Under the supervision of: Dr- Nevert Faried Abdelsalam Researchers:

91-Esraa Raafat Ahmed Ahmed92-Esraa Reda Hashem Tewfik93-Esraa Samy Faried Abdelghafaar94-Esraa Saad Abaas Hamed95-Esraa Shawkey Abdelhak Abolaban

96-Esraa Sobhi Mohammed Abdelazez Histology Department

Faculty of Medicine Ain Shams University

Lysosomes

Introduction

-Lysosomes are spherical membranous vesicles containing numerous hydrolytic enzymes.-They had been discovered by Christian de duve.

-They are numerous in macrophages .-They can be demonstrated by “acid

phosphatase technique “ -Lysosomes act as disposal system of the cell

-Any malfunctioning of the lysosomes or any of the digestive proteins, results in lysosomal storage diseases.

Lysosomes are membrane bound organelles that are found in the cytoplasm of both plant and animal cells. The word lysosome was derived from two Greek words, 'lysis' which means destruction or dissolution and 'soma' which means 'body'. Lysosomes were discovered in 1949, by a Belgian cytologist, Christian de Duve.

Definition

Lysosome was discovered by christian de duve and his team . They described the lysosome as a "saclike structure surrounded by a membrane and containing acid

phosphatase".

Discovery

Lysosomes are organelles found in cytoplasm of the cell . They vary in number in different cells . They are numerous in macrophages.

Site

Lysosomes can’t be distinguished by H&E ordinary stain . They can be demonstrated by histochemical staining methods “ acid phosphatase technique “ since they are studded with acid hydrolases enzymes.

appearance LM

Lysosomes are spherical membrane bound vesicles

EM appearance

Lysosomes are manufactured by the Golgi apparatus, by budding, in the cell and the various digestive enzymes, that are present in the lysosomes are produced in the endoplasmic reticulum. These enzymes are then transported to the Golgi apparatus and are distributed to the lysosomes.

Formation

A lysosome that is newly produced from the golgi apparatus and hasn't yet performed any digestive function is called " primary lysosome" . Primary lysosomes have homogenous electron dense content ( low acidic pH ) . Once primary lysosome has entered digestive event by fusing with either phagosome or autophagosome or pinocytotic vesicle , A new structure is produced which is called " secondary lysosome". Secondary lysosomes are heterogeneous vesicles ( relatively high pH)

.Structure

Lysosomes are actually membranous sacs filled with enzymes. They are found in all eukaryotic cells and act as 'garbage disposal' or the 'digester' of the cell. Lysosomes are spherical bag like structures that are bound by a single layer membrane, however, the lysosome shape and size may vary to some extent in different organisms. The lysosome size ranges between 0.1 to 1.2μm. The membrane that surrounds the lysosome, protects the rest of the cell from the hydrolytic or digestive enzymes that are contained in the lysosomes

Some examples of enzymes present in the lysosomes include nucleases, proteases, lipases and carbohydrases. These enzymes are used to dissolve nucleic acids, proteins, lipids and carbohydrates, respectively. All these enzymes are typically hydrolytic and can digest cellular macromolecules. Lysosomes are acidic, with a pH of 4.8. This acidic pH is maintained by pumping protons, from the cytosol that has a pH of 7.2. The protons are pumped across the membrane via proton pumps and chloride ion channels. The membrane thus acts as a protective barrier, that protects the cytosol and the rest of the cell from the hydrolytic enzymes within the lysosome.

Lysosomes act as disposal system of the cell. They break down complex proteins, carbohydrates, lipids and other macromolecules into simpler compounds. These simple compounds are returned to the cytoplasm and are used as new cell building materials. They are used for digestion of cellular waste products, dead cells or extracellular material such as foreign invading microbes, that pose a threat to the cell by phagocytosis process. However, phagocytosis is just one process that helps to get rid of unwanted material in the cell. Lysosomes are also involved in other digestive processes including endocytosis and autophagy. Another interesting function of the lysosomes is to repair the damage to the plasma membrane. They serve as membrane patch and help in sealing the wound in the plasma membrane. Lysosomes are also involved in programmed cell death, or autolysis, which is a catabolic process involving degradation of the cell's own components. This is the reason why lysosomes are often known as 'suicide sacs'

Function

Lysosomes are enclosed by a single-layer membrane that allows the remainder of the cell to be protected from the harsh digestive enzymes that lysosomes use to break down and rid the cell of unwanted materials. This membrane also allows the lysosome to maintain an acidic environment similar to that of the stomach that aids in this same digestion.

structure correlated function

Any malfunctioning of the lysosomes or any of the digestive proteins, results in lysosomal storage diseases, such as Tay-Sachs disease and Pompe's disease. These diseases are caused by defective function of the lysosomes or in absence of any of the digestive proteins or lysosomal hydrolytic enzymes.

Defects .... Medical application

Lysosomal storage diseases describe a heterogeneous group of dozens of rare inherited disorders characterized by the accumulation of undigested or partially digested macromolecules, which ultimately results in cellular dysfunction and clinical abnormalities. Organomegaly, connective-tissue and ocular pathology, and central nervous system dysfunction may result. Classically, lysosomal storage diseases encompassed only enzyme deficiencies of the lysosomal hydrolases. More recently, the concept of lysosomal storage disease has been expanded to include deficiencies or defects in proteins necessary for the normal post-translational modification of lysosomal enzymes (which themselves are often glycoproteins), activator proteins, or proteins important for proper intracellular trafficking between the lysosome and other intracellular compartments.

Pompe disease is a glycogen storage disease. This rare inherited metabolic disorder is caused by an inborn lack of the enzyme alpha-1,4 glucosidase which is necessary to break down glycogen, . This enzyme deficiency causes excess amounts of glycogen to accumulate in the lysosomes .This may lead to severe muscle weakness and abnormally diminished muscle tone (hypotonia) without muscle wasting,Additional abnormalities may include enlargement of the heart(cardiomegaly), the liver (hepatomegaly), and/or the tongue (macroglossia)

Pompe disease (Genetic )

Myeloperoxidase (MPO) is a human enzyme in the azurophilic granules of neutrophils and in the lysosomes of monocytes. Its major role is to aid in microbial killing. Some patients with MPO deficiency have impaired microbial killing, but most are asymptomatic

Myeloperoxidase deficiency

Nephropathic cystinosis is an inherited (autosomal recessive) lysosomal storage disorder caused by defective transport of the amino acid cystine out of lysosomes. The stored cystine is poorly soluble and crystallizes within the lysosomes of many cell types, leading to widespread tissue and organ damage.

Cystinosis

Summary

In the Lysosomes, or Recycling Center of the Cell, our Penguins work hard and efficiently to move large bags of undegraded compounds, or substrates (denoted by the "S" on each bag). Each bag is broken down and sent back toIn the Lysosomes, or Recycling Center of the Cell, our Penguins work hard and efficiently to move large bags of undegraded compounds, or substrates (denoted by the "S" on each bag). Each bag is broken down and sent back to the body to be reused. the body to be reused.

In some people, our penguins can't do their job efficiently because of a genetic defect that prevents the bags of waste from moving through the Recycling Center. Most commonly, this defect is found in the enzyme whose job it is to bust up certain bags of substrates. The result is a slowdown in the workflow, resulting in substrates not moving through the Lysosome

Over time work in the Recycling Center comes to a virtual standstill and the bags of substrates begin to build up in the Lysosomes. When this happens the person affected displays a multitude of symptoms that cause pain, neurological damage and a shortened lifespan

References

NCBI Bookshelf.htm Medscape

Wikipedia Buzzle

WebMD