Urea Cycle

Question 1

describe the synthesis of glutamine and alanine

Answer 1

• glutamine is formed in most tissues:
  
  • synthesized from glutamate
  • enzyme: glutamine synthetase
• alanine: synthesized in muscle
  
  • transamination from pyruvate
  • enzyme: ALT

Question 2

name the reactions of the urea cycle

Answer 2

1. CPS I: carbamoyl phosphate synthetase I
   
   • mitochondrial
   • activated by NAG
   • incorporates free ammonia
2. OTC: ornithine transcarbamoylase
3. ASS: argininosuccinate synthetase
4. ASL: argininosuccinate lyase
5. ARG: arginase

Question 3

all urea cycle disorders are characterized by increased blood ______ levels and elevated blood _____ levels

Answer 3

all urea cycle disorders are characterized by increased blood ammonia levels and elevated blood glutamine levels

Question 4

describe hyperammonemia type I

Answer 4

• enzyme deficiency: CPS I
• results in hyperammonemia
• sometimes responds to arginine intervention since Arg stimulates the formation of NAG; high levels of NAG might stimulate deficient CPS-I

Question 5

describe hyperammonemia type II

Answer 5

• enzyme deficiency: mitochondrial OTC
  
  • normally, OTC combines ornithine and carbamoyl phosphate to form citrulline
    
    • citrulline is transported to the cytoplasm where it combines with aspartate to form arginosuccinate
  • X-linked
  • most common
• results in hyperammonemia, increased orotic acid that is excreted in urine

Question 6

describe citrullinemia

Answer 6

• enzyme deficiency: arginonosuccinate synthetase
• results in hyperammonemia, increased citrullin levels

Question 7

describe argininosuccinic aciduria

Answer 7

• enzyme deficiency: ASL
• results in hyperammonemia, increased argininosuccinate levels

Question 8

describe argininemia

Answer 8

• enzyme deficiency: arginase
• results in increased arginine levels

Question 9

describe the urea cycle

Answer 9

Question 10

what are the only 3 enzymes that can fix free ammonia?

Answer 10

1. glutamate dehydrogenase
2. glutamine synthetase
3. CPS-I

Question 11

what is the management of hyperammonemia?

Answer 11

• administration of benzoic acid and/or phenylbutyrate/phenylacetate
  
  • benzoic acid eventually forms hippuric acid by combining with glycine
  • excreted in urine
• low protein/high carbs
  
  • minimize N intake