Urea cycle

Question 1

Glutamate Dehydrogenase (GDH)

Answer 1

• Incorporate NH4+ on alpha-KG producing glutamate

Question 2

Glutamine synthetase

Answer 2

• incorporate 2nd NH4+ ion to produce glutamine

Question 3

Transaminase Rxn

Answer 3

• transfers amino gr from aa to alpha-KG
• specific aminotransferases
• require PLP
• additionally: transfer from glu to pyr to produce alanine
• glutamate plays a central role in ammonia transport from tissues to the liver

Question 4

Formation of ammonia in liver

Answer 4

• Glu plays essential role in formation of NH3 for Urea Cycle:
  
  • Transamination
  • Oxidative deamination: GDH forms free ammonia
• Glu also produced from reverse rxn; removal of free NH3
• Ammonia also formed from glutamine by glutaminase rxn (free ammonia & glu are products)

Question 5

Intestinal formation of ammonia

Answer 5

• Bacterial ureases form ammonia in colon
• ammonia formed enters portal circulation; delivered back to liver
• intestinal formation of ammonia becomes significant in Pt with liver diseases

Question 6

Urea cycle overview

Answer 6

• converts toxic NH3 to non-toxic urea
• takes place in liver
• partly mitochondrial (2 rxn) & partly cytosolic (3 rxn)
• requires 2 nitrogen atoms:
  
  • one of N atoms of urea donated by ammonia (GDH & Glutaminase)
  • 2nd atom donated by Asp
• L-Asp also required for continuation of urea cycle
• obtained from degradation of proteins
• Fumarate released from urea cycle can be recycled
• NADH can be used to replenish ATP used in the cycle

Question 7

Regulation of Urea Cycle

Answer 7

• CPS-1 rate limiting step
• N-Acetyl Glutamate (NAG) is an allosteric & Obligate activator of the enzyme
• High protein diet, Arginine stimulates NAG
• Increased formation of NAG after a protein rich meal & in presence of arginine