Read the summary and the most important questions on HAP-31806 Molecular regulations of health and disease

• Theme 1: Molecular regulation of energy and nutrient metabolism

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• What are the two types of phases in cancer cells and what is their metabolic geprogrammed for?

  Proliferation:
  Metabolic reprogramming to maximize:
  

  • Biomass
    
  • Energy (ATP)
    

  
  Survival:
  Metabolic reprogramming to maximize:
  

  • Alternative fuels
    
  • Anti-oxidant defense
    

• How does the Warburg effect benifit cancer?

  • Rapid ATP synthesis: glycolysis to pyruvate is faster then al the way through the mitochondria.
    
  • Biosynthesis: glycolysis to pyruvate has multiple products that can be used for DNA and proteins. Reductive carboxylation allows biosynthesis during hypoxia. 
    
  • Tumor microenvironment: accidification promotes invasiveness. Taking away the glucose from native immune cells.
    
  • Cell signalling: allows for signalling transduction through ROS and/or chromatin modulation.
    

• Do cancer cells need mitochondria?

  Yes.
  Pyruvaat, (NADH-->NAD+), AKB, nucleotides and aspartate rescue tumor cells with OXPHOS deleted mitochondria. Aspartate biosynthesis is essential for mitochondrial defective cells. Oxidative phosphorylation in cancer cells is needed to oxidize NADH with oxygen.
  
  Mitochondria are needed for biosynthesis and oxidative phosphorylation.

• What are the four kind of cancer therapies?

  Radiotherapy
  Surgery
  Chemotherapy
  Immune therapy

• How would you block tumor growth via PKM2 and why?A) A drug that activates PKM2B) A drug that inhibits PKM2

  I would use a drug that activates PKM2:
  PKM1 has high constitutive activity, PKM2 has low activity and ensuring to activate the upstream Pentose Phosphate Pathway (PPP). When PKM2 is activated it becomes more like PKM1, therefore inhibiting PPP and activating PEP ---> pyruvate action. (activating its tetramer form)

• Theme 2: Microbiota in health and disease

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• Name a few things that are associated with GI tract microbiota in health and disease.

  Allergy, autism, clostridium difficile infection, chrohn's disease, eczema, inflammatory bowel syndrome, metabolic syndrome, nutrient processing, obesity, prebiotics, probiotics, synbiotics, type 1+2 diabetes, ulcerative colitis.

• What is the distibution of GI tract microbes?

  Stomach: <10^3 bacteria/gram, many facultative anaerobes
  
  Small intestine: 10^5-10^7 bacteria/gram, many facultative anaerobes 
  
  Colon: ?10^11 bacteria/gram, >99% strict anaerobes

• Why is the small intestinal ecosystem driven by rapid uptake and conversion of simple sugars of fast growing microbes, such as streptococcus?

  Because there is a fast transit of contents (3-10 hours) and the host absorbes a lot of the metabolites.

• Name some functions of GI tract bacteria.

  • Fermentation of indigestible carbohydrates
    
  • Development GI tract structure and immune system
    
  • Resistance against pathogens
    
  • Improved metabolite absorption
    
  • Production short chain fatty acids (SCFA)
    
  • Production of vitamins
    
  • Deconjugation bile acids
    

  
  many more....

• Why is the ecosystem in the large intestine driven by conversion of complex indigestible polysacharides?

  Because the transit time is slow (24-72 hours) therefore there is more time to ferment the products and the host metabolic absorbtion is lower. Upstream the simple sugars have been converted and absorbed by the host.