LYSOSOMES, HISTORY, OCCURRENCE, STRUCTURE, ENZYMES AND POLYMORPHISM

What is lysosomes ..............? 

 The lysosomes (Gr., lyso=digestive + soma=body) are tiny membrane-bound vesicles involved in intracellular digestion. They contain a variety of hydrolytic enzymes that remain active under acidic conditions. 

 Image :- Lysosome

HISTORY :- 

During early electron microscopic studies, rounded dense 0bodies were observed in rat liver cells. These bodies were initially described as “perinuclear dense bodies”. 

- C. de Duve, in 1955, renamed these organelles as ‘lysosomes’ to indicate that the internal digestive enzymes only became apparent when the membrane of these organelles was lysed (See Reid and Leech, 1980). 

- The term lysosome means lytic body having digestive enzymes capable of lysis (viz., dissolution of a cell or tissue; (De Robertis and De Robertis, Jr., 1987). 

Lysosomes were investigated according to following two schools : 

(1) C. de Duve and his coworkers (1963, 1964, 1974) worked in Belgium and their approach was biochemical one. 

(2) Alex Novikoff and his research group (1962, 1964) worked in United States and their approach was morphological and cytochemical. 

- For the discovery of lysosomes and a brilliant series of experiments on them, de Duve shared the 1974 Nobel Prize for physiology with Palade and Claude, both were pioneer cell biologists.

OCCURRENCE :- 

- The lysosomes occur in most animal and few plant cells . They are absent in bacteria and mature mammalian erythrocytes. 

- Few lysosomes occur in muscle cells or in acinar cells of the pancreas. Leucocytes, especially granulocytes are a particularly rich source of lysosomes. Their lysosomes are so large-sized that they can be observed under the light microscope.

- Lysosomes are also numerous in epithelial cells of absorptive, secretory and excretory organs (e.g., intestine, liver, kidney, etc.). They occur in abundance in the epithelial cells of lungs and uterus.

- Phagocytic cells and cells of reticuloendothelial system (e.g., bone marrow, spleen and liver) are also rich in lysosomes.

STRUCTURE :- 

The lysosomes are round vacuolar structures which remain filled with dense material and are bounded by single unit membrane. 

Their shape and density vary greatly. Lysosomes are 0.2 to 0.5μm in size. Since, size and shape of lysosomes vary from cell to cell and time to time (i.e. they are polymorphic), their identification becomes difficult. 


However, on the basis of the following three criteria, a cellular entity can be identified as a lysosome:

 (1) It should be bound by a limiting membrane;

(2) It should contain two or more acid hydrolases; 

(3) It should demonstrate the property of enzyme latency when treated in a way that adversely affects organelle’s membrane structure

Examples of plant and animal cells, tissues and organs containing lysosomes-

A. Animal tissues

1. Liver

2. Kidney

3. Nerve cells

4. Brain

5. Intestinal epithelium

6. Lung epithelium

7. Macrophages

(of spleen, bone marrow, liver and

connective tissue)

8. Thyroid gland

9. Adrenal gland

10. Bone

11. Urinary bladder

12. Prostate

13. Uterus

14. Ovaries

B. Protozoa

15. Leucocytes

16. Amoeba

17. Tetrahymena

18. Paramecium

19. Euglena

C. Plants

20. Onion seeds

21. Barley seeds

22. Corn seedlings

23. Yeast

24. Neurospora

D. Tissue culture cells

25. HeLA cells

26. Fibroblasts

27. Chick cells

28. Lymphocytes

Lysosomal Enzymes :- 

- According to a recent estimate,a lysosome may contain up to 40 types of hydrolytic enzymes (see Alberts et al.,1989). 

- They include proteases (e.g., cathepsin for protein digestion), nucleases, glycosidases (for digestion of polysaccharides and glycosides), lipases, phospholipases, phosphatases and sulphatases (Table 8-2).

- All lysosomal enzymes are acid hydrolases, optimally active at the pH5 maintained within lysosomes. 

- The membrane of the lysosome normally keeps the enzymes latent and out of the cytoplasmic matrix or cytosol (whose pH is about ~7.2), but the acid dependency of lysosomal enzymes protects the contents of the cytosol (cytoplasmic matrix) against any damage even if leakage of lysosomal enzymes should occur.

