CHEMISTRY OF AMINO ACIDS AND

PROTEINS

Dr Hassan Yankuzo
(MBBS, MSc, PhD)
 Proteins
 Polymers of amino acids joined together by
peptide bonds via condensation reactions.

 Proteins are fundamental basis of the structure

and function of life.

 The most abundant nitrogenous organic molecules in

cells (> 50% of the cellular dry weight)
 Amino Acids

 Building blocks of proteins.

 Only 20 out of 300 amino acids in the

nature are found in proteins

 Amino acids are distinguished by the R

group attached to their α-carbon atoms
 Structure of Amino Acids

All 20 amino acids except Glycine, exhibit the

concept of isomerism.
 Classification of Amino Acids
Amino acids are classified based on their structure (R
group), nutritional requirement, and metabolic fate.

CLASSIFICATION BASED ON R GROUP

Non-polar Aliphatic group e.g. Glycine, Alanine, Valine,
Leucine, Isoleucine and Methionine
Aromatic group e.g. Phenyl Alanine, Tyrosine,
Tryptophan
Polar uncharged group: e.g. Serine, Threonine, Cysteine,
Proline, Asparagine, Glutamine
Positively charged group: Lysine, Arginine, Histidine
Negatively charged group: Glutamate and Aspartate
 Classification based on nutritional
requirement

Essential Amino Acids – cannot be synthesized

by the body, but supplied through diet only.

Non-essential Amino Acids – Synthesized by

the body.
Essential and Non-essential Amino Acids

Essential AAs Non-essential AAs

 Alanine
 Histidine
 Asparagine
 Isoleucine
 Aspartate
 Leucine
 Cysteine
 Lysine
 Glutamate
 Arginine
 Glutamine
 Methionine
 Glycine
 Phenylalanine
 Proline
 Threonine
 Serine
 Tryptophan
 Tyrosine
 Valine

GAGAGA PSCT
PVT TIM HALL
 Classification based on metabolic fate

 Glucogenic – e.g. Arginine, Histidine, Glutamate

Glutamine, Proline, Methionine, Valine, Alanine,
Aspartate, Asparagine, Cysteine, Glycine, Serine,

 Ketogenic – e.g. Leucine and Lysine

 Gluco Ketogenic: Isoleucine, Phenyl Alanine,

Tyrosine, Tryptophan, Threonine
 Nomenclature of Amino acids

Amino acids have two basic symbols:

Three letter word e.g. Ala, Val, Leu, Ile

etc

One letter word e.g. A, V, L, I

 Amino Acids Derivatives
Compounds Amino Acids
Heme Glycine
Histamine Histidine
Melanin, Thyroxine Tyrosine
(T4), Epinephrine, NE,
& Dopamine
GABA Glutamate
Pyruvate Alanine
 Properties of Amino Acids
A. Physical Properties

1. Solubility: All amino acids are soluble in water and

insoluble in organic solvents.

2. Melting points: Amino acids generally melt at higher

temperatures, often above 200 degrees.

3. Taste: Amino acids may be sweet, tasteless

or bitter, e.g. Monosodium glutamate.
 Physical Properties - continued

4.Optical properties: All Amino acids (except glycine)

exhibit isomerism due to their asymmetric carbon.

5.As ampholytes: AAs contain both acidic (COOH)

and basic (NH2) groups at physiological pH.

6.As Zwitterions: Zwitter ion is a hybrid molecule

containing both positive and negative ionic groups
B. Chemical Properties

The general reactions of AAs are mostly due to the

presence of two functional groups namely; Carboxylic
Acid (COOH) and Amino (NH2) groups.

Rxns due to COOH group

Chemical Properties

Reactions due to NH2 group

 Reactions due to COOH group

1. Formation of salts and esters: AAs form salts with

bases (COONa), and esters with alcohols (COOR).

2. Decarboxylation: AAs undergo decarboxylation to

produce corresponding amines. e.g. Histamine,
tyramine and GABA from decarboxylation
of Histidine, Tyrosine and Glutamate respectively

3. Reactions with Ammonia: The carboxyl group of

dicarboxylic AAs react with NH3 to form amide.
Aspartate + NH3 Asparagine
Glutamate + NH3 Glutamine
 Reactions due to NH2 group
4. Transamination: Transfer of an amino group from an
amino acid to a keto acid to form a new amino acid
is known as transamination

5. Oxidative deamination: Aas undergo oxidative

deamination to liberate free ammonia

6. Reaction with Ninhydrin: AAs react with Ninhydrin to

form a purple, blue, or pink colour complex
(Ruhemanns’ purple)

AA + Ninhydrin Keto acid + NH3 + CO2 Ruhemanns’

purple
 Biological importance of Amino Acids
1. Building blocks of proteins: polymerization of
amino acids results in the formation of proteins

2. Biological buffers: AAs being amphoteric, act as

buffers in solutions by donating H+ ions as pH
increases and accepting H+ ions as pH
decreases, thereby resisting changes in pH.

