6/24 UWorld

Question 1

Label the points on a Lineweaver-Burk plot (Y-intercept, X-intercept, and Slope)

Answer 1

Y-intercept = 1/Vmax

X-intercept = 1/-Km

Slope = Km/Vmax

Question 2

Describe the changes of a Michaelis-Mentin graph in the case of a competitive and noncompetitive inhibitor

(Changes in Km and Vmax)

Answer 2

• Competitive inhibitor (reversible)
  
  • Resembles substrate and competes for active site on enzyme
    
    • Can be overcome by increasing amount of substrate
  • Effects:
    
    • Increases Km – more substrate needed in order to achieve 1/2Vmax
    • Does not affect Vmax – can still reach Vmax with increased [S]
• Noncompetitive inhibitor (irreversible)
  
  • Binds to a separate site on the enzyme, causing a conformational change so the substrate can no longer bind
    
    • Cannot be overcome with increased substrate
  • Effects:
    
    • Decreases Vmax
    • Does not affect Km – changing substrate concentration will not help
      
      • Km increases by default because 1/2Vmax is a new number

Question 3

What drugs have zero-order elimination

Answer 3

Phenytoin, Ethanol, Aspirin

THINK: PEA – pea is round and shaped like a “0”

Question 5

Describe the kinin pathway

Answer 5

• Kallikrein cleaves plasminogen to plasmin
  
  • Plasmin breaks down the fibrin mesh
  • So factor XIIa is a regulator to make sure the coagulation cascade doesn’t go too crazy
• Kallikrein converts high molecular weight kininogen (HMWK) to bradykinin
  
  • Bradykinin has 3 functions:
    
    • Vasodilation
    • Increased vascular permeability
    • Pain mediator
  • This is why coagulation and inflammation are interconnected
• ACE is responsible for degrading bradykinin
  
  • So bradykinin can cause angioedema in patients taking ACEI

Question 6

MOA of fibrinolytics

Answer 6

Activate the conversion of plasminogen to plasmin

Question 7

Describe the defect and presentation of orotic aciduria

Answer 7

• Inability to convert orotic acid to UMP (de novo pyrimidine synthesis) due to defective UMP synthase
• Presentation:
  
  • Failure to thrive
  • Developmental delay
  • Megaloblastic anemia refractory to folate and B12
    
    • No hyperammonemia
      
      • Vs. Ornithine transcarbamylase deficiency which has increased orotic acid + hyperammonemia but no megaloblastic anemia
• Treatment:
  
  • Supplement dietary uridine (bypass the missing enzyme to provide substrate for UMP)

Question 8

What is a developmental field defect

Answer 8

Multiple malformations that occur secondary to an embryonic disturbance in an adjoining group of cells

Question 9

Where in the cell does the maturation of RNA (5’ cap, poly-A tail, intron splicing) occur?

Answer 9

Nucleus