Summary: Toxicologie

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• 2 Signal transduction

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• Difference between fast and slow signaling.

  Altered protein function vs altered protein synthesis.

• What are the elements of signal transduction?

  Sensor – receptor of signal
  Transducer – relay of signal, e.g. kinase
  Effector – e.g. transcription factor, protease

• Of what consists the MAPK pathway?

  Starts with activated RAS 
  - Dan Raf, Mek, Erk. (Kinases, p erbij)

• What are two stress kinase pathways?

  • P38
  • JNK - c-Jun

• Many compounds can inhibit kinase pathways. Where are they often used for?

  Anti-cancer.

• What is the relation between apap (paracetamol) and activation of JNk?

  • Only in case of overdosis.
  • In that case a metabolite is generated: NAPQI.
  • Normally neutralisation with Glutathion.
  • In high doses -> stress 
  • ROS -> MAKP pathway 
  • JNK will be activate 
  • More ROS production + mitochondrial stress    

• How does the Proteasomal protein degradation work?

  • Ub wordt geactiveerd 
    
  • UB wordt gekoppeld aan E2 om samen met het substraat aan E3 te gaan. 
  • UB keten wordt gemaakt door K48 linkages 
  • Proteasome herkent het 

• What is a possible role of ubiquitine in alzheimer disease?

  Difference between risk for male/female. 
  Acetylation => blocks ubiquitination.

• 3 Stress response pathways

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• What happens in general, when you are exposed to a molecule (drug)?

  Allostasis => adaption to function suboptimal.

• Describe how a transcription factor works, is activated or inhibited.

  • The TF is in the cytosol, bind to another molecule. 
    
  • The enzyme ubiquitin ligase can attract ubiquitine. 
  • This is a signal to be degradated. 
  • Phosphorylation can block the ligase, preventing degradation 
  • It goes to the nucleus, bind to a aux protein and bind to the DNA

  
  
  MULTIPLE consequences. 
  

  • Negative feedback => decrease its own production. 
  • Transcription of different genes.