Lecture 03

• What is the general composition of enzymes?

  Enzymes need a co-factor (holoenzyme)

  
• What are the types of co-factors needed by enzymes?

  Prosthetic groups, metal ions, coenzymes
• What is a prosthetic group?

  Covalently bonded group to the protein
• Give an example of a prosthetic group.

  Haem in haemoglobin
• What is the active site of an enzyme?

  A cleft or cavity where substrate binds

  
• How is the active site complementary to the substrate?

  In size, shape, charge, and hydrophobicity
• Why might active site residues be distant in sequence?

  They can be brought together in 3D structure
• What does the Lock and Key model explain?

  Specificity of enzymes with rigid active sites
• What is a limitation of the Lock and Key model?

  It cannot explain enzymes acting on many substrates
• What happens in the Induced Fit model?

  Substrate induces a change in enzyme structure
• How does hexokinase demonstrate the Induced Fit model?

  It phosphorylates glucose to glucose 6-phosphate
• What occurs in DNA helicase during substrate binding?

  One domain rotates when binding DNA
• What is an allosteric enzyme?

  An enzyme with an additional binding site

  
• What is the structure of PFK2?

  It has kinase and phosphatase domains

  
• What is a chiral carbon?

  A carbon atom with four different groups
• What does the 3-point attachment model explain?

  Substrate binds at three distinct points
• Why is the 3-point attachment model important?

  It ensures specific interactions with enantiomers
• What is the lifespan of normal red blood cells?

  ~120 days in the bloodstream
• What happens to sickle cells compared to normal cells?

  Sickle cells die after 10-20 days
• What is the consequence of sickle cells in the bloodstream?

  They cause blockages and oxygen deprivation
• What is the molecular mechanism behind sickle cell disease?

  Hydrophobic interactions cause HbS polymerisation
• What amino acids are encoded by GAG and GTG codons?

  Glycine and Valine
• What is the most common lipid storage disease?

  Gaucher disease
• What causes Gaucher disease?

  Mutations in acid-β-glucosidase enzyme
• What is the result of mutations in acid-β-glucosidase?

  Reduced catalytic activity of the enzyme
• What happens to the conformation of acid-β-glucosidase with mutations?

  It stabilises a closed conformation
• What is the consequence of the Glutamate to Valine mutation in hemoglobin?

  Causes aggregation into fibers
• What is the effect of mutations on protein structure?

  They may cause changes leading to disease

  
• What are the key points regarding enzyme structure and function?

  • Active site is where substrate binds
  • Lock and Key model: rigid active site
  • Induced Fit model: substrate induces structural change
  • 3-point attachment model: substrate forms three connections
• What are the key points regarding diseases related to protein structure?

  • Sickle cells live 10-20 days, causing anemia
  • Hydrophobic interactions lead to sickle shape
  • Gaucher disease caused by mutations in acid-β-glucosidase
  • Mutations reduce enzyme activity and cause accumulation of glucosylceramide