Some lysosomal enzymes and their substrates :- 

A. Proteases and peptidases

1. Cathepsin A,B,C,D and E

2. Collagenase

3. Peptidases

B. Nucleases

4. Acid ribonuclease

5. Acid deoxyribonuclease

C. Phosphatases

6. Acid phosphatase

7. Phosphodiesterase

D. Enzymes acting on oligosaccharide

chains of glycoproteins and glycolipids

8. b-galactosidase

9. Acetylhexosaminidase

10. b-Glucosidase

11. a- Glucosidase

12. a-Mannosidase

13. Sialidase

E. Enzymes acting on glycosaminoglycans

14. Lysozyme

15. Hyaluronidase

16. b-Glucuronidase

F. Enzymes acting on lipids

17. Phospholipase

18. Esterase

KINDS OF LYSOSOMES (POLYMORPHISM IN LYSOSOMES) :- 

Lysosomes are extremely dynamic organelles, exhibiting polymorphism in their morphology. 

Following four types of lysosomes have been recognized in different types of cells or at different times in the same cell. Of these, only the first is the primary lysosome, the other three have been grouped together as secondary lysosomes.

1. Primary Lysosomes :- 

These are also called storage granules, protolysosomes or virgin lysosomes. Primary lysosomes are newly formed organelles bounded by a single membrane and typically having a diameter of 100 nm. 

They contain the degradative enzymes which have not participated in any digestive process. Each primary lysosome contains one type of enzyme or another and it is only in the secondary lysosome that the full complement of acid hydrolases is present.

2. Heterophagosomes :- 

They are also called heterophagic vacuoles, heterolysosomes or phagolysosomes. Heterophagosomes are formed by the fusion of primary lysosomes with cytoplasmic vacuoles containing extracel lular substances brought into the cell by any of a variety of endocytic processes (e.g., pinocytosis, phagocytosis or receptor-mediated endocytosis ). 

The digestion of engulfed substances takes place by the enzymatic activities of the hydrolytic enzymes of the secondary lysosomes. The digested material has low molecular weight and readily passess through the membrane of the lysosomes to become the part of the matrix.

3. Autophagosomes :- 

- They are also called autophagic vacuole, cytolysosomes or autolysosomes. Primary lysosomes are able to digest intracellular structures including mitochondria, ribosomes, peroxisomes and glycogen granules. 

 - Such autodigestion (called autophagy) of cellular organelles is a normal event during cell growth and repair and is especially prevalent in differentiating and dedifferentiating tissues (e.g., cells undergoing programmed death during metamorphosis or regeneration) and tissue under stress. 

 - The inner membrane then breaks down and the enzymes are able to penetrate to the enclosed organelle.In other cases, the organelle to be digested is first encased by smooth ER, forming a vesicle that fuses with a primary lysosome .

-  Lysosomes also regularly engulf bits of cytosol (cytoplasmic matrix) which is degraded by a process, called microautophagy.

4. Residual Bodies :- 

- They are also called telolysosomes or dense bodies. Residual bodies are formed if the digestion inside the food vacuole is incomplete.

Incomplete digestion may be due to absence of some lysosomal enzymes. 

- The undigested food is present in the digestive vacuole as the residues and may take the form of whorls of membranes, grains, amorphous masses, ferritin-like or myelin.

FUNCTIONS OF LYSOSOMES :- 

1. Digestion of large extracellular particles.

 The lysosomes digest the food contents of the phagosomes or pinosomes. The lysosomes of leucocytes enable the latter to devour the foreign proteins, bacteria and viruses.

2. Digestion of intracellular substances. 

During the starvation, the lysosomes digest the stored food contents, viz., proteins, lipids and carbohydrates (glycogen) of the cytoplasm and supply to the cell neccessary amount of energy.

3. Autolysis.

 In certain pathological conditions the lysosomes start to digest the various organelles of the cells and this process is known as autolysis or cellular autophagy.

- When a cell dies, the lysosome membrane ruptures and enzymes are liberated. These enzymes digest the dead cells. In the process of metamorphosis of amphibians and \tunicates many embryonic tissues, e.g., gills, fins, tail, etc., are digested by the lysosomes and utilized by the other cells.

4. Extracellular digestion. 

The lysosomes of certain cells such as sperms discharge their enzymes outside the cell during the process of fertilization. 

The lysosomal enzymes digest the limiting membranes of the ovum and form penetration path in ovum for the sperms. 

Acid hydrolases are released from osteoclasts and break down bone for the reabsorption; these cells also secrete lactic acid which makes the local pH enough for optimal enzyme activity. 

Likewise, preceding ossification (bone formation), fibroblasts release cathepsin D enzyme to break down the connective tissue











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