12 The endomembrane system
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A set of three major organelles together form a system within the cell called the endomembrane system. These organelles work together to perform various cellular jobs, including the task of producing, packaging, and exporting certain cellular products. The organelles of the endomembrane system include the endoplasmic reticulum, Golgi apparatus, and vesicles.
Endoplasmic reticulum
The endoplasmic reticulum (ER) is a system of channels that is continuous with the nuclear membrane (or “envelope”) covering the nucleus and composed of the same lipid bilayer material. The ER can be thought of as a series of winding thoroughfares like the waterway canals in Venice. The ER provides passages throughout much of the cell that function in transporting, synthesising, and storing materials. The winding structure of the ER results in a large membranous surface area that supports its many functions (Figure 3.8).
Endoplasmic reticulum can exist in two forms: rough ER and smooth ER. These two types of ER perform some very different functions and can be found in very different amounts depending on the type of cell. Rough ER (RER) is so-called because its membrane is dotted with embedded granules—organelles called ribosomes, giving the RER a bumpy appearance. A ribosome is an organelle that serves as the site of protein synthesis. It is composed of two ribosomal RNA subunits that wrap around mRNA to start the process of translation, followed by protein synthesis. Smooth ER (SER) lacks these ribosomes.
One of the main functions of the smooth ER is in the synthesis of lipids. The smooth ER synthesises phospholipids, the main component of biological membranes, as well as steroid hormones. For this reason, cells that produce large quantities of such hormones, such as those of the female ovaries and male testes, contain large amounts of smooth ER. In addition to lipid synthesis, the smooth ER also sequesters (i.e., stores) and regulates the concentration of cellular Ca2+, a function extremely important in cells of the nervous system where Ca2+ is the trigger for neurotransmitter release. The smooth ER additionally metabolises some carbohydrates and performs a detoxification role, breaking down certain toxins.
In contrast with the smooth ER, the primary job of the rough ER is the synthesis and modification of proteins destined for the cell membrane or for export from the cell. For this protein synthesis, many ribosomes attach to the ER (giving it the studded appearance of rough ER). Typically, a protein is synthesised within the ribosome and released inside the channel of the rough ER, where sugars can be added to it (by a process called glycosylation) before it is transported within a vesicle to the next stage in the packaging and shipping process: the Golgi apparatus.
The Golgi Apparatus
The Golgi apparatus is responsible for sorting, modifying, and shipping off the products that come from the rough ER, much like a post-office. The Golgi apparatus looks like stacked flattened discs, almost like stacks of oddly shaped pancakes. Like the ER, these discs are membranous. The Golgi apparatus has two distinct sides, each with a different role. One side of the apparatus receives products in vesicles. These products are sorted through the apparatus, and then they are released from the opposite side after being repackaged into new vesicles. If the product is to be exported from the cell, the vesicle migrates to the cell surface and fuses to the cell membrane, and the cargo is secreted (Figure 3.9).
Lysosomes
Some of the protein products packaged by the Golgi include digestive enzymes that are meant to remain inside the cell for use in breaking down certain materials. The enzyme-containing vesicles released by the Golgi may form new lysosomes, or fuse with existing, lysosomes. A lysosome is an organelle that contains enzymes that break down and digest unneeded cellular components, such as a damaged organelle. (A lysosome is like a wrecking crew that takes down old and unsound buildings in a neighbourhood.) Autophagy (“self-eating”) is the process of a cell digesting its own structures. Lysosomes are also important for breaking down foreign material, for example, when certain immune defence cells (white blood cells) phagocytose bacteria, the bacterial cell is transported into a lysosome and digested by the enzymes inside. As one might imagine, such phagocytic defence cells contain large numbers of lysosomes.
Under certain circumstances, lysosomes perform a more grand and dire function. In the case of damaged or unhealthy cells, lysosomes can be triggered to open up and release their digestive enzymes into the cytoplasm of the cell, killing the cell. This “self-destruct” mechanism is called autolysis, and makes the process of cell death controlled (a mechanism called “apoptosis”).
Organelles for the energy production and detoxification
In addition to the jobs performed by the endomembrane system, the cell has many other important functions. Just as you must consume nutrients to provide yourself with energy, so must each of your cells take in nutrients, some of which convert to chemical energy that can be used to power biochemical reactions. Another important function of the cell is detoxification. Humans take in all sorts of toxins from the environment and also produce harmful chemicals as by-products of cellular processes.
Cells called hepatocytes in the liver detoxify toxins.
