3 Amino acids metabolism

• Amino acid metabolism


  1. Transamination

  2. Deamination
• The amino acids undergo certain common reactions like transamination followed by deamination for the liberation of ammonia
• The amino group of the amino acids is utilized for the formation of urea which is an excretory end product of protein metabolism
• The carbon skeleton of the amino acids is first converted to keto acids (by transamination)
• Fates of keto acids

  • Utilized to generate energy
  • Used for the synthesis of glucose
  • Diverted for the formation of fat or ketone bodies
  • Involved in the production of non-essential amino acids
• Transamination


  The transfer of an amino (-NH2) group from an amino acid to a keto acid
• Transamination


  1. Transfer of amino group to coenzyme pyridoxal phosphate

  2. Transfer of amino group to a keto acid
• Salient features of transamination

  • All transaminases require pyridoxal phosphate (PLP)
  • Specific transaminases exist for each pair of amino and keto acids
  • Only two transaminases make a significant contribution for transamination
  • No free NH3 liberated, only the transfer of amino group occurs
  • Transamination is reversible
  • Important for redistribution of amino groups and production of non-essential amino acids
  • Involves both catabolism and anabolism of amino acids
  • Diverts excess amino acids towards energy generation
  • Concentrates nitrogen in glutamate
  • All amino acids except lysine, threonine, proline, and hydroxyproline participate in transamination
  • Not restricted to alpha-amino groups only
• Transamination is very important for the redistribution of amino groups and production of non-essential amino acids, as per the requirement of the cell
• Transamination diverts the excess amino acids towards energy generation
• The amino acids undergo transamination to finally concentrate nitrogen in glutamate
• Glutamate is the only amino acid that undergoes oxidative deamination to a significant extent to liberate free NH3 for urea synthesis
• Transamination is not restricted to alpha-amino groups only
• Mechanism of transamination


  1. Transfer of the amino group to the coenzyme pyridoxal phosphate

  2. Transfer of the amino group of pyridoxamine phosphate to a keto acid
• Deamination


  The removal of amino group from the amino acids as NH3
• Deamination results in the liberation of ammonia for urea synthesis
• Simultaneously, the carbon skeleton of amino acids is converted to keto acids
• Types of deamination


  • Oxidative deamination
  • Non-oxidative deamination
• Although transamination and deamination are separately discussed, they occur simultaneously, often involving glutamate as the central molecule
• Oxidative deamination


  The liberation of free ammonia from the amino group of amino acids coupled with oxidation
• This takes place mostly in liver and kidney
• The purpose of oxidative deamination is to provide NH3 for urea synthesis and alpha-keto acids for a variety of reactions, including energy generation
• Role of glutamate dehydrogenase


  Enzyme that catalyzes the oxidative deamination of glutamate
• Glutamate serves as a 'collection centre' for amino groups in the biological system
• Glutamate rapidly undergoes oxidative deamination, catalyzed by glutamate dehydrogenase (GDH) to liberate ammonia
• GDH is unique in that it can utilize either NAD+ or NADP+ as a coenzyme
• Conversion of glutamate to alpha-ketoglutarate occurs through the formation of an intermediate, alpha-iminoglutarate
• GDH-catalyzed reaction is important as it reversibly links up glutamate metabolism with TCA cycle through alpha-ketoglutarate
• GDH is involved in both catabolic and anabolic reactions
• Regulation of GDH activity

  GDH is a zinc-containing mitochondrial enzyme
• GDH is a complex enzyme consisting of six identical units with a molecular weight of 56,000 each
• GDH is controlled by allosteric regulation
• GTP and ATP inhibit whereas GDP and ADP activate glutamate dehydrogenase
• Steroid and thyroid hormones inhibit GDH
• After ingestion of a protein-rich meal, liver glutamate level is elevated
• It is converted to alpha-ketoglutarate with liberation of NH3
• When the cellular energy levels are low, the degradation of glutamate is increased to provide alpha-ketoglutarate which enters TCA cycle to liberate energy
• Oxidative deamination by amino acid oxidases

  1. Amino acid oxidase and D-amino acid oxidase are flavoproteins
• They act on the corresponding amino acids (L or D) to produce alpha-keto acids and NH3
• In this reaction, oxygen is reduced to H2O2, which is later decomposed by catalase