3. Asparagine and glutamine, which are derivatives

of aspartate and glutamate, serve as storage
forms of nitrogen
 Biological importance of Amino Acids

4. Cystine link chains together by forming disulfide

bonds

5. The aromatic rings of Phe, Tyr and Trp help in

electron transfer

6. Formation of glucose: some AAs form glucose by

loosing their amino group

7. Histidine found in the active site of enzymes

results in the formation and breakage of bonds
 Biological importance of Amino Acids

8. Antibiotics: The non-protein AAs are useful

compounds of antibiotics. e.g. Azaserine,
Valinomycin

9. Play a role in nerve transmission, cell growth,

and biosynthesis of porphyrins, purines,
pyrimidines and urea

10. Formation of other compounds: e.g. Tyr

produces thyroxin, adrenalin and melanin.
Glycine forms heme. e.t.c
PEPTIDES AND
PROTEINS
 Twenty AAs are commonly found in
proteins

 Th ey a re l i n ked t o get h er t h ro u gh
peptide bond forming peptides and
proteins

 The chains containing ≤ 50 AAs are

called “Peptides”, while those
containing > 50 AAs are called
“Proteins”
 Formation of a Peptide bond

Carboxylic acid group of one AA (R1) forms a covalent

bond with amino group of another AA (R2) by removal
of a molecule of water to form a dipeptide (i.e. two AAs
linked by one peptide bond).
 Formation of a Peptide bond
 When the dipeptide forms a second peptide
bond with a third AA, a Tripeptide is formed.

 R e p e ti ti on of th i s p r oc e s s g e n e rate s a
polypeptide chain that starts with N-terminal
on the left side and ends with C-terminal on
the right side.
 Formation of a Peptide bond

S p e c i f ic A a s a re t ra n s f e rre d ( b y t R N A ) t o t h e
mitochondria to connect to the growing peptide chain.
 Naming of Peptides

 Polymers composed of 2, 3, 3-10, and several

AA residues are called dipeptides, tripeptides,
oligopeptides and polypeptides respectively.

Examples of peptides
 Dipeptide: e.g. Aspartame, a combination of
aspartate and phenyl Alanine, used as artificial
sweetener to replace sucrose in the sugar
cane
 Naming of Peptides

 Tripeptides: e.g. Glutathione, a combination of

Glu-Cys-Gly that helps in absorption of Aas and
pr otec ts agai n s t h emol ys i s of R BC s by
breaking H2O2 which causes cell damage

 Polypeptide: e.g. Insulin, a hormone containing

51 unique amino acids sequence. Lysozyme,
an enzyme containing 126 amino acids
sequence.
 Cysteine and Disulfide Bonds
 Two cysteine residues joined together by
disulf ide bond forms a dimeric AA known as
Cystine.

 The cysteine residue is strongly hydrophobic

 In proteins, disulfide bonds form covalent links

b/w different parts of a single polypeptide
chain, or b/w two different polypeptide chains.
 PROTEINS
Polymers of Amino acids containing
16% N in addition to C, H and O
 Nitrogen balance
Nitrogen Balance: comparison of the nitrogen a person
consumes with the nitrogen he or she excretes.
 Protein is the only energy nutrient that provides
nitrogen
 Nitrogen Equilibrium: excrete the same amount that is
taken in
 Positive Nitrogen Balance: build new tissue - takes in
more than what is excreted
 Negative Nitrogen Balance: tissues that are
deteriorating.
○ Example: body that is wasting due to starvation
 Major source of protein
Excess Proteins in the diet
 Mostly in developed countries
○ Lack of education about protein needs
 Classification of proteins
Complete proteins - contain all the nine essential amino acids
in adequate proportion required for metabolism. They are
mostly obtained from animal sources such as poultry, beef, milk
, fish, etc.

Incomplete proteins - are those lacking one or more of the nine

essential amino acids. E.g. cereals, legumes, vegetables

Complementary proteins - combination of two or more

incomplete proteins to give a value of one equivalent complete
protein. e.g. combination of legumes (ile, leu, lys) and cereals
(met, tryp)

NB: there is one plant source that contain all the nine essential
amino acids in an adequate proportion, which is the SOYA
BEANS
Structural levels of Protein
Primary Structure
 Linear sequence of amino
acids.
Secondary Structure
 Form helices or sheets
due to their structure.
Tertiary Structure
 A folded protein.
Quaternary Structure
 2 or more polypeptide
chains bonded together.
 Primary structure of proteins
 This refers to the linear sequence of AAs present
in the polypeptide chain

 The unique sequence of Aas in each protein is

determined by the genes contained in DNA.

