Transaminación y desaminación oxidativa

Metabolism of Nitrogen Compounds: Transamination and Deamination

Introduction to Transamination

• The first process in amino acid catabolism is transamination, primarily producing glutamate. This reaction involves the enzyme transaminase (or aminotransferase), which is crucial for the process.

• Transaminases are reversible enzymes that facilitate double displacement reactions between an amino acid and an alpha-keto acid, yielding a new amino acid and a new alpha-keto acid.

Mechanism of Transamination

• An example using alanine as the amino acid shows its structure with an amine group. The corresponding alpha-keto acid, represented as alpha-ketoglutarate, participates in this reaction.

• For transaminases to function effectively, they require a coenzyme known as pyridoxal phosphate (derived from vitamin B6). This coenzyme binds to the amino acid during the reaction.

• The mechanism involves first metabolizing the amino acid before transferring its nitrogen group to form a new compound. This results in pyruvate formation when alanine loses its amine group.

Formation of Glutamate

• After losing its amine group, alanine converts into pyruvate. The nitrogen compound then combines with another keto-acid to regenerate glutamate through transamination.

• The regenerated glutamate can then proceed to further metabolic pathways, including oxidative deamination.

Introduction to Deamination

• Following transamination, oxidative deamination occurs next in amino acid catabolism. Notably, three specific amino acids—serine, threonine, and proline—can undergo direct deamination without prior transamination.

• Glutamate serves as the primary substrate for oxidative deamination; it enters this pathway after being formed from previous reactions.

Mechanism of Oxidative Deamination

• Oxidative deamination takes place within mitochondria where glutamate reacts with water and is catalyzed by glutamate dehydrogenase (abbreviated as GDH).

Metabolism of Amino Acids and Urea Cycle

Formation of Nitrogenous Compounds

• The process begins with the removal of a nitrogen group from an amino acid, leading to the formation of a keto acid.

• This reaction allows for the integration back into the Krebs cycle, emphasizing its importance in energy metabolism.

Importance of Ammonium Ion (NH4)

• Humans lack protein storage; thus, excess amino acids must be degraded to prevent neurotoxicity from ammonium ions.

• Glutamate dehydrogenase plays a crucial role in this process and is regulated by ATP and GTP concentrations.

Integration into Urea Cycle

• NH4 produced enters the urea cycle, which occurs primarily in the liver, highlighting its significance in detoxifying ammonia.

Non-Oxidative Deamination Pathways

• Specific amino acids like serine undergo non-oxidative deamination rather than oxidative processes.

• The enzyme serine dehydratase converts serine into pyruvate while releasing NH4.

Key Metabolic Connections

• Pyruvate can enter gluconeogenesis, while α-ketoglutarate can transform into propionyl-CoA, linking amino acid metabolism to fatty acid oxidation.