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The mutation increases the amount of Ca2+ flow through TPC2 by NAADP evoked signals. This increase in signaling leads to an increase in size of the lysosomes due to the increased rate and amount of fusion. The lysosome, therefore, is not able to break down components the way it should. This inability is associated with the onset of the disease.
The size of lysosomes varies from 0.1 μm to 1.2 μm. [24] With a pH ranging from ~4.5–5.0, the interior of the lysosomes is acidic compared to the slightly basic cytosol (pH 7.2). The lysosomal membrane protects the cytosol, and therefore the rest of the cell , from the degradative enzymes within the lysosome.
Fusion of late endosomes with lysosomes has been shown to result in the formation of a 'hybrid' compartment, with characteristics intermediate of the two source compartments. [8] For example, lysosomes are more dense than late endosomes, and the hybrids have an intermediate density. Lysosomes reform by recondensation to their normal, higher ...
Human LIMP-2 has a theoretical molecular weight of 54.3 kDa and is 478 amino acids in length. [6]Though LIMP-2 was initially discovered in 1985 by Lewis et al. from rat liver lysosomes, [7] LIMP-2 was cloned in 1992 by two groups, one isolated LIMP-2 from human metastatic pancreatic islet tumor cells, and one from rat liver lysosomal membranes.
The enzymes inside of lysosomes are acid hydrolases which require an acidic environment for optimal performance. Lysosomes provide such an environment by maintaining a pH of 5.0 inside of the organelle. [37] If a lysosome were to rupture, the enzymes released would not be very active because of the cytosol's neutral pH.
[4] [5] Therefore, microsomes are a valuable tool for investigating the metabolism of compounds (enzyme inhibition, clearance and metabolite identification) and for examining drug-drug interactions by in vitro-research. Researchers often select microsome lots based on the enzyme activity level of specific CYPs.
The autophagic process is divided into five distinct stages: Initiation, phagophore nucleation, autophagosomal formation (elongation), autophagosome-lysosome fusion (autophagolysosome) and cargo degradation. [1] An autophagosome is a spherical structure with double layer membranes. [2]
The CI-MPR and CD-MPR bind mannose 6-phosphate in a similar fashion. Both form a set of hydrogen bonds between key residues and characteristic hydroxyl groups on the mannose residue. Hydrogen bonds to hydroxyl groups at positions 2, 3 and 4 make the site specific for mannose alone. Both MPRs share 4 residues that are essential for ligand binding.
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