Read the summary and the most important questions on Molecular Regulations of Health and Disease

• Molecular regulation of energy and nutrient metabolism

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• What are the 5 differences between cancer cells and normal cells? 

  1. Cancer cells are immortal and can grow indefinitely. 
  
  2. Cancer cells diplay sufficiency in growth signals. They display lower growth signal requirements. In a tissue medium cancer cells require much less serum than normal cells. 
  
  3. Cancer cells are invasive and have properties that support invasion and metastasis. 
  
  4. Cancer cells are resistant to apoptosis.
  
  5. Cancer cells have an altered nutrient and energy metabolism.

• Name two examples how cancer cell nutrient and energy metabolism is altered. 

  1. Cancer cells show an increased rate of glycolysis. There is an increased uptake of glucose and a corresponding increase in lactic acid production in cells of solid tumours. Increased glucose uptake can be used to diagnose specific cancers with PET imaging. 
  
  2. Cancer cells have a more negative surface charge of the cell membrane and sustained angiogenesis. A more negative cell surface facilitates uptake of nutrients just like angiogenesis.

• 1.2: Mitochondria

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• What is the main function of mitochondria? And what is the main function of mitochondria in cancer cells?

  In normal cells; the production of ATP is the main function of mitochondria. 
  1. They produce ATP.
  2. They respond to cellular energy demand.
  3. They have a regulatory role in the balanced use of energy substrates. 
  4. ""  """"                                                                      in the urea cycle.
  5. ""                                                                             in calcium homeostasis.
  6. "" in amino acid metabolism. 
  7. They are essential for heme and iron-sulphur cluster biosynthesis.
  8. They mediate apoptosis.
  9. They mediate innate immune defence.
  10. Oxidative signalling are produced in the mitochondria and play a role in several of its functions. 

• Explain: Electron Transport Complexes.

  This repiratory chain consists of a series of enzyme systems coupled together and that are described as: Complex I (NADH dehydrogenase), II (succinate dehydrogenase), III (cytochrome c reductase), IV (cytochrome c oxidase) and V. 
  
  Electrons are transferred from NADH to complex I or from FADH (succinate) to complex II. 
  Then the electrons are transferred to ubisemiquinone which shuttles them to complex III. From Complex II aswell. 
  Cytochrome c shuttles them to complex IV.
  Here the electrons are transferred to oxygen to form H2O. The use of oxygen is called respiration. 

• Microbiota in health and disease lecture 1

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• Why is the small intestine a harsh environment for microbes? And the stomach?

  The small intestine is harsh because it has a fast transit time of food components - only a few hours max. Furthermore bile is present and digestive digestive enzymes.
  
  The stomach has a very acidic pH and also a very fast transit time (30 min). Only acidic microbes can survive this environment.

• Which 3 components are important for the regulation of health and disease in and interact in the GI-tract?

  1. Diet and Food
  2. GI-tract microbes
  3. Human host
  
  GI-tract microbes convert non-digested food components and produce certain vitamins, SCFA and are involved in immune modulation.
  
  The human host digests and takes up food components and produce antimicrobial peptides and endogenous substrate and are therefore important for the immune respons.

• Why is collecting microbes from the small intestine difficult?

  It is very invasive to achieve microbiota, it is very inaccessible. Most information comes from sudden death individuals or collected from ileostomy patients (no colon). Collection via catheter or surgery is possible, but very invasive.

• Why is the small intestine largely driven by rapid uptake and conversion of simple sugars?

  These sugars can be used by other members of this community such as Veillonella and butyrate producers. Microbiota in the small human intestine are therefore maintained.

• Why is the colon the fermentation 'vessel' of the human GI tract?

  Because it has a slow transit time and food components that have escaped digestion in the small intestine can be converted by microbes into components that can be absorbed.

• Explain the model of bacterial life in the small intestine.

  See lecture 2.1, slide 17