EVELYN HONE COLLEGE OF APPLIED SCIENCE AND

TECHNOLOGY
SCHOOL OF HEALTH SCIENCES
DEPARTMENT OF BIOMEDICAL SCIENCES
METABOLIC BIOCHEMISTRY

Dr. G.H Msoni

 OBJECTIVES
• By the end of the topic, students must;
• Define amino acids
• Know the various classes of amino acids
• Know the function of amino acids
• Know the uncommon amino acids
• Define proteins
• Know the function of proteins
• Know the levels of protein structure
 AMINO ACIDS:
CHARACTERISTICS & FUNCTIONS

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 OUTLINE
• Importance of Amino Acids
• History of Amino Acids
• Zwitterion
• Chirality
• General properties conferred by side chain
• Groupings of amino acids
• Uncommon amino acids
• Essential and Non-essential amino acids

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 BIOMEDICAL IMPORTANCE OF AMINO ACIDS

 units or building blocks for polypeptide chains of proteins.

 Amino acids and their derivatives participate in cellular

functions such as nerve transmission and biosynthesis of
porphyrins, purines, pyrimidines and urea.

 Short polymers of amino acids called peptides perform

prominent roles in the neuroendocrine system as hormones,
hormone-releasing factors, neuro-modulators, or neuro-
transmitters.

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 In nature there are over 300 naturally occuring amino acids

 Only 20 of these occur in proteins(std amino acids)

 Some proteins contain amino acid derivatives that are

generated after incorporation of the amino acid into the protein
molecule

 Several free L-α-amino acids fulfill important roles in metabolic

processes. Examples include:
-ornithine, citrulline, & argininosuccinate that
participate in urea synthesis;
-tyrosine in formation of thyroid hormones;
- glutamate in neurotransmitter biosynthesis.

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 Nineteen of these are α-amino acids with a primary amino
group (–NH3+) and a carboxylic acid (carboxyl; –COOH)
group attached to a central carbon atom.
 This is called the α-carbon atom (C) because it is adjacent to
the carboxyl group. Also attached to the C atom is a hydrogen
atom and a variable side-chain or ‘R’ group.

EXCEPTION to this general structure is proline, which has a

secondary amino group hence is an α-imino acid.

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 HISTORY
• The first to be discovered was asparagine, in 1806. The last of
the 20 to be found, threonine, was not identified until1938.
• All the amino acids have trivial or common names, in some
cases derived from the source from which they were first
isolated.
• Asparagine was first found in Asparagus spp,
• Glutamate in wheat gluten;
• Tyrosine was first isolated from cheese (its name is derived
from the Greek tyros, “cheese”);
• Glycine (Greek glykos, “sweet”) was so named because of its
sweet taste.

• The names of the amino acids are often abbreviated, either to

three letters or to a single letter.

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 Amino acids may have positive, negative or zero
charge (Zwitterions).
An α- amino acid consists of - an amino group
All bonded to an α-
- a carboxyl group carbon. This carbon
- a hydrogen atom atom is called α- carbon
- a distinctive R group because its adjacent to
(side chain) the carboxyl (acidic)
group

NH 2 N H +3

H C CO OH H C CO O –

R R

Un-ionized form of an Dipolar ion (Zwitterion)

amino acid form of an amino acid

**Amino acids in solution at physiologic pH (pH 7.4) are predominantly

dipolar where the amino group is protonated (–NH3+) and the carboxyl group is
dissociated (–COO-)**
**Biological pH is 7.00**.
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• All of the amino acids, except for glycine, have four different
groups arranged tetrahedrally around the central C atom.

• This is known as an asymmetric center or chiral center and

has the property of chirality.

• Because of the tetrahedral arrangement of the bonding

orbitals around the α-carbon atom, the four different groups
can occupy two unique spatial arrangements-hence two
possible stereoisomers.

• Since they are non-superimposable mirror images of each

other, the two forms represent a class of stereoisomers called
enantiomers

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• The standard 20 amino acids differ only in the structure of the
side-chain or amino acids ‘R’ group.
• Are subdivided into smaller groupings on the basis of
similarities in the properties of their side-chains.

• They display different physiochemical properties

• Some are acidic; others are basic.

• Some have small side-chains, others large, bulky side-chains.

Some have aromatic side-chains, others are polar.

• Some confer conformational inflexibility.

• Others can participate either in hydrogen or covalent bonding.

