Kwame Nkrumah University of

Science & Technology, Kumasi, Ghana

AMINO ACID METABOLISM

Dr Max Efui Annani-Akollor

Dept of Molecular Medicine

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 Lecture Outline
• Macromolecules Metabolized
• Amino acids (aa)
• Unusual aa
• General reactions of aa
– Decarboxylation
– Transamination
– Oxidative deamination
– Transdeamination

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 Learning Objectives
• Know the basic structure of aa
• Differentiate between aa based on side chain’s electronic
charge, polarity and the body’s nutritional requirement
• Understand the principle behind general reactions
undergone by aa’s

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Macromolecules
Metabolized

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 Dynamics of Protein
And Amino Acid Metabolism

Dietary Proteins Digestion to Amino Acids

Transport in Blood to Cells

Protein Synthesis Functional Proteins

Amino Acids Protein Degradation In

Proteasomes Following
Tagging With Ubiquitin
Metabolites
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 Amino Acids
• These are the basic structural units of proteins
• There are twenty common amino acids found in proteins
• At the centre of a amino acid molecule is a tetrahedral carbon atom
referred to as the alpha carbon (Cα)

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 BASIC AMINO ACID STRUCTURE
carboxyl group

amino group

 α-carbon is chiral (except for glycine)

 at pH 7.0 uncharged amino acids are zwitterions a-carbon
side chain
 amino acids have a tetrahedral structure
 The α-carbon atom is covalently bonded to an amino group (NH2) on one side
and a carboxyl group (COOH) on the other side
 A third bond is always to a hydrogen, and the fourth bond is to a variable side
chain (R)

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The 20
amino
acids

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 PROPERTIES OF AMINO ACIDS
•Capacity to polymerize
•Novel acid-base properties
•Varied structure and chemical functionality
•Chirality
•Differ from each other by the R group which varies in structure, size and
electrical charge
•The R group also influences the solubility of the amino acid in water
•The common amino acids may be classified into five main classes based on
the reactivities of their R groups as follows:
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 Aliphatic Non-polar
• This group consists of:
• Glycine (Gly, G)
• Alanine (Ala, A)
• Valine (Val, V)
• Leucine (Leu, L)
• Isoleucine (Ile, I)
• Proline (Pro, P)
• Methionine (Met, M)

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 Aromatic
•All very hydrophobic
•All contain aromatic group
•Absorb UV at 280 nm
•Phenylalanine (Phe, F)
•Tyrosine (Tyr, Y) – -OH ionizable (pKa = 10.5), H-Bonding
•Tryptophan (Trp, W) – bicyclic indole ring, H-Bonding

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 Polar Uncharged
•Polar side groups, hydrophillic , can form hydrogen bonds
•Hydroxyls of Ser and Thr
•weakly ionizable
•Serine (Ser, S) –
•looks like Ala with a -OH
•Threonine (Thr, T) –
•2 chiral carbons
•Asparagine (Asn, N) –
•amide of aspartic acid
•Glutamine (Gln, Q) –
•amide of glutamic acid

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 Polar Negatively Charged
Aspartate (Asp, D)
Glutamate (Glu, E)
•Contain carboxyl groups
• (weaker acids than α-carboxyl-group)
•Negatively charged at physiological pH,
• present as conjugate bases
• (therefore –ate not –ic acids)
•Carboxyl groups function as nucleophiles in
some enzymatic reactions

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 Polar Positively Charged
• Lysine (Lys, K)
• Arginine (Arg, R)
• Histidine (His, H)

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 Essential and Non-essential Amin Acids groupings
based on nutritional requirement
•Essential Amino acids: unable to be
synthesize by body as they must
obtained from food and their sources
are plants and microbes.
•Non-essential Amino acids: if they
are not supplied in our diet the body
can synthesize them

