Dietary Protein: A primary source of amino acids for the amino acid pool.
Amino Acid Metabolism
Breakdown of the Amino Acid Pool
Components:
- Tissue Proteins: Contribute 4 to 8 mg/dL of amino acids.
Fates of Amino Acid Pool:
- Biosynthesis of Structural Proteins:
- Examples: Tissue proteins.
- Biosynthesis of Functional Proteins:
- Examples: Hemoglobin, myoglobin, protein hormones, and enzymes.
- Biosynthesis of Small Peptides of Biological Importance:
- Examples: Glutathione, endorphins, and enkephalins.
- Biosynthesis of Non-Protein Nitrogenous Compounds:
- Examples: Urea, uric acid, creatine, creatinine, and ammonia.
- Catabolism of Amino Acids:
- Results in ammonia and alpha-keto acids.
Catabolism of Amino Acids
Structure of an Amino Acid:
- Consists of an amino group and a carboxylic group.
Decarboxylation Reactions:
- The carboxylic group is removed as CO₂.
Transdeamination:
- Major process for removing the alpha-amino group in the form of ammonia.
Deamination:
- Can be oxidative or non-oxidative; a minor process in amino acid metabolism.
Products:
- Ammonia is detoxified to urea and excreted in urine.
- The remaining carbon skeleton can be converted to intermediates of energy-producing pathways (e.g., glycolysis and citric acid cycle).
- Can be metabolized to carbon dioxide, water, glucose (glucogenic), fatty acids, or ketone bodies (ketogenic).
Decarboxylation
Process:
- Amino acids undergo alpha decarboxylation to form corresponding amines.
- Catalyzed by the enzyme decarboxylase:
- ext{COOH}
ightarrow ext{CH}_3 ext{NH}_2 + ext{CO}_2.
Important Biogenic Amines Produced from Amino Acids:
- Histidine: Converted to histamine; acts as a vasodilator.
- Tyrosine:
- Converted to tyramine; acts as a vasoconstrictor.
- Tryptophan: Converted to tryptamine; functions as a neurotransmitter.
- Glutamic Acid: Converted to GABA; functions as a neurotransmitter.
Transamination
Definition:
- The transfer of an amino group from one amino acid to a keto acid, resulting in a new amino acid and a keto acid without releasing ammonia. Takes place in the liver.
Characteristics:
- Reversible process catalyzed by enzymes called transaminases (also known as amino transferases).
- Pyridoxal phosphate (PLP) serves as the coenzyme for transaminases.
Mechanism of Transamination:
Substrate amino acid (amino donor) is converted with the keto acid (amino acceptor).
Requires Pyridoxal Phosphate (PLP), derived from vitamin B6.
Involves degradation of amino acids, where the amino group is transformed into corresponding alpha-keto acids, entering catabolic pathways.
No free ammonia (NH3) is liberated; the process is simply an amino group transfer.
Catalyzed by transaminases; the reaction is reversible.
Amino groups of amino acids concentrate as glutamate, which is transported to the liver leading to release of ammonia via glutamate dehydrogenase.
Important for synthesis of non-essential amino acids from keto acids (e.g., pyruvate into alanine, alpha-ketoglutarate into glutamate).
Plays a role in gluconeogenesis; glucogenic amino acids like aspartate and alanine can convert to glucose via transamination.
Provides energy through compounds like oxaloacetate, pyruvate, and alpha-ketoglutarate entering glycolysis or TCA cycle.
Every amino acid except threonine, lysine, proline, and hydroxyproline undergoes transamination.
Not limited to alpha-amino groups; for example, the beta-amino group of ornithine can also be transaminated.
Serum transaminases have diagnostic and prognostic significance, such as AST and ALT.
Clinical Significance of Transaminases
Alanine Aminotransferase (ALT or SGPT):
- Elevated levels in serum indicate liver diseases like infective hepatitis due to liver damage.
- Normal serum level is 10-35 U/L.
Aspartate Aminotransferase (AST or SGOT):
- Elevated levels in serum signal myocardial infarction due to cardiac muscle damage.
- Normal serum level is 8-20 U/L.
Transamination allows for the synthesis of non-essential amino acids.
Deamination of Amino Acids
Definition: Deamination is the direct removal of an amino group from amino acids, releasing ammonia (NH₄).
Catalyzed by:
- L-amino Acid Oxidases:
- Act on all amino acids except hydroxy amino acids and dicarboxylic amino acids to produce alpha-keto acids and ammonia. Uses FMN as a co-enzyme.
- D-amino Acid Oxidases:
- Act on glycine and any D-amino acids found in plants and microorganisms, producing alpha-keto acids and ammonia. Uses FAD as a co-enzyme.
- Glutamate Dehydrogenase (GDH):
- Known for oxidative deamination; primarily associated with transdeamination reactions. Uses NAD or NADP+ as coenzymes.
Transdeamination
Concept: The amino group from amino acids is released via a coupled reaction called transdeamination, where transamination is followed by oxidative deamination of glutamate.
Process:
- Occurs in the cytoplasm where different amino acids transfer their amino group to alpha-ketoglutarate to form glutamate.
- Glutamate is then transported to the liver, oxidatively deaminated to alpha-ketoglutarate and ammonia in the mitochondria of hepatocytes.
- Free ammonia is highly toxic.
Steps of Transdeamination:
Transamination to form glutamate in all tissues.
Transport glutamate to liver.
Glutamate undergoes oxidative deamination by glutamate dehydrogenase.
Acts on specific amino acids:
- Serine: Converted to pyruvate and ammonia.
- Threonine: Converted to alpha-ketobutyrate and ammonia.
- Cysteine: Deaminated to pyruvate, ammonia, and hydrogen sulfide.
- Histidine: Deaminated to urocanate and ammonia.
Enzymes Involved in Non-Oxidative Deamination:
Serine Dehydratase:
- Converts serine to pyruvate and ammonia (PLP required).
Threonine Dehydratase:
- Converts threonine to alpha-ketobutyrate and ammonia (PLP required).
Desulphydratase:
- Converts cysteine to pyruvate, ammonia, and H₂S (PLP required).
Histidase:
- Converts histidine to urocanate and ammonia (PLP required).