Lysosomal digestion

Cathepsin D Spleen, liver, and many other animal tissues Lysosomal digestion of proteins... 

The more acidic late endosomes (pH ca. 5.5 or less) are sometimes referred to as pre-lysosomes. Digestion of the food material or other macromolecules... 

Endocytosis involves the ceUular uptake of exogenous molecules or complexes inside plasma membrane-derived vesicles. This process can be divided into two major categories (1) adsorptive or phagocytic uptake of particles that have been bound to the membrane surface and (2) fluid or pinocytotic uptake, in which the particle enters the cell as part of the fluid phase. The solute within the vesicle is released intracellularly, possibly through lysosomal digestion of the vesicle membrane or by intermembrane fusion (Fig. 3.4). 

In addition to their plasma membrane eukaryotic cells also contain internal membranes that define a variety of organelles (fig. 17.2). Each of these organelles is specialized for particular functions The nucleus synthesizes nucleic acids, mitochondria oxidize carbohydrates and lipids and make ATP, chloroplasts carry out photosynthesis, the endoplasmic reticulum and the Golgi apparatus synthesize and secrete proteins, and lysosomes digest proteins. Additional membranes divide mitochondria and chloroplasts into even finer, more specialized subcompartments. Like the plasma membrane, organellar membranes act as barriers to the leakage of proteins, metabolites, and ions they contain transport systems for import and export of materials, and they are the sites of enzymatic activities as diverse as cholesterol biosynthesis and oxidative phosphorylation. 

Drug molecule dissolved in the extracellular fluid Lysosomal digestive enzymes... 

A family of intracellular thiol proteases involved in lysosomal digestion of proteins. See Janoff, A., Mediators of tissue damage in human polymorphonuclear neutrophils, Sen Haematol. 3, 96-130, 1970 Harris, E.D., Jr. and Krane, S.M., Collagenases, N. Engl. J. Med. 291, 605-609, 1974 Larzarus, G.S., Hatcher, V.B., and Levine, N., Lysosomes and the skin,... 

Masquelier M, Baurain R, Trouet A. Amino acid and dipeptide derivatives of daunorubicin. 1. Synthesis, physicochemical properties, and lysosomal digestion. J Med Chem 1980 23 1166-1170. 

Lysosomes digest all types of biomolecules. In addition to the normal processing of cellular molecules, lysosomes also destroy the components of foreign cells and other exogenous extracellular materials. 

The lysosomal digestive enzymes include nucleases, phosphatases, glycosi-dases, esterases, and proteases called cathepsins (Fig. 10.15). These enzymes are all hydrolases, enzymes that cleave amide, ester, and other bonds through the addition of water. Many of the products of lysosomal digestion, such as the amino acids, return to the cytosol. Lysosomes are therefore involved in recycling compounds. 

Cholesterol is packaged in chylomicrons in the intestine and in very-low-den-sity lipoprotein (VLDL) in the liver. It is transported in the blood in these lipoprotein particles, which also transport triacylglycerols. the triacylglycerols of the blood lipoproteins are digested by lipoprotein lipase, chylomicrons are converted to chylomicron remnants, and VTDT is converted to intermediate-density lipoprotein (IDL) and subsequently to low-density lipoprotein (LDL). These products return to the liver, where they bind to receptors in cell membranes and are taken up by endocytosis and digested by lysosomal enzymes. LDL is also endocy-tosed by nonhepatic (peripheral) tissues. Cholesterol and other products of lysosomal digestion are released into the cellular pools. The liver uses this recycled cholesterol, and the cholesterol that is synthesized from acetyl CoA, to produce VLDL and to synthesize bile salts. 

Other lipoproteins and from cell membranes and converts it to cholesterol esters by the lecithin.-cholesterol acyltransferase (LCAT) reaction. Then HDL either directly transports cholesterol and cholesterol esters to the liver or transfers cholesterol esters to other lipoproteins via the cholesterol ester transfer protein (CETP) Ultimately, lipoprotein particles carry the cholesterol and cholesterol esters to the liver, where endocytosis and lysosomal digestion occur. Thus, reverse cholesterol transport (i.e., the return of cholesterol to the liver) is a major function of HDL. 

Lysosome Digestion of substances taken into ceUs... 

LaBadie, J., W.A. Dunn, and N.N. Jr. Aronson. 1976. Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-... 

Presence of abnormal amount of lipid in circulating blood Brown pigment granules lipid-containing residues of lysosomal digestion... 

More recent approaches to enhance transfection efficiency use fusogenic peptides to improve the performance. Such peptides help the DNA to escape lysosomic digestion in a similar manner as the capsid proteins do in the case of viruses. A conformational change is induced at low pH, which triggers a fusogenic activity. Typically such peptides contain virus derived amino acid sequences. 

In the next sections I shall consider some examples of biological processes in which cathepsin D seems to play a role, as judged by elevations in its activity and by other evidence pointing to the involvement of the lysosomal digestion mechanism within the cell. 

LaBadie, J. Dunn, W.A. Aronson, N.N. Jr. Hepatic Synthesis of Carnitine from Protein-Bound Trimethyl-Lysine. Lysosomal Digestion of Methyl-Lysine-Labelled Asialo-Fetuin. Bio-chem. J. 1976, 160, 85-95. 

Figure 1. Lysosomal Digestive Pathways for Glycosaminoglycans. Each structure represents a type of repeating unit in the particular polysaccharide. Enzyme names with corresponding numbers are given in Table 2. A slash between two enzyme numbers indicates either reaction can precede the other.

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