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 Essential and Non-essential Amin Acids groupings
based on nutritional requirement
•Arg, Met and Phe are considered essential for reasons not directly
related to lack of synthesis.
•Arg is synthesized by mammalian cells at a rate that is insufficient to
meet the growth needs of the body and majority that is synthesized is
cleaved to form urea.
•Met is required in large amounts to produce cysteine if the latter
amino acid is not adequately supplied in the diet.
•Phe is needed in large amounts to form tyrosine if the latter is not
adequately supplied in the diet
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 Grouping based on catabolic intermediates

•Classified glucogenic and ketogenic types depending on the metabolic

intermediates they generate on catabolism
•Glucogenic amino acids are catabolized to pyruvate, α-ketoglutarate,
succinyl CoA, fumarate or OAA. E.g Ala, Asn, Asp, Arginine, Cys, Gln,
His, Met, Pro, Thr and Val
•Ketogenic amino acids are catabolized to ACoA or acetoacetyl CoA
•Examples of purely ketogenic amino acids are Leucine and Lysine
•Isoleucine, Phe, Trp, Tyrosine are both glucogenic and ketogenic
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 AMINO ACIDS
METABOLIC CATEGORIES:
GLUCOGENIC, KETOGENIC, OR
GLUCOGENIC AND KETOGENIC

•Except for lysine and leucine

other aa’s are at least partly
glucogenic.
•Lysine and leucine are the
only amino acids that are
solely ketogenic, giving rise
only to acetylCoA or
acetoacetylCoA
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 Unusual Amino Acids
•A variety of unusual amino acids are found in minor amounts in
proteins and nonprotein compounds
•These unusual amino acids found in proteins result from
modifications of the common amino acids (hydroxyproline, ornithine,
norleucine)
•In a few cases these amino acids are incorporated into polypeptide
chains during synthesis
•The unusual amino acids found in nonprotein compounds are
extremely varied in type and are formed by a number of different
metabolic pathways
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 General Reactions of Amino Acids
• Amino acids are decarboxylated to amines
• Some of the amines formed have very important physiological roles

• Histamine stimulates gastric secretion and involved in immune response

(itching)
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 • DOPA → Dopamine + CO2

• Dopamine is an intermediate in the formation of adrenaline, a

vasoconstrictor
• Is the “feel good” neurotransmitter

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• 5 hydroxy tryptophan → 5 hydroxy tryptamine + CO2
• Serotonin is a neurotransmitter
mediating mood, memory..

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 Transamination
•Transamination involves the transfer of an amino group from an amino acid
to a keto-acid to form the corresponding amino acid
•The reaction is catalyzed by amino transferases which require pyridoxal
phosphate (PLP), a derivative of vitamin B6 as a prosthetic group
•PLP functions as the intermediate carrier of amino groups at the active site
of the aminotransferase
•PLP undergoes reversible transformation between the aldehyde form and
the aminated form, pyridoxamine phosphate
•Transamination reactions are classic examples of bimolecular ping-pong
reactions. Examples of aminotransferases are AST and ALT
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•In mammals, all alpha amino acids except lysine and threonine can be
transaminated
•Proline, which has a secondary amino group, cannot participate in PLP
dependent reactions including transamination and decarboxylation
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 Oxidative Deamination
• The oxidative deamination of glutamate occurs in the mitochondria
of the liver yielding ammonia ions
• L-Glutamate +H2O ↔ α-ketoglu + NH4+
• This reaction is catalyzed by glutamate dehydrogenase which is a
complex allosteric enzyme

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 Role of Glutamate dehydrogenase

• Its allosteric activators are GDP and ADP and the allosteric inhibitors are
GTP and ATP. Thus whenever the hepatocytes require fuel from the citric
acid cycle, glutamate dehydrogenase activity increases
• On the other hand when ATP and GTP accumulate, oxidative deamination
of glutamate is inhibited
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 Transdeamination
•The combined action of the
aminotransferases and glutamate
dehydrogenase is referred to as
transdeamination
•The coupling of oxidative
deamination with transamination
of L-glutamate creates an avenue
for deaminating all amino acids

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