52. Amino Acid Metabolism in Liver, Gut and Kidney.

Amino Acid Metabolism in Liver, Gut and Kidney

• General Concept
• Amino acids enter the body via diet and endogenous protein turnover.
• Since the body cannot store amino acids, they are constantly being used for:
• Protein synthesis
• Energy production
• Synthesis of specialized molecules
• Disposal of excess nitrogen

1) Liver: The Central Organ of Amino Acid Metabolism

• Liver is the main site for regulation of blood amino acid levels.
• It maintains a balance between intake, synthesis, breakdown, and conversion.
• Transamination reactions occur mainly in the liver.
• Transfer of amino groups between ketoacids to form new amino acids.
• Requires Vitamin B6 (pyridoxal phosphate).
• Urea Cycle Occurs Exclusively in the Liver
• Liver converts toxic ammonia to urea for safe excretion by kidneys.
• Failure of liver → ammonia accumulation → hepatic encephalopathy.
• Catabolism of Most Amino Acids Happens in Liver
• The carbon skeleton enters the TCA cycle, gluconeogenesis, or ketogenesis.
• Liver synthesizes non-essential amino acids
• For example: Alanine, Aspartate, Glutamate, Serine, Cysteine, etc.
• Liver produces plasma proteins (important for osmotic pressure and clotting)
• Albumin
• Fibrinogen
• Clotting factors
• Liver plays a role in transport of nitrogen between tissues
• Receives alanine from muscle during fasting (glucose-alanine cycle).
• Converts alanine → pyruvate → glucose → returned to muscle.

2) Gut (Intestine): First Site of Dietary Amino Acid Handling

• Intestinal mucosal cells absorb amino acids and small peptides
• Peptidases break dietary protein into absorbable units.
• Gut uses certain amino acids for its own energy
• Glutamine is the major fuel for intestinal cells (not glucose).
• Glutamine is converted to Glutamate and then to Alanine
• Alanine is released into the bloodstream and sent to liver.
• Enterocytes convert dietary glutamate into key metabolic molecules
• e.g., α-ketoglutarate (enters TCA cycle for energy production).
• Dietary Amino Acids Not Immediately Used Enter Portal Vein → Liver
• So the liver sees absorbed amino acids first before they enter systemic circulation.

3) Kidney: Key Role in Nitrogen Handling

• Kidneys excrete nitrogen waste primarily as urea, formed in liver.
• But Kidney plays a vital role in ammonia production and pH regulation
• In metabolic acidosis:
• Kidney increases glutaminase activity.
• Glutamine → Glutamate + Ammonia (NH3).
• NH3 binds H+ → forms NH4+, excreted in urine.
• Helps buffer blood pH.
• Kidneys also perform Gluconeogenesis in prolonged fasting
• Use glutamine as a substrate.
• Kidneys regenerate Serine from Glycine, helping maintain amino acid balance.
• Some Amino Acids are conserved and reabsorbed in proximal tubule
• If reabsorption fails (like in cystinuria) → amino acids appear in urine → kidney stones.