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Biochem

1. Case Study: More Than Just Tired
We all get tired sometimes, especially if we have been doing a lot of physical activity, like the hikers pictured here. But for Jasmin, a 34-year-old former high school track star who is now a recreational runner, her tiredness was going far beyond what she thought should be normal for someone in generally good physical shape. She was experiencing extreme fatigue after her runs, as well as muscle cramping, spasms, and an unusual sense of heaviness in her legs. At first, she just chalked it up to getting older, but her exhaustion and pain worsened to the point where the former athlete could no longer run for more than a few minutes at a time. She began to experience other unusual symptoms, such as blurry vision and vomiting for no apparent reason.
Concerned, Jasmin went to her doctor, who ran many tests and consulted with several specialists. After several months, she is finally diagnosed with a mitochondrial disease. Jasmin is surprised. She has an 8-year-old niece with a mitochondrial disease, but her nieces symptoms started when she was very young, and they included seizures and learning disabilities.

1. Jasmin discovered that her extreme fatigue, muscle pain, vision problems, and vomiting were due to problems in her mitochondria, like the damaged mitochondria shown in red in the picture above. Mitochondria are small, membrane-bound organelles found in eukaryotic cells that provide energy for the cells of the body. They do this by carrying out the final two steps of aerobic cellular respiration (the Krebs cycle and electron transport), which is the major way that the human body breaks down the sugar glucose from food into a form of energy cells can use, namely the molecule ATP.
Because mitochondria provide energy for cells, you can probably easily see why Jasmin was experiencing extreme fatigue, particularly after running. Her damaged mitochondria could not keep up with her need for energy, particularly after intense exercise, which requires a lot of additional energy. What is perhaps not so obvious are the reasons for her other symptoms, such as blurry vision, muscle spasms, and vomiting. All of the cells in the body require energy in order to function properly. Mitochondrial diseases can cause problems in mitochondria in any cell of the body, including muscle cells and cells of the nervous system, which includes the brain and nerves. The nervous system and muscles work together to control vision and digestive system functions, such as vomiting, so when they are not functioning properly, a variety of symptoms can emerge. This also explains why Jasmins niece, who has a similar mitochondrial disease, has symptoms related to brain function, such as seizures and learning disabilities. Our cells are microscopic, and mitochondria are even tinier but they are essential for the proper functioning of our bodies. When they are damaged, serious health effects can occur.
One seemingly confusing aspect of mitochondrial diseases is that the type of symptoms, severity of symptoms, and age of onset can vary wildly between people even within the same family! In Jasmins case, she did not notice symptoms until adulthood, while her niece had more severe symptoms starting at a much younger age. This makes sense, however, when you know more about how mitochondrial diseases work.
Inherited mitochondrial diseases can be due to damage in either the DNA in the nucleus of cells or in the DNA in the mitochondria themselves. Recall that mitochondria are thought to have evolved from prokaryotic organisms that were once free-living, but were then infected or engulfed by larger cells. One of the pieces of evidence that supports this endosymbiotic theory is that mitochondria have their own, separate DNA. When the mitochondrial DNA is damaged (or mutated) it can result in some types of mitochondrial diseases. However, these mutations do not typically affect all of the mitochondria in a cell. During cell division, organelles such as mitochondria are replicated and passed down to the new daughter cells. If some of the mitochondria are damaged, and others are not, the daughter cells can have different amounts of damaged mitochondria. This helps explain the wide range of symptoms in people with mitochondrial diseases even ones in the same family because different cells in their bodies are affected to different extents. Jasmins niece was affected strongly and her symptoms were noticed early, while Jasmins symptoms were more mild and did not become apparent until adulthood.
There is still much more that needs to be discovered about the different types of mitochondrial diseases. But by learning about cells, their organelles, how they obtain energy, and how they divide, you should now have a better understanding of the biology behind these diseases.
Apply your understanding of cells to your own life. Since your entire body is made of cells, when cells are damaged or not functioning properly, it can cause a wide variety of health problems.

1. How can Jasmin have the same disease, but different symptoms? Why didn’t she have problems until adulthood, while her niece experienced symptoms at an early age? And what are mitochondria, anyway?

2. Can you think of other diseases that affect cellular structures or functions? Do they affect people you know?

After you read the two passage above, answer these two questions. Question no. 1 goes with passage 1 and question no. 2 goes with passage 2.

 

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