U01.01.104 Transport of ammonia by alanine

Ammonia is a byproduct of amino acid metabolism, which can be toxic if accumulated. The body employs mechanisms such as the Cori Cycle, Cahill Cycle, and specific transport systems to efficiently handle ammonia, ensure energy production, and maintain nitrogen balance. Understanding these pathways is critical for USMLE Step 1 preparation.

Transport of Ammonia by Alanine

Ammonia produced in the muscle during amino acid metabolism is transported to the liver safely by being incorporated into alanine.

Key Steps:

Muscle:
- Amino acids undergo transamination, transferring the amino group to form glutamate.
- Glutamate reacts with pyruvate (produced from glycolysis) to form alanine via alanine transaminase (ALT).
Blood Transport:
- Alanine, containing the ammonia group, is transported through the bloodstream to the liver.
Liver:
- Alanine is transaminated back to pyruvate, releasing ammonia to form glutamate.
- Ammonia enters the urea cycle to form urea, which is excreted in urine.

Cori Cycle

The Cori Cycle facilitates lactate recycling between muscle and liver during anaerobic conditions.

Key Steps:

Muscle:
- Glucose undergoes glycolysis, producing ATP and lactate as a byproduct.
Blood:
- Lactate is transported to the liver.
Liver:
- Lactate is converted back to glucose via gluconeogenesis.
Recycling:
- Glucose re-enters the bloodstream, supplying energy back to the muscle.

Cahill Cycle (Glucose-Alanine Cycle)

The Cahill Cycle complements ammonia detoxification and gluconeogenesis.

Key Steps:

Muscle:
- Pyruvate combines with ammonia to form alanine.
Blood:
- Alanine travels to the liver.
Liver:
- Alanine is converted back to pyruvate, releasing ammonia.
- Ammonia enters the urea cycle, and pyruvate is used to generate glucose.

Metabolic Intermediates

The following intermediates are critical in these cycles:

Intermediate	Source	Function
Amino Acids (NH₃)	Protein breakdown	Provide nitrogen for alanine synthesis.
Pyruvate	Glycolysis	Combines with NH₃ to form alanine.
Alanine	Muscle to liver	Carries NH₃ safely in the blood.
Lactate	Anaerobic glycolysis	Transported to liver for gluconeogenesis.
Glutamate	Transamination	Transfers NH₃ during amino acid metabolism.
α-Ketoglutarate	TCA Cycle	Precursor for glutamate formation.

Points to Remember

Transport of Ammonia: Alanine and glutamine are key ammonia carriers.
Cori Cycle: Handles lactate to prevent acidosis during exercise.
Cahill Cycle: Transports ammonia and supports gluconeogenesis.
Liver: Central hub for ammonia detoxification via the urea cycle.
Clinical Correlation: Disruption in these cycles leads to hyperammonemia and metabolic disorders like lactic acidosis.

USMLE Step 1 Tips

Memorize the enzymatic steps in each cycle.
Focus on the interplay between muscle and liver metabolism.
Understand the relationship between intermediates and their physiological roles.

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USMLE Step 1 Review Series

Curriculum

U01.01.104 Transport of ammonia by alanine

Transport of Ammonia by Alanine

Key Steps:

Cori Cycle

Key Steps:

Cahill Cycle (Glucose-Alanine Cycle)

Key Steps:

Metabolic Intermediates

Points to Remember

USMLE Step 1 Tips

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