Liver lysosomes

In contrast with the variety of methods of extraction of LAS from other solid samples (such as sediment, suspended solid, sludge) and water samples (see corresponding section), there are relatively few reports of attempts to extract LAS from biological samples [22-28]. Direct HPLC measurement of accumulation of LAS in rat liver lysosomes has been reported [29]. 

The intracellular localization of carboxylesterases is predominantly microsomal, the esterases being localized in the endoplasmic reticulum [73] [79] [93], They are either free in the lumen or loosely bound to the inner aspect of the membrane. The carboxylesterases in liver mitochondria are essentially identical to those of the microsomal fraction. In contrast, carboxylesterases of liver lysosomes are different, their isoelectric point being in the acidic range. Carboxylesterase activity is also found in the cytosolic fraction of liver and kidney. It has been suggested that cytosolic carboxylesterases are mere contaminants of the microsomal enzymes, but there is evidence that soluble esterases do not necessarily originate from the endoplasmic reticulum [94], In guinea pig liver, a specific cytosolic esterase has been identified that is capable of hydrolyzing acetylsalicylate and that differs from the microsomal enzyme. Also, microsomal and cytosolic enzymes have different electrophoretic properties [77]. Cytosolic and microsomal esterases in rat small intestinal mucosa are clearly different enzymes, since they hydrolyze rac-oxazepam acetate with opposite enantioselectivity [95], Consequently, studies of hydrolysis in hepatocytes reflect more closely the in vivo hepatic hydrolysis than subcellular fractions, since cytosolic and microsomal esterases can act in parallel. 

Fig. 6.33. The structure of human calcitonin (compare with salmon calcitonin in Fig. 6.22). The descending arrows indicate sites of cleavage in rat liver lysosomal fraction (full arrows) and rat liver and kidney cytosolic fractions (broken arrows). The ascending arrows indicate sites of cleavage by cathepsin B1 (full arrows) and cathepsin D (broken arrows) [149].

V. Patel and A. L. Tappel, Identity of P-glucosidase and P-xylosidase activities in rat liver lysosomes, Biochim. Biophys. Acta Enzymol., 191 (1969) 653-662. 

The Morquio syndrome (type IV mucopolysaccharidosis) is associated with the excretion of large amounts of keratan sulfate in the urine.389 The patients appear to have a normal pattern of enzymic activities in the liver lysosomes.399 Types V (Scheie syndrome) and... 

Nucleotidases have been studied in liver from various species and activity has been identified in lysosomes, cytoplasmic supernatants and plasma membrane preparations. Arsenis and Touster (31) have purified a 5 -nucleotidase from rat liver lysosomes to apparent homogeneity. The enzyme is unusual in that it hydrolyzes 2 -, 3 -, and 5 -mononucleotides equally well with preference for 5 -dAMP. It also hydrolyzes FMN, p-nitrophenyl phosphate, and /J-glycerol phosphate, but not inorganic pyrophosphate or bis(p-nitrophenyl) phosphate. Unlike the 5 -nucleotidases described thus far, divalent cations such as Co2+, Mn2+, and Mg2+ have no activating effect, but EDTA is inhibitory. In spite of the broad substrate specificity kinetic experiments indicate that a single enzyme is involved. Because of its broad substrate specificity it has been suggested (SI) that it may play a key role in lysosomal catabolism of nucleic acids. 

The most notable similarities relate to activation and inactivation by metal ions and other materials. In most instances (Table I) each is activated by one or more of the cations Co2+, Mn2+, Ni2+, Mg2+, or Ca2+ of which the former three are usually most effective. Here again, however, there are differences. Thus, the B. atrox enzyme is not activated by ions, but they serve to reverse EDTA inhibition (23). The rat liver lysosomal enzyme is also not activated by divalent metals (SI) the sheep brain enzyme does not seem to require divalent cation and in fact it is inhibited by Co2+ (57). 

Hinz B, Hirschelmann R. Dexamethasone megadoses stabilize rat liver lysosomal membranes by non-genom-ic and genomic effects. Pharm Res. 2000 17 1489-1493. 

