Function of Lysosomes

The importance of lysosomes in physiopathological autolysis, intracellular digestion and engulfing processes was pointed out by de Duve (D7, D8) and Novikoff (N5). Within recent years several studies have appeared in which the actions of purified lysosomal preparations on proteins, carbohydrates and lipids have been considered (A14, C5, M3, S2). 

Sawant ef al. (S2) studied the digestion of rat liver homogenate, mitochondria, microsomes, and nuclei by a purified preparation of lysosomes. A few values, particularly for inorganic phosphate, may be quoted to show the extent of digestion at 37°C and pH 7.0. With regard to the action on liver homogenate, 1 rag of lysosomal protein formed 28 and 38 nmoles of amino acids and peptides in 0.5 hour and 3.0 hours. 

The formation of inorganic phosphate was, of course, a manifestation of phosphatase action. In this connection, two features were of interest. First, in the mitochondrial degradation by lysosomes, the rate of formation of inorganic phosphate decreased from values of about 2 imoles in 30 minutes at pH of 4-5 to a value of about 0.6 /xmole in 30 minutes at pH 6.0, then rose again to about 2 units at pH s of 7 to 9. Second, tartrate and fluoride were potent inhibitors 2.5 X 10 M tartrate decreased the rate of release to 21% of the control value, and 1 X 10 M inhibited the formation completely. Fluoride had a similar effect. 

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The lysosomes are the cell s stomach, serving to break down various cell components. For this purpose, they contain some 40 different types of hydrolases, which are capable of breaking down every type of macromolecule. The marker enzyme of lysosomes is acid phosphatase. The pH optimum of lysosomal enzymes is adjusted to the acid pH value and is also in the range of pH 5. At neutral pH, as in the cytoplasm, lysosomal enzymes only have low levels of activity. This appears to be a mechanism for protecting the cells from digesting themselves in case lysosomal enzymes enter the cytoplasm at any time. In plants and fungi, the cell vacuoles (see p. 43) have the function of lysosomes. 

The answer is D. As this patient ages, a variety of skeletal defects and short stature that are consistent with a lysosomal storage disease (mucolipidosis), either I-cell disease or pseudo-Hurler polydystrophy, are developing. Both diseases arise from a deficiency of an enzyme involved in synthesis of the Man-6-P marker on lysosomal enzymes. Such misaddressed proteins are secreted rather than trafficked to the lysosomes. The degradative function of lysosomes is impaired as a result and the organelles tend to accumulate waste products (hence, the term storage disease ). It is these inclusion bodies or dense structures that would be visible by microscopic examination of the patient s cells in a biopsy specimen. 

Hydroxychloroquine and chloroquine are similar in activity however, hydroxychloroquine has a lower incidence of ocular side effects and is used more frequently. These drugs are weak bases that enter and interfere with the functioning of lysosomes and other subcellular compartments of T- and B-lymphocytes, monocytes, and macrophages. This in turn inhibits the ability of these cells to produce and release inflammatory cytokines and hydrolytic enzymes. 

The most clearly documented role lor selenium is as a necessary component of glutathione peroxidase. Selenium is also involved in the functions of additional enzymes, e.g.. type I iodoihvronine deiodinase. leukocyte acid phosphatase, and glucuronidases. A role for selenium in electron transfer has been suggested as has involvement in nonheme iron proteins. Selenium and vitamin b appear to be necessary lor proper functioning of lysosomal membranes. A role for selenium in metabolism of thyroid hormone has been continued. 

DeDuve C, Wattiaux R. Functions of lysosomes. Annu. Rev. Physiol. 1966 28 435-492. 

The function of lysosomes is intracellular and extracellular digestion. These spherical, membranous organelles contain a group of enzymes called acid hydrolases, which degrade most biomolecules. 

Structures and Functions of Lysosomal Thiol Proteinoses and Their Endogenous Inhibitor... 

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