 Each component AA in a polypeptide chain is

called “residue” or “moiety”.

 By convention, the primary structure of protein

starts from the N-terminal and ends with C-
terminal
 Primary structure of proteins

 Example: Lysozyme has 129 Aas, all of which

are in a very specific order.

 Most genetic diseases (e.g. SCDx) are due to

the abnormalities associated with primary
structure of proteins
 Secondary structure of proteins
 This refers to folded structures that forms
due to interactions b/w hydrogen bonds and
peptide bonds in different parts of the
polypeptide chain.

Hydrogen bonds (although weak), stabilizes the

secondary structures of proteins due to their
large number
 Secondary structure of proteins
 Th e pr ototype ex ampl es of s ec on dar y
structures of protein are Alpha helix (α-helix)
and Beta pleated sheet (β-sheet).

 Both structures are held in shape by

hydrogen bonds b/w the carbonyl oxygen (CO)
of 1 AA and the amino group of another AA.

NB: Secondary structures have helices, sheets

and turns
 Alpha Helix (α-helix)
 α-helical structure and β-sheets, one of the
milestones in biochemistry research, were
proposed by Pauling and Corey in 1951.

 α-Helix is a spiral structure with Aas side

chains extending outward from the central
axis. Each turn of α-Helix have 3.6 AAs, a
distance of 0.54 nm, and a spacing of 0.15 nm
b/w each AA

 α-Helix is stabilized by extensive hydrogen

bonding, and it is formed spontaneously with
the lowest energy.
 Alpha Helix (α-helix)

 All peptide bonds except the first and last in a

polypeptide chain participate in H bonding.

 α-Helix is formed b/w H atom attached to

peptide N, and O atom attached to peptide C
of every fourth AA down the chain.

 Proteomics studies have shown that right

handed α-helices occur in proteins. The left
handed α-helices are theoretically less stable
 Beta pleated sheet (β-sheets)

 β-sheets are formed by single or separate

polypeptide chains arranged in parallel or
antiparallel direction, with additional H-bonds
holding different segments of the polypeptide
chains.

 Example of a β-sheet is two strands of hair

pin connected by a sharp turn
 CLASS EXERCISE

Write short note on the differences

between α-helix and β-pleated sheet of
secondary protein structure
Tertiary structure of proteins

 This refers to the 3-dimensional folding

structure of protein.

 It is a compact structure with hydrophobic

s i d e c h a i n s h e l d i n t h e i n t e r i o r, a n d
hydrophilic R groups on the surface of the
protein molecule.

 This type of arrangement ensures stability of

the protein molecule. e.g. disulf ide bridges
b/w neighboring R groups of cysteine AAs.
 Tertiary structure of proteins

Peptide bonds, disulf ide bonds, hydrogen bonds,

hydrophobic and ionic interactions stabilizes the
tertiary structure of proteins.

Tertiary structure determines the activity of a

particular protein. Example:

Globular proteins: spherical shape – include

insulin, enzymes and antibodies

Fibrous proteins: Long thin f ibers – found in the

hair, skin, nails. e.g. Keratin
 Quaternary structure of proteins
 This refers to the monomers of polypeptide chains that
may be identical or unrelated, held together by similar
bonds as in the tertiary structure of proteins.

 Examples of oligomeric proteins are Hb, LDH, and

aspartate transcarbomylase. They play a vital role in the
regulation of metabolism and cellular function.

 Io nic o r e le c t r o st at ic b o nd s ar e fo r m e d b y t he
interaction between negatively charged groups of acidic
Aas (COO) and positively charged groups (NH3) of basic
Aas.
 Quaternary structure of proteins

 Hemoglobin for example, has 2 identical α

and β-chains, each with iron-containing heme
group that binds oxygen.

 The α and β-chains are very similar but

distinguishable in both primary structure and
folding.
 Biological functions of proteins

 Structural function e.g. keratin of hair and

nails, collagen of bone

 As Enzymes e.g. Hexokinase, Pepsin.

 As blood transporters e.g. serum albumin,

Hemoglobin

 As Hormones e.g. Insulin, growth hormone

 Contractile function e.g. Actin, Myosin

 Storage function e.g. Ovalbumin, glutelin.

 As Genetic influencers e.g. Nucleoproteins

 D e f e n s e f u n c ti on e .g . S n ake v e n om s ,
Immunoglobulins

 As receptors for hormones, viruses etc

Thank you