• **Some are chemically reactive.** 11
• The charged functional groups confers property of solubility
in—polar solvents such as water and ethanol and insolubility in
nonpolar solvents such as benzene, hexane, or ether.

• High amount of energy required to disrupt the ionic forces

that stabilize the crystal lattice account for the high melting
points of amino acids (> 200 °C).

• Amino acids do not absorb visible light and thus are

colourless. However, tyrosine, phenylalanine, and especially
tryptophan absorb high-wavelength (250–290nm) ultraviolet
light.

• Tryptophan therefore makes the major contribution to the ability

of most proteins to absorb light in the region of 280 nm.

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 Aliphatic side chains Smallest & simplest structured amino
H CH COO –
Glycine acid owing to H-atom-does not exist
NH+
3
exhibit chirality. Often occurs where
peptides bend sharply.
CH 3 CH C OO –
Alanine
NH+
3

CH 3
Valine CH CH C OO –
CH 3
NH+
3 Chemically unreactive and
have hydrophobic side
CH 3 chain-have aversion to
Leucine CH CH 2 CH C OO–
CH 3 water and like to cluster.
NH+
3 Occur primarily in the
interior of cytosolic
CH 3 proteins.
CH 2
Isoleucine CH CH C OO –
CH 3
NH +
3

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Amino acids containing hydroxyl (OH) side chains
Hydroxylated. More hydrophilic and reactive
CH 2 CH CO O–
Serine than alanine.The primary alcohol group is a
OH NH + nucleophile that can function during
3
enzymatic catalysis
CH 3 CH CH CO O –
Threonine Hydroxylated. More hydrophilic and
OH NH+
3
reactive than valine
**The –OH groups of these amino acids can participate in enzyme regulation**

Side chains containing sulfur atoms

Contains a sulfhydryl group (-SH). ?
Hydrophobic. -SH is highly reactive capable
of reacting with another cysteine to form a
Cysteine CH 2 CH CO O– disulfide bond. The primary thio (–SH)
SH NH+ group is a nucleophiles and can function
3
during enzymatic catalysis
CH 2 CH 2 CH CO O–
Methionine N H+ Contains a sulfur atom in a thioester
S CH 3
3 linkage (-S-CH3). Is Hydrophobic

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Side chains containing acidic groups on their amides
Side chain nearly always negatively
Aspartic acid – OOC CH 2 CH CO O–
charged at physiological pH.
N H+
3

Asparagine NH2 C CH 2 CH CO O–

O N H+
3

Glutamic acid – OOC CH 2 CH 2 CH CO O– Side chain nearly always negatively

charged at physiological pH.
N H+
3
NH 2 C CH 2 CH 2 CH CO O–
Glutamine
O NH +
3

Uncharged derivatives of glutamate and aspartate are glutamine and

asparagine respectively, which contain a terminal amide group in place of a
carboxylate • Are therefore polar and de-
protonated amino acids.
• The charged R groups
stabilize specific protein
conformation via ionic
interactions, or salt bonds15
 Side chains containing basic groups

H N CH 2 CH 2 CH 2 CH CO O–
Arginine
C +
NH 2 NH+ Very polar side chains
3
which render them highly
NH 2
hydrophilic. Are positively
Lysine CH 2 CH 2 CH 2 CH 2 CH CO O– charged at neutral pH.
NH3+ NH+
3

Equally polar and hydrophilic

CH 2 CH CO O–
Histidine but may be positively charged
HN N N H+ at neutral pH depending on
3
conditions. Plays an important
role in enzymatic catalysis
functioning as either a base or
an acid catalyst at pH 7.0

The charged R groups stabilize specific protein conformation

via ionic interactions, or salt bonds

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 Side chains containing aromatic rings
Phenyl ring attached to a
Phenylalanine CH 2 CH CO O – methylene group. Hydrophobic
NH +
3

Contains a -OH group which

Tyrosine HO CH 2 CH CO O – makes it less hydrophobic than
Phe (F). OH is also reactive,
NH +
3 paticipates in enzyme regulation.

