Catabolism of Amino Acids

Amino acids (AAs) can be acquired through the breakdown of intracellular or ingested dietary proteins. Amino acids can enter 3 metabolic routes within the body. They can 1) be recycled to synthesize new proteins; 2) combine with cofactors and substances to create amino acid derivatives; or 3) be catabolized into their functional groups and carbon skeletons. This process releases ammonium, which moves into the urea cycle and produces intermediates for energetic metabolic pathways.

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Amino acids (AAs) follow 3 main metabolic pathways for their metabolism:

  1. Synthesis of new proteins
  2. Formation of amino acid derivatives
  3. Catabolism of AAs
    • Catabolism consists of the breakdown of complex molecules into smaller units to produce energy or to be used in anabolic reactions
    • Removal or exchange of functional groups
      • Involves transamination, deamination, and decarboxylation
      • Releases excess nitrogen in the form of ammonium (NH4+), which then enters the urea cycle, is converted into urea, and excreted through the urine
    • Catabolism of the remaining carbon skeleton
      • In general, all 20 AAs can be broken down into 1 of 6 intermediates: pyruvate, acetyl-CoA, oxaloacetate, alpha-ketoglutarate, succinyl-CoA, and fumarate.
      • Ketogenic AAs metabolize to acetyl-CoA, later used in the citric acid cycle, ketogenesis, or fatty acid synthesis.
      • Glucogenic AAs are converted into glucose through gluconeogenesis.
      • Some AAs are both glucogenic and ketogenic.
Amino acid catabolism diagram

Schematic diagram of the metabolism of amino acids, including the 3 major pathways: reutilization in the synthesis of new proteins, union with cofactors to produce amino acid derivatives, and catabolism. Catabolism of amino acids includes the removal of functional groups and the breakdown of the carbon skeletons.

Amino Acid Derivatives

Amino acids can be used to assemble many substances. The image below shows the most important AA-derived substances in humans.

Amino acid derivatives

Amino acid derivatives. Amino acids (in blue) are combined with certain cofactors or other substrates (in pink) to make several biologically-important substances (in green).

Image by Lecturio.


Transamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2).

  • The original AA loses an amino group and gains a keto group, becoming an alpha-keto acid.
  • The original alpha-keto acid loses its keto group and gains an amino, becoming a nonessential AA.
  • The reaction is catalyzed by aminotransferase enzymes.
    • Can be specific for a particular AA pair or a group with similar chemical compositions
    • Requires coenzyme pyridoxal phosphate (PLP, the active form of vitamin B6)
    • Found in high concentrations in the liver

This process is need-dependent. If there is an excess of a type of AA, the amino group of that type can be transferred to make other types of AAs that the body currently needs.

All of the common AAs participate in transamination, except lysine, threonine, proline, and hydroxyproline, which catabolize via a dehydrogenase.

Transamination of aspartate and glutamate

Schematic diagram of the transamination reactions of aspartate and glutamate (glutamic acid). Amino groups are highlighted in red, while keto groups are highlighted in green.

Image by Lecturio.


  • Alanine transaminase (ALT or ALAT) transfers an amino group from alanine to alpha-ketoglutarate, forming pyruvate and glutamate. 
  • Aspartate transaminase (AST or ASAT) transfers an amino group from aspartate to alpha-ketoglutarate, forming oxaloacetate and glutamate.  

Both enzymes catabolize reversible reactions, which are essential for the transport of nitrogen from tissues to the liver and into the urea cycle.

Ping Pong Bi Bi mechanism of transamination

Ping pong bi-bi mechanism of PLP-dependent enzyme-catalyzed transamination. Aminotransferase reaction occurs in 2 stages consisting of 3 steps: transamination, tautomerization, and hydrolysis. In the first stage, the alpha-amino group of the amino acid is transferred to PLP, yielding an alpha ketoacid and pyridoxamine phosphate (PMP). In the second stage of the reaction, the amino group of PMP is transferred to a different alpha-keto acid to yield a new alpha-amino acid and PLP.

Image by Lecturio.


  1. PLP reacts with the amino group of the AA, releasing H2O.
  2. A Schiff base is formed, destabilizing the AA.
  3. Hydrogen atoms migrate, double-bond shifts, and aldimine → ketimine.
  4. H2O is added, yielding PMP and an alpha-keto acid.
  5. In reverse, PMP reacts with an alpha-keto acid, generating an AA and reconstituting PLP.


Deamination is the process through which amino groups are stripped from AAs, releasing free cytotoxic ammonia: ammonia → ammonium → urea or uric acid via the urea cycle in the liver.

Three types of deamination

1. Oxidative deamination

  • Oxidation turns the amino group into an imino group.
  • NAD+ or NADP+ is reduced to NADH/H or NADPH/H, respectively.
  • Water is added to the amino group, converting it to an alpha-keto group, releasing ammonia.
Oxidative deamination

Schematic diagram of the oxidative deamination reaction of glutamate. The nitrogen-containing functional groups are highlighted in red.

Image by Lecturio.

2. Hydrolytic deamination

Water reacts with the amino group, irreversibly attaching an OH group and eliminating the amino group in the form of ammonia.

Hydrolytic deamination reaction image

Schematic diagram of a hydrolytic deamination reaction. The nitrogen-containing functional groups are highlighted in red.

Image by Lecturio.

