In quick review, we have discussed the cell membrane, membrane bound proteins, cytoskeleton, endoplasmic reticulum, Golgi apparatus, vesicles and vacuoles.  We have seen how complicated and specific they are and how they interact with each other.  This week, we are going to take a look at lysosomes.

Lysosomes, first discovered in 1955, are membrane bound organelles found in the cytoplasm of eukaryote cells (cells with a nucleus).  If you recall in Part 1 of this series, cells have a double layer or bilipid membrane.  Lysosomes have a single layer membrane.  Their shape and size can vary.  The internal matrix of the lysosome contains hydrolytic enzymes and is highly acidic with a pH around 4.8.  If for any reason the lysosome membrane ruptures and releases its acidic contents into the cellular cytoplasm, the neutrality of the cytoplasm instantly dilutes and neutralizes the acids to prevent any harm to the rest of the cell.

Lysosomes have several important functions within the cell.

Stomach

One of those functions is to serve as the stomach for the cell.  As food particles are brought into the cell in vacuoles.  The vacuoles transfer the food particles to the lysosome where they are broken down into the necessary nutrients and compounds to be used by other cell structures.  What ever is not consumed by the other organelles is packaged back into a vacuole which transports the waste material to the cell membrane where it is excreted from the cell.

Garbage Disposal

As we have seen in previous installments in this series, there are literally hundreds of different processes and manufacturing of proteins, and other molecules throughout the cell.  Not unlike our manufacturing industries, there is a certain amount of waste and by-products produced.  These by-products are collected by vesicles and vacuoles from throughout the cells and transported to the lysosomes where the by-products are broken down.

Recycle Center

When the waste and by-products from the cell are brought to the lysosome, they are broken down by up to 40 different enzymes contained in the lysosomal matrix.  These enzymes are manufactured in the endoplasmic reticulum and passed through the Golgi apparatus.  As they reach the trans-Golgi, they bud off from the Golgi membrane to form the lysosome.  Depending on which hydrolytic enzyme the lysosome contained, will determine exactly how the lysosome handles the cellular by-products.  The lysosomes then break down the cellular waste products such as fats (lipids), carbohydrates, proteins, and other macromolecules into simple compounds, which are then returned to the cell as new cell-building materials.  Only those waste products that can no longer be used are then transported back outside the cell for excretion.

Immune Defense

Whenever pathogens such as bacteria enter the cell, lysosomes are dispatched.  They lysosome attacks the bacteria and engulfs it so that its acidic matrix can break down and destroy the bacteria.  This is why there are so many lysosomes in leukocytes (white blood cells).  They play a very important role in our immune defense system.

Lysosomal Storage Disorders (LSDs)

From time to time, someone will have a genetic mutation that results in the inability for the cells to produce one or more of the 40 different enzymes used in the lysosomes.  Without these specific enzymes, the lysosome cannot properly process the various materials brought to it.  If the lysosome is unable to process a certain substance, that substance will begin to accumulate in the cell, causing a number of different disorders and diseases.

The first disease to be identified as an LSD was Pompe disease in 1960.  Pompe disease is caused by a mutation that results in the cell’s inability to produce an enzyme called alpha-glucosidase (GAA).  To date, researchers have identified nearly 70 different mutations that cause varying symptoms and degrees of Pompe disease.  GAA normally breaks down glycogen which is a form of sugar that the body stores.  As the excess glycogen builds up in the body, it starts to affect the skeletal muscles and the heart.  The onset of Pompe disease can vary in terms of age and severity of the symptoms.  Those individuals that exhibit early onset Pompe from birth rarely live to their first birthday and succumb from cardiac failure.  Later onset of Pompe can be treated with an enzyme replacement therapy.  If left untreated, the disease can be fatal as it will eventually interfere with the ability of the heart and skeletal muscles to function properly.

Another well known LSD is Tay-Sachs Disease.  Tay-Sachs is caused by a mutation that affects the ability to produce the enzyme beta-hexosaminidase A. This results in the lysosome’s inability to break down a fatty substance called Ganglioside M2.  The incidence of Tay-Sachs is particularly high among people of Eastern European and Askhenazi Jewish descent.  For a person to develop Tay-Sachs, they have to receive the mutated gene from both parents.  If both parents carry the defective gene there will be a 25% chance that their children will develop the disease.   Generally, an infant born with Tay-Sachs will appear and develop normally for the first few months.  As the GM2 begins to build up it collects around never tissue throughout the body and in the brain, which causes the nerve cells to become enlarged.  As the nerves enlarge with the build up of GM2 it causes increased symptoms of muscle atrophy leading to paralysis, blindness, deafness, the inability to swallow, seizures, dementia and an increase in the startle response to noise.  The majority of children with Tay-Sachs die before their 4th birthday.  To date there is no known cure for Tay-Sachs disease.

Since the discovery of the first LSD in 1960, there have been a number of other LSDs discovered.  They are generally divided into 8 categories based upon the type of enzyme deficiency that is interfering with the normal cellular activity.

These groups and their associated diseased are:

Defective metabolism of glycosaminoglycans

(also known as the “mucopolysaccharidoses”)

MPS I;  MPS II; MPS III; MPS IV; MPS VI; and MPS VII

Defective degradation of glycan portion of glycoproteins

Aspartylglucosaminuria; fucosidosis, type I; fucosidosis, type II; mannosidosis; sialidosis, type I; and sialidosis, type II

Defective degradation of glycogen

Pompe disease

Defective degradation of sphingolipid components

acid sphingomyelinase deficiency; Fabry disease; Farber disease; Gaucher disease, type I; Gaucher disease, type II; Gaucher disease, type III; GM1 gangliosidosis, type I; GM1 gangliosidosis, type II; GM1 gangliosidosis, type III; Tay-Sachs disease, type I; Tay-Sachs disease, type II; Tay-Sachs disease, type III; Sandhoff disease; Krabbé disease; metachromatic leukodystrophy, type I; metachromatic leukodystrophy, type II; metachromatic leukodystrophy, type III

Defective degradation of polypeptides

pycnodysostosis

Defective degradation or transport of cholesterol, cholesterol esters, or other complex lipids

neuronal ceroid lipofuscinosis, type I; neuronal ceroid lipofuscinosis, type II; neuronal ceroid lipofuscinosis, type III; neuronal ceroid lipofuscinosis, type IV

Multiple deficiencies of lysosomal enzymes

Galactosialidosis; mucolipidosis II; mucolipidosis III

Transport and trafficking defects

Cystinosis; mucolipidosis IV; infantile sialic acid storage disease (ISSD); Salla disease

When the lysosomes are working properly, they function as the stomach, garbage disposal, recycling center and immune defense systems, all of which are very important roles.  When the lysosomes are not working properly as the result of a number of possible genetic mutations, it can cause a myriad of diseases, some of which are incurable and fatal.

Without the lysosome, there is no way an organism could survive long enough to reproduce itself.  I wonder from what non-living group of prebiotic goop was suppose to be the precursor for what eventually evolved into the lysosome.  If you tried to calculate the mathematical probability of the lysosome and all 40 of the enzymes it needs to function properly to have evolved all at the same time, it would be as near to 0 as possible

Lysosomes are another miraculous creation of our creator God and testimony to His Creation.

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