Structural Biochemistry/Cell Organelles/Lysosome

Lysosome
Lysosomes are spherical bodies, or vacuoles that are enclosed by a single membrane. The membrane serves as a protectorate to the cell, since lysosomes contain harsh digestive enzymes, which would cause significant damage if exposed to cell content. Lysosomes contain different hydrolytic enzymes, such as proteases, lipases, and nucleases that are capable of breaking down all types of biological polymers (e.g. proteins, nucleic acids, carbohydrates, and lipids) that enter the cell or are no longer useful to the cell. In all, lysosomes function as the digestive system of the cell. On another note, lysosomes avoid self-digestion by glycosylation of inner membrane proteins, which prevent their degradation.

Lysosomes are membrane-enclosed organelles that help eukaryotic cells obtain nourishment from macromolecular nutrients. The lysosomes contain many hydrolytic enzymes such as proteases, nucleases, and lipases). The lysosomes are formed vesicles containing hydrolytic enzymes and proton pumps bud off from the Golgi complex. Phagocytosis and lysosomal digestion help the eukaryotic cell because they effectively increase the membrane surface area over which nutrients can be absorbed. However, in eukaryotes, lysosomes allow for intracellular digestion, and digested material crosses the lysosomal membrane into the cytoplasm.

Lysosome Production
Lysosomes are manufactured and budded into the cytoplasm by the Golgi apparatus with enzymes inside. The enzymes that are within the lysosome are made in the rough endoplasmic reticulum, which are then delivered to the Golgi apparatus via transport vesicles. When lysosome reaches the cytoplasm, fusion forms a secondary lysosome.

Inside Lysosomes
Lysosomes contain enzymes that include:
 * Glycosidase: an enzyme that catalyzes the hydrolysis of glycosidic linkages in sugar molecules.
 * Protease: an enzyme that catalyzes the hydrolysis of peptide bonds.
 * Acid phosphatase: a phosphatase, an enzyme that catalyzes they hydrolysis of phosphate linkages in a variety of molecules.
 * Sulfatase: an enzyme that catalyzes the hydrolysis of sulfate ester linkages in molecules.
 * Lipase: an enzyme that catalyzes the hydrolysis of ester bonds in lipid molecules.
 * Amylase: an enzyme that catalyzes the breakdown of carbohydrates into sugars.
 * Nuclease: an enzyme that catalyzes the hydrolysis of phosphodiester bonds in nucleotide subunits of nucleic acids. Lysosome.jpg
 * Glucocerebrosidase: an enzyme which breaks down glucocerebroside
 * Phosphoric Acid monoesters

Lysosome enzymes are proteins that are synthesized in the endoplasmic reticulum and modified in the Golgi apparatus. Lysosomal enzymes are tagged for lysosomes by the addition of mannose-6-phopahte label. A shortage of any one of these enzymes will lead to lysosome diseases such as Tay-Sachs disease and Pompe’s disease.

Lysosomal Defects
In human cells, when lysosomes lack enzymes they can generate storage disease. People with these defects are usually missing one or more of the Lysosomal hydrolysis enzymes.
 * Tay-Sachs Disease
 * Tay-Sachs disease is a disease that affects the nervous system. It occurs when the body lacks hexosaminidase A, a protein that breaks down ganglioside. Accumulation of ganglioside
 * Pompe’s disease
 * Pompe’s disease is a disease that affects the heart Lysosome.jpg skeletal muscles. It occurs when the body lacks alpha-glucosidase, an enzyme that breaks down glycogen.
 * Mucopolysaccharidosis I
 * MPS I is cause by the deficiency of the lysosomal enzyme alpha-L-iduronidase. Deficiency can effect both skeletal and mental development.
 * Gaucher’s disease
 * Gaucher’s disease is caused by the deficiency of the lysosomal enzyme glucocerebrosidase enzyme. A deficiency of this enzyme causes harmful substances to build up in liver, spleen, bones, and bone marrow.

Lysosomal Enzyme Production
Enzymes that are used by the lysosome are synthesized in the endoplasmic reticulum (ER) and are transported to the Golgi apparatus (GA). The ER formed transport vesicles that carry the enzymes and loads them by fusing them to the GA. Glycosylation may occur, which will determine the final destination of the proteins.

Lysosome Acid-Hydrolyses
Lysosomes contain a variation of enzymes that hydrolyze proteins, nucleic acids, carbohydrates, and lipids. The enzymes present in the lysosomes work best at an acidic pH; thus they are referred to as acid hydrolases. Is it evident to note that the pH in a lysosome is about ~5 while the cytoplasm has a neutral pH of about ~7. In order for the lysosome to maintain an acidic pH, the lysosome must actively uptake concentrate H+ ions (protons). The concentrated H+ ions are actively equilibrated to reach a pH of about 5 by hydrogen ion pumps. In part with the pH level, enzymes within a lysosomes work best at an acidic pH.

Function
Lysosomes digest unused and/or threatening content that is present in the cell. In retrospect, lysosomes recycle the cell’s organic material in a process known as autophagy. It also recycles waste products such as fats, carbohydrates, proteins, and other macromolecules into simple compounds, which are then utilized as new materials in the cytoplasm. The recycling of waste product is in large part due to about 40 different types of hydrolytic enzymes that are engineered by the endoplasmic reticulum and modified by the Golgi apparatus.


 * Autophagy (Autophagocytosis)
 * The term autophagy is derived from the Greek “auto” or oneself and “phagy” to eat. Autophagy is a process of self-eating and self-degradation. The degradation takes part when the cell content and organelles is consumed by lysosomes. The cell produces vesicles called autophagosomes that captures and deliver cytoplasmic material to lysosomes. Autophagosomes are formed when the ER wraps around damaged cell structures or cell content, of which the lysosome then joining the autophagosomes to destroy the content captured and delivers the broken down material to the cytoplasm. Overall, autophagocytosis preserves the health of cells and tissues by degrading unused and/or damaged cellular content to new ones.


 * Endocytosis
 * Endocytosis occurs when the cell membrane of a cell surrounds large nutritional molecules. This engulfing of a large nutritional molecule forms a endosome. Some of the things endosomes acquire are complex lipids, polysaccharides, nucleic acids, and proteins. Lysosomes then fuse with endosomes, whereby it transfers it enzymes to breakdown molecules. The broken down molecules are then delivered to the cytoplasm by proteins for later consumption.


 * Phagocytosis
 * Lysosome works in close relations with phagocytosis whereby it joins phagosomes to break down the object or bacteria with its enzymes. Phagosomes are produced when the cell membrane of a cell surrounds a disease-causing bacterium; toxic or unused content in/outside the cell.