Amino Acids Metabolism_2024

Nitrogen Balance and Amino Acid Pool

  • Nitrogen balance measures nitrogen input (dietary protein) versus output (urea):

    • Positive balance: Protein synthesis > degradation (growth, recovery).

    • Negative balance: Protein synthesis < degradation (stress, malnutrition).

    • Equilibrium: Protein synthesis = degradation.

  • Amino Acid Pool:

    • Continuous exchange of free amino acids in tissues for protein synthesis, energy, and biosynthesis of nitrogen-containing compounds.

2. Overview of Amino Acid Metabolism

  • Amino acids serve as a source of nitrogen and carbon skeletons.

  • Amino acids undergo:

    • Degradation: Removal of the α-amino group.

    • Conversion into glucogenic or ketogenic intermediates for energy production.

3. Biosynthesis of Non-Essential Amino Acids

  • Synthesized through:

    1. Transamination: Transfer of amino groups to form new amino acids.

    2. Oxidative Deamination: Removal of amino groups as free ammonia.

    3. Modification of Carbon Skeletons: Using precursors like pyruvate or intermediates of glycolysis and the Krebs cycle.

4. Removal of Nitrogen from Amino Acids

  • Essential for energy production.

  • Occurs through two processes:

    1. Transamination:

      • Catalyzed by aminotransferases (ALT and AST), requiring pyridoxal phosphate (Vitamin B6).

      • Example: Alanine to pyruvate or glutamate to α-ketoglutarate.

    2. Oxidative Deamination:

      • Catalyzed by glutamate dehydrogenase, releasing ammonia.

      • NAD+ is used for oxidation, while NADPH is used for reductive amination.

5. Fate of the Carbon Skeletons

  1. Glucogenic Amino Acids:

    • Converted into glucose precursors (pyruvate, oxaloacetate).

    • Example: Alanine → pyruvate → glucose.

  2. Ketogenic Amino Acids:

    • Converted into ketone bodies via acetyl-CoA or acetoacetyl-CoA.

    • Example: Leucine.

  3. Glucogenic and Ketogenic Amino Acids:

    • Examples: Phenylalanine and Tyrosine.

6. Transport and Metabolism of Ammonia

  • Ammonia is toxic and transported to the liver for urea synthesis:

    • Tissues: Ammonia combines with glutamate to form glutamine (via glutamine synthetase).

    • Muscles: Ammonia forms alanine (via alanine transamination).

7. Urea Cycle

  • A major pathway for ammonia detoxification in the liver.

  • Enzymes involved:

    1. Carbamoyl Phosphate Synthetase: Forms carbamoyl phosphate.

    2. Ornithine Transcarbamylase: Converts carbamoyl phosphate and ornithine to citrulline.

    3. Argininosuccinate Synthetase: Forms argininosuccinate.

    4. Argininosuccinase: Cleaves argininosuccinate into arginine and fumarate.

    5. Arginase: Hydrolyzes arginine to form urea and ornithine.

8. Clinical Relevance

  • Hyperammonemia: Elevated ammonia levels, leading to CNS toxicity.

    • Causes: Liver failure, urea cycle enzyme deficiencies.

  • Markers for Liver Damage:

    • Elevated ALT and AST indicate liver or muscle damage.