaired by a defect in one of these enzymes (Fig. 1), partial breakdown products accumulate in the tissues, causing serious disease. 

The importance of buffers in all areas of science is immense. At the outset of this chapter, we saw that digestive enzymes in lysosomes operate best in acid, which allows a cell to protect itself from its own enzymes. If enzymes leak into the buffered, neutral cytoplasm, they have low reactivity and do less damage to the cell than they would at their optimum pH. Figure 9-3 shows the pH dependence of an enzyme-catalyzed reaction that is fastest near... 

Lysosomes are subcellular organelles in which a wide range of catabolic enzymes are stored in a closed, protective membrane system. They are major sites of intracellular digestion of complex macromolecules derived from both intracellular (autophagic) and extracellular (het-erophagic) sources. Lysosomal enzymes show optimal activity at acidic pH. The pattern of enzymes in lysosomes may depend upon the tissue of origin, as well as upon the physiological or developmental state of the cells. 

Sly, W.S., Natowicz, M., Gonzalez-Noriega, A., Grubb, J.H. and Fischer, H.D. (1981). The Role of the Mannose-6-Phosphate Recognition Marker and its Receptor in the Uptake and Intracellular Transport of Lysosomal Enzymes in Lysosomes and Lysosomal Storage Diseases (Callahan, J.W. and Lowden, J.A., eds), Raven Press, New York, pp. 131-146. 

Barrett, A. J., Heath, M. F. Lysosomal enzymes, in Lysosomes, a laboratory handbook (ed.) Dingle, J. T., p. 19, Amsterdam, Elsevier/North-Holland Biomedical Press 1977... 

As indicated above, Man 6-P serves as a chemical marker to target certain lysosomal enzymes to that organelle. Analysis of cultured fibroblasts derived from patients with I-cell (inclusion cell) disease played a large part in revealing the above role of Man 6-P. I-cell disease is an uncommon condition characterized by severe progressive psychomotor retardation and a variety of physical signs, with death often occurring in the first decade. Cultured cells from patients with I-cell disease were found to lack almost all of the normal lysosomal enzymes the lysosomes thus accumulate many different... 

Srivastava L, Tandon SK. 1984. Effects of zinc on lead-induced changes in brain lysosomal enzymes in the chick embryo. Toxicol Lett 20 111-114. 

Hydrolysis of triacylglycerides in tissues is effected by a tissue enzyme, tri-acylglyceride lipase, which hydrolyzes triacylglycerides to glycerol and free fatty acids. There are a variety of tissue lipases that differ primarily in their optimum pH and their location in the cell. The acidic lipase is contained in lysosomes the basic lipase, in microsomes and the neutral lipase, in cytoplasm. A specific feature of the tissue lipase is its sensitivity to hormones which, by activating adenylate cyclase, elicit the transition of the inactive tissue lipase to its active... 

Munier-Lehmann, H., Mauxion, F. and Hoflack, B. Function of the two mannose 6-phosphate receptors in lysosomal enzyme transport. Biochem. Soc. Trans. 24 133-136,1996. 

Defect in lysosomal enzyme protection Defects in soluble non-enzymatic lysosomal proteins... 

Ludwig, T., Le Borgne, R., and Hoflack, B. (1995). Roles for mannose-6-phosphate receptors in lysosomal enzyme sorting, IGF-II binding and clathrin-coat assembly. 

PS that localize in lysosomes tend to produce apoptosis more slowly after illumination than mitochondrial PS, due to the release of lysosomal enzymes that subsequently activate cytoplasmic caspases (Kessel et al., 2000). 

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)... 

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