Amino Acid Metabolism 2

Question 1

Transmination/Deamination

Answer 1

• The first step in AA catabolism is transamination followed by deamination
• Alternatively, instead of prodecing free NH₄⁺ through deamination, there can be double transamination, which prodces aspartate
• Both NH₄⁺ and aspartate re important in urea cycle

Question 2

Ammonia

Answer 2

• Ammonia (NH₃) is a strong base and is highly toxic
• In awueous soluction, it becomes NH₄⁺ and OH^-, increasing the pH
• Also, H₄⁺ (1.33A) intergeres with the brain’s ability to regulate K+ (1.43A)
• Amonia needs to be carefully regulated and disposed of as hazardous waste by the body

Question 3

Urea Cycle Overview

Answer 3

• A method for disposing of nitrogenous waste: 2 ammonia and 1 bicarbonate produces 1 urea
• Urea cycle occurs in the liver
• Inputs:
  
  • 2NH₄⁺, (from gulatmate)
  • HCO₃^-
  • 3ATP
  • Oxaloacetate (OR NAD⁺ in TCA cycle)
• Outputs:
  
  • Urea
  • 2ADP
  • AMP
  • 4P_i
  • Fumarate (OR NADH in TCA cycle)
• When TCA cycle is running, energy balance of urea cycle is slighly positve

Question 4

Step 1: Carbamoyl Phophate Synthetase

Answer 4

• Rate limiting step for urea cycle
• Committed step for Urea Cycle / Creatine synthesis
• Control Point:
  
  • N-acetylglutamate - an allosteric activator of CPS
  • N-acetylgutamate - produced when glutamate is high
• Occurs in mitochondria
• HCO₃^- + NH₄⁺ + 2ATP –> 2ADP + P_i + Carbamoyl Phosphate

Question 5

Regulation: N-acetylglutamate Synthetase

Answer 5

• Primary product AA catabolism is glutamate synthesized from a-ketogluterate during transamination
• High AA catablism leads to high glutamate concentrations
• N-acetylglutamate synthetase is activated by high glutamate concetrations, producing N-acetylglutamate
• N-acetylgulatmate acts as an allosteric activator for carbamoyl phosphate synthetase
• This balance urea production with nitrogen waste production in AA catabolism

Question 6

Step 2: Ornithine Transcarbamylase

and

Step 3: Arginosuccinate Synthetase

Answer 6

• Step 2: Ornithine Transcarbamylase
  
  • Occurs in mitochondria
  • Ornithine is tranported ot mitchondria and citrulline is transported to cytoplasm by ciitruline/ornithine antiporter
• Step3: Arginocuccinate Synthetase
  
  • Occurs cytoplasm

Question 7

Step 4: Arginocuccinate Lyase

and
Step 5a: Arginase

Answer 7

• Step 4: Arginosuccinate Lyase
  
  • OCcurs in cytoplasm
• Step 5a: Arginase
  
  • Occurs in cytoplasm
  • Restores ornithine
  • Urea is soluble waste

Question 8

Creatine Synthesis

Answer 8

Question 9

Step 5b: L-arginine: glycine Amidinotransferase

and

Step 6: Guanidinoacetate Methyltransferase

Answer 9

• Step 5b: L-arginine: glycine Amidinotransferase
  
  • Restores ornithine similar to arginase
• Step 6: Guanidinoacetate Methyltransferase

Question 10

Step 7: Creatine Kinase

Answer 10

• The creatine phosphocreatine reaction is used by muscle to store high energy phophate bonds
• During rest, high levels ATP are used to drive the reaction forward, producing phosphocreatine (acts as an ATP buffer)
• During high intensity work, phosphocreatine donates a phosphate to ADP to create ATP
• Creatine kinase spontaneously forms creatinine as a by product - used to assay renal function

Question 11

Forms of Nitrogen Waste

Answer 11

• Urea :
  
  • Primary nitrogen waste of ureotelic animals (mammals, amphibians)
  • Less toxic, more concentrated
  • Moderate water availablity
• Uric Acid :
  
  • Primary nitrogen waste of uricotelic animals (birds, terrestrial mammals, insects)
  • Even less toxic and more highly concentrated
  • Low water availability
• Ammonium :
  
  • Primary nitrogen waste of aquatic animals
  • Toxic
  • Only waste product by species that can freely dispose of it

Question 12

Uric Acid Synthesis Overview (Avian/ Reptile)

Answer 12