Metabolism — Ammonia & Lactulose

Formation of Urea from Ammonia

• Liberation of ammonia from AAs
• Formation of carbamoyl phosphate from NH3
• Reactions of the urea cycle

Urea Cycle

• Ammonia carried in blood from tissues to liver mitochondria by glutamate as amino groups.
• Hepatocyte Mitochondria
  • 2ATP+CO2+NH3 + Carbamoyl Phosphate → citrulline using enzyme Carbamoyl phosphate synthetase 1
• Hepatocyte Cytosol
  • Citrulline + ATP + H2O → ornathine + urea
• Urea Fate:
  • Enterohepatic circulation (25%)
  • Excreted by kidneys (75%).
• Ornathine reenters the mitochondria and is combined with new carbamoyl phosphate to form citrulline

Excretion of ammonia by Kidney

1. Ammoniagenesis:
   • Glutamine enters the  peritubular cells of the PCT
     • 80% from the peritubular capillaries
     • 20% from the filtrate, reabsorbed by PCT
   • Deaminated via Glutaminase (increased activity in acidosis)
   • HCO3 reabsorbed into peritubular capillary blood
   • NH4 excreted via Na/NH4 antiporter
2. Ammonium cycling:
   • 80% reabsorbed TAL of LoH via replacing K on Na/K/2Cl cotransporter
   • Increased conc in medullary intersitium
   • Diffuses down conc grad into CD
   • Buffer ability can be utilised to excrete H.

Pharmacology of Lactulose:

Gladwin 2016

Answer by Gladwin