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AMINO ACID METABOLISM

INTRODUCTION
Amino acids are the basic structural units (building blocks) of proteins
These biomolecules have four chemical groups or moieties around a central
carbon atom.
An α-amino acid consists of:
1. An amino group
2. A carboxyl (acidic) group
3. A hydrogen atom
4. A distinctive R group
5. A central α carbon atom

The R group is also called a side chain.

The tetrahedral array of four chemical groups about the α carbon atom confers optical
activity on amino acids- we have L and D optical isomers of the same amino acid.

But only L amino acids are constituents of proteins.

There are 20 different R groups, which vary in size shape, charge, chemical
reactivity and polarity.
All proteins in all species are constructed from the same set of 20 amino acids.

CLASSIFICATION OF AMINO ACIDS

1. Nonpolar, aliphatic R groups: - H, CH3
(glycine, valine, alanine, leucine, isoleucine, proline)
2. Aromatic, with cyclic groups:
(phenylalanine, tyrosine, tryptophan)
3. Polar uncharged R groups: –CH2OH, –CH2SH
(serine, threonine, cysteine, methionine, aspartate, glutamate)
4. Polar/ Basic positively charged R groups: –+NH3
(arginine, lysine histidine)
5. Polar/Acidic negatively charged R groups : –CH2COO-
(asparagine, glutamine)
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STRUCTURE of AMINO ACIDS (At PH 7)

(The R group is highlighted)
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NB
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ESSENTIAL AMINO ACIDS

All 20 amino acids found in proteins are synthesized by plants.

 Humans do not have all the enzymes required for biosynthesis of all amino acids.
The remaining must be obtained from the diet. These are called the essential
amino acids. (Indispensable)
 The essential amino acids are: arginine, histidine, isoleucine, leucine, lysine,
methionine, phenylalanine, threonine, tryptophan, and valine.
 Mammalian cells lack enzymes to synthesize their carbon skeletons.
 Arginine is synthesized by mammalian cells, but at insufficient rates to meet the
growth needs of the body.
 Amino acids which animals can synthesize are called nonessential amino acids
(Dispensable)
The 20 amino acids
NONESSENTIAL ESSENTIAL
(Dispensable) (Indispensable)
Glutamate Isoleucine
Glutamine Leucine
Proline Lysine
Aspartate Methionine
Asparagine Phenylalanine
Alanine Threonine
Glycine Tryptophan
Serine Valine
Tyrosine Arginine
Cysteine Histidine

Sources of Essential Amino Acids

Most essential amino acids are found in:

Animal meats (both red and white)
Eggs
Dairy products

Vegetarian sources are:

Soy
Peas/beans
Nuts
Seeds
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THE NITROGEN CYCLE AND NITROGEN FIXATION

Nitrogen is needed for amino acid and nucleotides synthesis.

Atmospheric N2 is the ultimate source of biological nitrogen.

How is Nitrogen made available to living organisms?

Through Nitrogen fixation: a few bacteria possess nitrogenase which can reduce N2 to
ammonia.

Nitrogen is recycled in nature through the nitrogen cycle

THE ROLE OF NITROGEN IN THE BIOSPHERE

It is a constituent of:
 All amino acids
 Bases of nucleic acids such as DNA and RNA
 Chlorophyll molecules which are essential in photosynthesis
 Energy transfer compounds (ATP)
Sources of Nitrogen
• Atmospheric
• Inorganic fertilizers
• Nitrogen Fixation
• Animal Residues
• Crop residues
• Organic fertilizers
Forms of Nitrogen
• Urea  CO(NH2)2
• Ammonia  NH3 (gaseous)
• Ammonium  NH4
• Nitrate  NO3
• Nitrite  NO2
• Atmospheric nitrogen N2
• Organic N
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THE NITROGEN CYCLE

Mechanisms of Nitrogen fixation

Biological N2 fixation (symbiotic) - conversion of Atmospheric nitrogen to ammonia –

– e.g in legumes by Rhizobium (bacteria)

Non symbiotic – free living e.g Azobacter (aerobic) & Clostridium (anaerobic), and
Blue green algae, which convert N2 into NH3 and NH4+ ions.

Nitrification is the conversion of Ammonia to Nitrate (by aerobic nitrifying bacteria)

Free ammonia is toxic so in it is converted to nitrate for non-nitrogen fixing plants which
can absorb it.

Nitrosomonas – convert ammonia (NH3) to Nitrite (NO2)

Nitrobacter – convert NO2 to Nitrate (NO3)

Nitrate Reduction – conversion of nitrate to ammonia in higher plants.

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Denitrification – conversion of ammonia (volatilization) or nitrates denitrifying bacteria)

to molecular nitrogen.

AMINO ACID SYNTHESIS

The carbon skeletons of amino acids are all derived from intermediates of the TCA
cycle or glycolysis.

Nitrogen in the form of ammonia is the source of nitrogen for all the amino acids.
The α-amino group of most of the amino acids comes from the transamination reaction
or reductive amination.

Plants and microorganisms have all pathways for the synthesis of amino acids needed
for protein biosynthesis.

