Lysosomes, protein catabolism

Does defective lysosomal catabolism in I-cell disease somehow feed back to affect the expression of lysosomal proteins and their receptors Compared with control fibroblasts, twofold increases in man-6-P/IGF-II receptors have been observed for fibroblasts from patients with I-cell disease. This increase in receptor concentration stems from an increased rate of synthesis, not from differences of receptor stability. Interestingly, when they are exposed to insulinlike growth factors I and II or tumor-promoting phorbol esters, I-cell fibroblasts respond differently from control fibroblasts. These observations indicate multiple regulatory sites in the man-6-P/IGF-II receptor pathway. 

Furst W, Sandhoff K. Activator proteins and topology of lysosomal sphingolipid catabolism. Biochim. Biophys. Acta 1992 1126 1-16. 

Dawson G, Cho S. Batten s disease clues to neuronal protein catabolism in lysosomes. J Neurosci Res 2000 60(2) 133... 

In eukaryotes, anabolic and catabolic pathways that interconvert common products may take place in specific subcellular compartments. For example, many of the enzymes that degrade proteins and polysaccharides reside inside organelles called lysosomes. Similarly, fatty acid biosynthesis occurs in the cytosol, whereas fatty... 

Moore, M. N. and Viarengo, A. (1987). Lysosomal membrane fragility and catabolism of cytosolic proteins evidence for a direct relationship, Experientia, 15, 320-323. 

Fig. 6.2. Model for how FcRn rescues IgG from catabolism by recycling and transcytosis. IgG and many other soluble proteins are present in extracellular fluids. Vascular endothelial cells are active in fluid phase endocytosis of blood proteins. Material taken up by these cells enters the endosomes where FcRn is found as an integral membrane protein. The IgG then binds FcRn in this acidic environment. This binding results in transport of the IgG to the apical plasma membrane for recycling into the circulation, or to the basolateral membrane for transcytosis into the extracellular space. Exposure to a neutral pFI in both locations then results in the release of IgG. The remaining soluble proteins are channeled to the lysosomal degradation pathway.

The majority of body iron is not chelatable (iron from cytochromes and hemoglobin). There are two major pools of chelatable iron by DFO (19). The first is that delivered from the breakdown of red cells by macrophages. DFO competes with transferrin for iron released from macrophages. DFO will also compete with other plasma proteins for this iron, when transferrin becomes saturated in iron overload. The quantity of chelatable iron from this turnover is 20mg/day in healthy individuals and iron chelated from this pool is excreted in the urine (19). The second major pool of iron available to DFO is derived from the breakdown of ferritin and hemosiderin. The ferritin is catabolized every 72 hours in hepatocytes, predominantly within lysosomes (I). DFO can chelate iron that remains within lysosomes shortly after ferritin catabolism or once this iron reaches a dynamic, transiently chelatable, cytosolic low-molecular-weight iron pool (20). Cellular iron status, the rate of uptake of exogenous iron, and the rate of ferritin catabolism are influent on the level of a labile iron pool (21). Excess ferritin and... 

The cell surface receptors also remove the carboxy terminal arginine residue from RBP, thus inactivating it by reducing its affinity for both transthyretin and retinol. As a result, apo-RBP is filtered at the glomerulus. Some may be lost in the urine, but most is resorbed in the proximal renal tubules and is then catabolized by lysosomal hydrolases. This seems to be the main route for catabolism of RBP the apo-protein is not recycled (Peterson et al., 1974). 

Other enzymatic means of removing protein carbonyls involve carbonyl reductase and aldehyde dehydrogenase. The majority of the oxidized proteins are catabolized by proteasomal and lysosomal pathways, but some materials appear to be poorly degraded and accumulate within the cell (Dean et al., 1997 Grune et al.,... 

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