Lysosomes Physiological role

C5a is inactivated by the myeloperoxidase-H202 system, which oxidises a methionine residue (Met 70) on the molecule group A streptococcal endo-proteinases also abolish chemotactic activity of C5a and related compounds. Neutrophil lysosomal enzymes (e.g. elastase and cathepsin G) also destroy C5a chemotactic activity, but as these proteases are inhibited by the serum antiproteinases, a -antiproteinase and a2-macroglobulin, the physiological role of neutrophilic proteases in the inactivation of C5a is questionable. Two chemotactic factor inactivators have been found in human serum an a-globulin that specifically and irreversibly inactivates C5-derived chemotactic factors, and a / -globulin that inactivates bacterial chemotactic factors. These activities are heat labile (destroyed by treatment at 56 °C for 30 min) and are distinct from those attributable to anaphylatoxin inactivator. An apparently specific inhibitor of C5-derived chemotactic activity has also been described in human synovial fluid and peritoneal fluid. This factor (molecular mass of 40 kDa) is heat stable and acts directly on C5a. 

Kohn, M. C., and Melnick, R. L. (1999). A physiological model for ligand-induced accumulation of alpha 2u globulin in male rat kidney Roles of protein synthesis and lysosomal degradation in the renal dosimetry of 2,4,4-trimethyl-2-pentanol. Toxicology 136, 89-105. 

There are two direct consequences of insulin binding to the receptor. First the tyrosine kinase activity on the / -subunit is activated. This causes autophosphorylation and also phosphorylation of intracellular proteins. Although a number of proteins have been phosphorylated in vitro, it is not yet clear what is the normal physiological substrate or substrates. In mammals, several cellular protein substrates have been proposed, but the precise role of any of the proteins is unclear. A 70 kDa protein has been proposed as a substrate in cultured foetal chick neurons, and a 72 kDa phosphoprotein in domestic fowl hepatoma, but the functions of these polypeptides are unclear (Simon Taouis, 1993). Second, binding causes internalisation of the receptor, after which the insulin is removed and degraded in the lysosomes and the receptor recycled back to the plasmalemma. In domestic fowl hepatocytes, the half-life of the receptor is about 10 h (Simon, 1989). 

In addition, the in situ localization of RPH activity within the liver cell still remains to be defined. It was suggested (Prystowsky et al., 1981) that the unusual subcellular distribution observed might have resulted in part from the hydrophobic physical properties of the enzyme, which led it to become absorbed to particulate material (i.e., membranous components) that sediments in the nuclear (and mitochondrial-lysosomal) fraction. Within the cell, these hydro-phobic properties may well direct the enzyme to be associated with retinyl ester-containing lipid droplets or lipid-protein aggregates (discussed further below). Thus, the hydrophobic properties of the enzyme may be physiologically involved in enabling it to perform its role of catalyzing lipid ester hydrolysis. 

More problematic and more controversial is the biological role of uteroferrin. Present in allantoic fluid in concentrations often exceeding 2 mg/ml (5 X 10" M), it is hard to imagine an enzymatic function for this protein in the physiological compartment in which it abounds. Conceivably, it is simply leaked into the allantoic fluid by hyperproducing lining cells of the allantoic membrane, for which uteroferrin functions as a lysosomal acid phosphatase ). An alternative possibility is that uteroferrin functions not as an enzyme, since it is almost inactive at the pH of the fluid in which it is found, but as a carrier of iron from sow to fetal pig ). 

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