3. Eliminative deamination: 

  • Small AAs (serine or cysteine) release water (or hydrogen sulfide for sulfurous amino acids).
    • PLP is a necessary coenzyme.
  • Through hydrolysis, the amino group is cleaved, resulting in pyruvate.
Eliminative deamination

Schematic diagram of the eliminative deamination reaction of serine. The nitrogen-containing functional groups are highlighted in red, while the water molecule (H2O) and its components are highlighted in green.

Image by Lecturio.


  • Cleavage of a carboxyl group from an AA, releasing CO2
  • Catalyzed by the enzyme decarboxylase 
  • Uses PLP as a coenzyme
  • Resulting amines fulfill important functions in the body = biogenic amines
    • Histamine is formed through decarboxylation from histidine, and plays a vital role in immediate hypersensitivity reactions. 
    • Other examples: gamma-aminobutyric acid from glutamine acid and dopamine (from 3,4-dihydroxyphenylalanine).

Schematic diagram of the decarboxylation reaction of histidine to histamine

Image by Lecturio.

Catabolism of the Carbon Skeleton

The catabolism of AAs involves anaplerotic reactions (chemical reactions that form intermediates of metabolic pathways).

The breakdown of the carbon skeleton of AAs can be classified by the metabolic pathways to which their catabolic products will serve as intermediates. 

  • Glucogenic AAs → gluconeogenesis intermediates
  • Ketogenic AAs → ketogenesis intermediates
  • Glucogenic and ketogenic AAs → both pathways
Glucogenic AAsKetogenic AAsGlucogenic/Ketogenic AAs
  • Alanine
  • Arginine
  • Asparagine
  • Aspartic acid
  • Cysteine
  • Glutamic acid
  • Glutamine
  • Glycine
  • Histidine
  • Methionine
  • Proline
  • Serine
  • Valine
  • Lysine
  • Leucine
  • Isoleucine
  • Phenylalanine
  • Threonine
  • Tryptophan
  • Tyrosine

All AAs are broken down into 1 of 6 intermediates (see green boxes in the images below): pyruvate, acetyl-CoA, oxaloacetate, alpha-ketoglutarate, succinyl-CoA, and fumarate.

Catabolism of Amino Acids Diagram

The 3 categories of catabolic products of amino acids: glucogenic (green), ketogenic (red), and both glucogenic and ketogenic (blue). The glucose-pyruvate pathway on the left represents glycolysis and gluconeogenesis. The cyclic pathway on the right represents the citric acid cycle. All amino acids are broken down into 1 of 6 intermediates (green boxes): pyruvate, acetyl-CoA, oxaloacetate, alpha-ketoglutarate, succinyl-CoA, and fumarate.

Glucogenic AAs

Metabolized to pyruvate or metabolites of the citric acid cycle (CAC):

  • Pyruvate (from serine, cysteine, glycine, alanine, and threonine)
    • Threonine first → glycine → serine → pyruvate
  • Succinyl-CoA (from methionine, isoleucine, valine, and threonine via propionyl-Coa and methylmalonyl-CoA
  • Propionyl-CoA (intermediate of succinyl-CoA pathway)
  • Oxaloacetate (from asparagine via aspartate)
  • α-Ketoglutarate (from glutamine, arginine, histidine, proline via glutamate)
  • Fumarate

Catabolic products either move into the CAC to produce energy or are used as substrates for gluconeogenesis.

Ketogenic AAs

Metabolized directly to acetyl-CoA, then enter 1 of 3 metabolic pathways:

  • Enter the CAC to produce ATP/energy
  • Ketogenesis (production of ketone bodies)
  • Synthesis of fatty acids or cholesterol

Glucogenic and Ketogenic AAs

Metabolized to intermediates of lipidic as well as glucogenic pathways:

  • Isoleucine → propionyl-CoA (→ methylmalonyl-CoA → succinyl-CoA) and acetyl-CoA
  • Phenylalanine → tyrosine → fumarate and acetyl-CoA
  • Threonine → propionyl-CoA and pyruvate as well as acetyl-CoA (via glycine + acetaldehyde)
  • Tryptophan → alanine and acetyl-CoA

Mnemonic Device

To recall the metabolic pathways of the carbon skeletons of amino acids, remember:

  • Glucogenic: “I Met His Valentine, she is so sweet.”
    • Methionine
    • Histidine
    • Valine
  • Ketogenic: “The onLy pureLy ketogenic amino acids.”
    • Leucine
    • Lysine

Clinical Relevance

The following conditions are disorders of amino acid metabolism. Depending on the country and the individual U.S. state, newborn infants may be routinely screened for these disorders (except for alkaptonuria).

  • Phenylketonuria: a defect of phenylalanine hydroxylase that results in the impairment of the conversion of phenylalanine to tyrosine and subsequent accumulation of phenylalanine. Presents as psychomotor delay and seizures
  • Maple syrup urine disease: a defect in dehydrogenase that results in the accumulation of branched-chain AAs. Presents as cognitive disability, sweet-smelling urine, and dystonia 
  • Homocystinuria: a defect in the enzyme cystathionine β-synthase, which leads to an accumulation of homocysteine. Presents as flushing, developmental delay, lens dislocation, vascular disease, and osteoporosis
  • Tyrosinemia: a deficiency of fumarylacetoacetate hydrolase, the last enzyme in the tyrosine catabolism. Presents as liver disease, deficient weight gain, peripheral nerve disease, and kidney defects
  • Alkaptonuria: a deficiency of homogentisic acid dioxygenase, which impairs the normal degradation of tyrosine to fumarate. Presents as a bluish-black discoloration of connective tissues, arthritis, and calcifications of various tissues.

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