Higher animals can synthesize 10 non-essential amino acids from intermediates or from
nitrogen source while the remaining 10 essential amino acids must be obtained from
dietary proteins

1. ASSIMILATION OF AMMONIA
Ammonia is incorporated into Glutamate

2. REDUCTIVE AMINATION (ASSIMILATION OF AMMONIA)

Reductive amination of a-ketoglutarate by glutamate dehydrogenase occurs in plants,
animals and microorganisms. Glutamate dehydrogenase is located in mitochondria in
animals and plants.

Examples:

i) Reductive amination of α -ketoglutarate:

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ii) Reductive Amination of Pyruvate and Oxaloacetate:

+
Pyruvate + NH4 --------------> Alanine
+
Oxaloacetate + NH4 -------> Aspartic Acid

In the first step, α-ketoglutarate, ammonia and NADH are converted by glutamate dehydrogenase to
glutamate, In the second step, the amino group of the newly-formed glutamate is transferred to the α-keto
acid by an aminotransferase, regenerating the α-ketoglutarate, and converting the α-keto acid to the
amino acid.

3. A second important route in assimilation of ammonia is via glutamine

synthetase

Glutamic acid is converted to Glutamine – excess Ammonia is stored

Glutamic acid Glutamine Synthetase Glutamine

Glutamine is a Nitrogen carrier in many biosynthetic reactions

Glutamine acts as reservoir for temporary storage of NH4+

4. TRANSAMINATION REACTIONS

Transamination is the process by which an amino group, usually from glutamate, is

transferred to an α-keto acid, with formation of the corresponding amino acid and α-
ketoglutarate.

In amino acid biosynthesis, the amino group of glutamate is transferred to various α -

keto acids generating α -amino acids

Glutamic acid is the most important source of amino group in the transamination
process because it is synthesized in abundance during reductive amination.
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Examples of a transaminase reactions

 Aspartate donates its amino group, becoming the α -keto acid oxaloacetate.
 α -Ketoglutarate accepts the amino group, becoming the amino acid glutamate.

Or,

 Alanine becomes pyruvate as the amino group is transferred to α-ketoglutarate.

Enzyme is alanine transaminase

Synthesis is best summarized by metabolic schemes which arise from a series of α-keto
acids, namely pyruvate, oxaloacetate and α-keto glutarate.

The biosynthesis of amino acids may therefore be grouped into six biosynthetic families
which are based upon common precursors:

The common metabolic precursors for the synthesis of amino acids include:
1. Oxaloacetate
2. PEP + erythrose-4-phosphate
3. α -ketoglutarate
4. Pyruvate
5. 3-phosphoglycerate
6. Ribose 5-phosphate
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 The nonessential amino acids are synthesized by simple pathways.

 With the exception of tyrosine, all of the non-essential amino acids are
synthesized from intermediates of major metabolic pathways. The carbon
skeletons are traceable to their corresponding α-ketoacids.
 Aspartate, glutamate and alanine can be synthesized by simple transamination
reactions of oxaloacetate, α -ketoglutarate and pyruvate, respectively.
 These reactions are catalyzed by specific amino-transferases.
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5. AMINO ACID BIOSYNTHETIC FAMILIES.

In the illustration below, the metabolic precursors are in blue, amino acids which serve
as precursors for other amino acids are in red and essential amino acids are underlined.

All the steps involve various Enzymes and Co-enzymes in multi step sequences
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Biosynthesis of serine and glycine

Glycine

Major pathway for the formation of Serine begins with 3-PGA an intermediate of
glycolysis. Serine then becomes a precursor for Glycine.

The pathways leading to the synthesis of essential amino acids is generally long
and complex.

Higher animals are unable to make these for example due to the lack of one or two
enzymes in the pathways.

Most complex is the synthesis of phenylalanine, tryptophan and histidine.

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 Higher animals actively oxidize amino acids arising from metabolic turnover of
proteins. This takes place largely in the liver.
 Amino groups have a common terminal fate – excrete ammonia as urea or uric
acid depending on the species.
 In higher plants net direction is towards synthesis rather than oxidation.
 When oxidised free ammonia is converted to amines such as glutamine.
 Transamination and Oxidative deamination constitutes the 1st stage in a.a.
catabolism
 Important products of amino acid. catabolism are keto-acids.
 The Carbon skeleton is then fed into the citric acid cycle (TCA).
 In addition to equilibrating amino groups among available a-keto acids,
transaminases funnel amino groups from excess amino acids to those amino
acids (e.g., glutamate) that can be deaminated.
 Carbon skeletons of de-aminated amino acids can be catabolised for energy, or
used to synthesize glucose or fatty acids for energy storage.
 The role of transaminases is funneling amino N to glutamate, which is
deaminated producing NH4+.
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The 20 amino acids are converted to 7 products which enter the TCA cycle:

 Pyruvate
 Acetyl-Coa
 Acetoacetate
 α-Ketoglutarate
 Succinyl-CoA
 Oxalocetate
 Fumarate
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AMINO ACID METABOLISM and CENTRAL METABOLIC PATHWAYS

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THE PEPTIDE BOND

A peptide bond is a chemical bond formed between two molecules when the carboxyl
group of one molecule reacts with the amino group of the other molecule, releasing a
molecule of water (H2O). This is a dehydration synthesis reaction (also known as a
condensation reaction), and usually occurs between amino acids.
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Alanylglycine, A Dipeptide

Or:

Glycylalanine Alanylglycine
Both are Dipeptides
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POLYPEPTIDE CHAINS