Matsuzawa, Y. and Hostetler, K. Y. (1980) Properties of phospholipase C isolated from rat liver lysosomes, J. Biol. Chem. 255, 646-652. 

Many tissues from patients with I-cell disease exhibit normal levels of intracellular lysosomal enzymatic activities (e.g., brain, liver, kidney, and spleen). In the liver, lysosomal enzyme levels are normal except for diminished P-galactosidase and elevated P-hexosaminidase, P-xylosidase.and a-galactosidase. This fairly spe-... 

Tsuji, A., Akamatsu, T., Nagamune, H., Matsuda, Y. (1994). Identification of targeting proteinase for rat alpha 1-macro-globulin in vivo. Mast-cell tryptase is a major component of the alpha 1-macroglobulin-proteinase complex endoc dosed into rat liver lysosomes. Biochem. J. 298 79-85. 

Sawant, P. L., Shibko, S., Kumta, U. S., and Tappel, A. L., Isolation of rat-liver lysosomes and their general properties. Biochim. Biophys. Acta 85, 82-92 (1964). 

Some of these enzymes were found in the blister fluid produced arti-fically with cantharidin and the activities were most likely released from the lysosomes of epidermal cells (S14). There are, however, considerable differences between the reactions of liver lysosomes and epidermal lysosomes. Dicken and Decker (Dl) found that while Triton X-100 caused release of latent acid phosphatase activity from epidermal lysosomes acid pH, hypotonic solutions, and freezing and thawing which are effective disrupters of liver lysosomes did not disrupt epidermal lysosomes. Smith et al. (S16) found that capsaicin and cantharidin also would not lyse epidermal lysosomes and they substantiated Dicken s finding that Triton X-100 did cause lysis. 

B. Fiszer-Szafarz. Hyaluronidase polymorphism detected by polyacrylamide gel electrophoresis. Application to hyaluronidases from bacteria, slime molds, bee and snake venoms, bovine testes, rat liver lysosomes and human serum. Anal. Biochem. 143 16 (1984). 

Saint-Pol, A., Codogno, P., and Moore, S. E. H. (1999). Cytosol-to-lysosome transport of free polymannose-type oligosaccharides. Kinetic and specificity studies using rat liver lysosomes. J Biol. Chem. 274, 13547-13555. 

Collins, C.A. Wells, W.W. Identification of phosphatidyhnositol kinase in rat liver lysosomal membranes. J. Biol. Chem., 258, 2130-2134 (1983)... 

Table 34.2 Degradation of HPMA copolymers by rat liver lysosomal enzymes, effect of peptidyI side-chain...

Vercauteren, R., Schacht, E. and Duncan, R. (1992) Effect of the chemical modification of dextran on the degradation by rat liver lysosomal enzymes. J. Bioact. Biocomp. Polym. 7 346-357. 

Yanagita T, Enomoto N, Kuzuhara S. 1986. Effects of phthalate esters on liver lysosomal acid lipase and acid esterase in vitro. Agric Biol Chem 50 1653-1654. 

The pharmacokinetics of (+)-tubocurarine in man with and without renal failure, and anaesthetized with halothane and nitrous oxide, have been studied. Other studies with (+)-tubocurarine include investigations of its effects on neurally evoked compound electromyograms, its actions at hyperbaric pressures, the effects of circulating residue of the ED50 dose five minutes after injection on unexposed neuromuscular junctions, the uptake of (+)-tubo-curarine by liver lysosomes, the potentiation of (+)-tubocurarine neuromuscular blockade by lithium chloride in cats, effects on the heart and on ocular function, and the distribution of the alkaloid in cerebrospinal fluid after intravenous injection. The clinical pharmacology of dimethyl-(+)-tubocurarine (metocurine) has also been studied. ... 

Tin is an essential nutrient for growth in the rat, and a tin-deficient diet leads to reduced growth. The mechanism of action is unclear, but involves increasing metabolic activity of liver lysosomes and liver hydrolytic enzymes during regeneration. 

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