Amino Acid Deamination

• While amino acids can be recycled for new proteins, they can also be degraded, and this requires deamination of the amino groups!
• amino acid deamination occurs mainly in the liver, although also muscle
• three general steps of deamination:

  1. transaminase
  2. glutamate dehydrogenase
  3. urea cycle
• The transaminase reaction has reactants that involve an amino acid and an alpha-ketoglutarate (which is an alpha-ketoacid), and the products are also an amino acid (specifically glutamate) and an alpha-ketoacid
• Transaminase catalyzes a "ping-pong" mechanism, so called because one substrate binds at a time
• pyridoxal phosphate (PLP) = transaminase cofactor, derived from vitamin B6; creates a Schiff base with the amino acid and acts as an electron sink
• PLP attaches to transaminase as a cofactor through lysine
• transaminase ping pong:

  1. Ping = removing amino group from amino acid
  2. Pong = transferring amino group to alpha-ketoglutarate to form glutamate
• the second step of amino acid deamination, glutamate dehydrogenase, involves NAD+ to oxidize glutamate, and then uses water to remove ammonium and regenerate the alpha-ketoglutarate
• the Cahill cycle cycles glucose and alanine between the liver and muscle tissues, and is a way of using amino acids for fuel
• Cahill cycle:

  • muscles: amino acid deamination produces ammonium that can be combined with pyruvate from glycolysis to form alanine
  • liver: alanine is converted back to pyruvate and converted to glucose through gluconeogenesis
  • essentially alanine is used to transfer between muscles and liver