8/20/23, 10:42 AM Catabolism of Amino Acids - Lecturio

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.

Last updated: February 17, 2023

CONTENTS

Overview
Amino Acid Derivatives
Transamination
Deamination
Decarboxylation
Catabolism of the Carbon Skeleton
Clinical Relevance

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

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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, or
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.

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8/20/23, 10:42 AM Catabolism of Amino Acids - Lecturio

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.

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8/20/23, 10:42 AM Catabolism of Amino Acids - Lecturio

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
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).
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8/20/23, 10:42 AM Catabolism of Amino Acids - Lecturio

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.

Schematic diagram of the transamination reactions of aspartate and glutamate (glutamic acid):
Amino groups are highlighted in red.
Keto groups are highlighted in green.
Image from Lecturio

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

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8/20/23, 10:42 AM Catabolism of Amino Acids - Lecturio

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 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.

Steps:
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
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8/20/23, 10:42 AM Catabolism of Amino Acids - Lecturio

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.

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.

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The nitrogen-containing Medical
functional groups
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are highlighted in red.

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8/20/23, 10:42 AM Catabolism of Amino Acids - 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.

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.

Decarboxylation
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
Dopamine from 3,4-dihydroxyphenylalanine

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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 AAs Ketogenic AAs Glucogenic/Ketogenic AAs

Alanine Lysine Isoleucine

Arginine Leucine Phenylalanine
Asparagine Threonine
Aspartic acid Tryptophan
Cysteine Tyrosine
Glutamic acid
Glutamine
Glycine
Histidine
Methionine
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Valine
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8/20/23, 10:42 AM Catabolism of Amino Acids - Lecturio

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, or
fumarate.

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, or fumarate.

Glucogenic AAs

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

Pyruvate (from serine, cysteine, glycine, alanine, and threonine)
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)
-Ketoglutarate
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Fumarate
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Catabolic products either move into the CAC to produce energy or are used as
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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
To recall the metabolic pathways of the carbon skeletons of amino acids, remember:
Glucogenic: “I MetHisValentine, 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).

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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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