Mitochondria
A mitochondrion (plural = mitochondria) is a membranous, bean-shaped organelle that is the “energy transformer” of the cell. Mitochondria consist of an outer lipid bilayer membrane as well as an additional inner lipid bilayer membrane (Figure 3.10). The inner membrane is highly folded into winding structures with a great deal of surface area, called cristae. It is along this inner membrane that a series of proteins, enzymes, and other molecules perform the biochemical reactions of cellular respiration. These reactions convert energy stored in nutrient molecules (such as glucose) into adenosine triphosphate (ATP), which provides usable cellular energy to the cell. Cells use ATP constantly, and so the mitochondria are constantly at work. Oxygen molecules are required during cellular respiration, which is why you must constantly breathe it in. One of the organ systems in the body that uses huge amounts of ATP is the muscular system because ATP is required to sustain muscle contraction. As a result, muscle cells are packed full of mitochondria. Nerve cells also need large quantities of ATP to run their sodium-potassium pumps. Therefore, an individual neuron will be loaded with over a thousand mitochondria. On the other hand, a bone cell, which is not nearly as metabolically active, might only have a couple hundred mitochondria.
Peroxisomes
Like lysosomes, a peroxisome is a membrane-bound cellular organelle that contains mostly enzymes (Figure 3.11). Peroxisomes perform a couple of different functions, including lipid metabolism and chemical detoxification. In contrast to the digestive enzymes found in lysosomes, the enzymes within peroxisomes serve to transfer hydrogen atoms from various molecules to oxygen, producing hydrogen peroxide (H2O2). In this way, peroxisomes neutralise poisons such as alcohol. In order to appreciate the importance of peroxisomes, it is necessary to understand the concept of reactive oxygen species.
Reactive oxygen species (ROS) such as peroxides and free radicals are the highly reactive products of many normal cellular processes, including the mitochondrial reactions that produce ATP and oxygen metabolism. Some ROS are important for certain cellular functions, such as cell signalling processes and immune responses against foreign substances. Free radicals are reactive because they contain free unpaired electrons; they can easily oxidise other molecules throughout the cell, causing cellular damage and even cell death.
For example
Examples of ROS include the hydroxyl radical OH, H2O2, and superoxide (O2−).
Peroxisomes oversee reactions that neutralise free radicals. Peroxisomes produce large amounts of the toxic H2O2 in the process, but peroxisomes contain enzymes that convert H2O2 into water and oxygen. These by-products are safely released into the cytoplasm. Like miniature sewage treatment plants, peroxisomes neutralise harmful toxins so that they do not wreak havoc in the cells. The liver is the organ primarily responsible for detoxifying the blood before it travels throughout the body, and liver cells contain an exceptionally high number of peroxisomes.
Defence mechanisms such as detoxification within the peroxisome and certain cellular antioxidants serve to neutralise many of these molecules. Some vitamins and other substances, found primarily in fruits and vegetables, have antioxidant properties. Antioxidants work by being oxidised themselves, halting the destructive reaction cascades initiated by the free radicals. Sometimes though, ROS accumulate beyond the capacity of such defences.
Free radicals are thought to play a role in many destructive processes in the body, from cancer to coronary artery disease.
Case study
Our patient, a 7-year-old female Labrador Retriever called Bella presents with symptoms of lethargy, decreased appetite, weight loss, occasional vomiting, dull coat, and skin lesions. Clinical examination shows pale mucous membranes, slightly elevated heart rate, elevated liver enzymes, and mild anaemia. Diagnostic testing can involve blood tests to detect elevated oxidative stress biomarkers, antioxidant levels, and urine analysis and ultrasound imaging to check for organ damage.
The diagnosis for Bella is oxidative stress, which is the term used to describe damage to cellular components caused by ROS. Due to their characteristic unpaired electrons, ROS can set off chain reactions where they remove electrons from other molecules, which then become oxidised and reactive, and do the same to other molecules, causing a chain reaction. ROS can cause permanent damage to cellular lipids, proteins, carbohydrates, and nucleic acids. Damaged DNA can lead to genetic mutations and even cancer. A mutation is a change in the nucleotide sequence in a gene within a cell’s DNA, potentially altering the protein coded by that gene. Other diseases believed to be triggered or exacerbated by ROS include cardiovascular diseases, diabetes, arthritis, and Huntington’s disease, among many others. It is noteworthy that these diseases are largely age-related. Many scientists believe that oxidative stress is a major contributor to the ageing process.
Treatment can include antioxidant supplementation Vitamin E, Vitamin C, Selenium, and dietary modifications to include antioxidant-rich foods (blueberries, spinach, carrots), high-quality protein.