CH 2 CH CO O – Indole ring joined to a

methylene group.
NH+
Tryptophan 3 Hydrophobic
N

Occur primarily in the interior of cytosolic proteins The aromatic rings contain
delocalised electron clouds which enable them to interact other systems and
transfer electrons. They absorb high-wavelength (250– 290 nm) ultraviolet light.
Imino acid Has an aliphatic side chain bonded to both the
+ CO O –nitrogen and α carbon atoms. It is hydrophobic
Proline N but, with its aliphatic side-chain bonded back on to
H the amino group, it is conformationally rigid. Often
2
found on bends of folded proteins. 17
Non polar amino acids Polar amino acids
Alanine,Ala,A Arginine,Arg,R
Isoleucine,Ile,I Asparagine,Asn,N
Leucine,Leu,L Aspartic acid,Asp,D
Methionine,Met,M Cysteine,Cys,C
Phenylalanine,Phe,F Glutamic acid,Glu,E
Proline,Pro,P Glutamine,Gln,Q
Tryptophan,Trp,W Glycine,Gly,G
Valine,Val,V Histidine,His,H
Lysine,Lys,K
Serine,Ser,S
Threonine,Thr,T
Tyrosine,Tyr,Y
Please note the three letter and one letter abbreviation for
each 19 amino acids and 1 imino acid. 18
 Humans can synthesize 12 of the 20 common amino acids from
the amphibolic intermediates of glycolysis and the citric acid cycle
- 9 from amphibolic intermediates
- 3 (cysteine, tyrosine and hydroxylysine) from
nutritionally essential amino acids

Essential amino acids must be supplied in the diet

Essential Non-essential
Arginine* Alanine
Histidine Asparagine
Isoleucine Aspartate
Leucine Cysteine*
Lysine Glutamate
Methionine Glutamine*
Phenylalanine Glycine*
Threonine Proline*
Tryptophan Serine
Valine Tyrosine*
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 Uncommon Amino Acids Also Have Important Functions
In addition to the 20 common amino acids, proteins may contain
residues created by modification of common residues already
incorporated into a polypeptide:

a)4-hydroxyproline, a derivative of proline, found in plant cell

wall proteins, collagen

b)5-hydroxylysine, derived from lysine-also found in collagen.

c) 6-Nmethyllysine, is a constituent of myosin, a contractile

protein of muscle.

d)carboxyglutamate, found in the blood clotting protein

prothrombin and in certain other proteins that bind calcium ions as
part of their biological function.
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e)more complex,desmosine, a derivative of four L residues,
which is found in the fibrous protein elastin.

f)Selenocysteine is a special case. This rare amino acid residue

is introduced during protein synthesis rather than created through
a post-synthetic modification. It contains selenium rather than
the sulfur of cysteine. Actually derived from serine. Is a constituent
of just a few known proteins.

g)Some 300 additional amino acids have been found in cells.

They have a variety of functions but are not constituents of
proteins. E.g. Ornithine and citrulline.

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 Amino Acids Can Act as Acids and Bases
When an amino acid is dissolved in water, it exists in solution as the
dipolar ion, or zwitterion (German for “hybrid ion)
A zwitterion can act as either an acid (proton donor):

OR
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a base (proton acceptor):

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 ANY
QUESTIONS ???????
???????????????????

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TRANSAMINATION AND DEAMINATION
 Proteins-
Characteristics & Functions

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 Biological Functions

1. Enzyme catalysts
Nearly all chemical reactions in biological systems are
catalyzed by enzymes-nearly all known enzymes are
proteins

2. Transport and storage

Many small molecules and ions are transported by specific proteins
eg Haemoglobin transports oxygen
Iron is stored in the liver as ferritin
Lipoproteins transports fats, steroids, phosholipids

3. Coordinated motion
Muscle contraction is accomplished by sliding motion of two kinds
of protein filaments-actin & myosin
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 Biological Functions Cont…….
4. Mechanical/Structural support
Tensile strength of the skin and bone-due to the presence of
collagen

5. Immune/Defence Proteins
Antibodies/immunoglobulins

6. Generation and transmission of nerve impulses

Receptor proteins play a role in transmission of impulses

7. Control of growth and differentiation

-Growth factor proteins play a role in growth and differentiation
-Hormones coordinate activities of different cells in multicellular
organisms

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 Amino acids sequence determines:

– how a protein folds up into its unique three-dimensional

structure

– and this in turn determines the function of the protein

– cellular location – certain sequences serve as signals that

target proteins for export or tissue distribution

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 Levels of Protein Structure
Primary Structure
• Is a linear sequence of amino acids linked together by peptide bonds
or amide bonds-between the α -amino group of one amino acid and
the α-carboxyl group of another.

+H3N-serine–leucine–phenylalanine-COO- OR Ser-Leu-Phe
OR S-L-F

Convention has it that peptide chains are written down with the
free α-amino group on the left, the free α-carboxyl group on the
right and a hyphen (-) between the amino acids to indicate the
peptide bonds. 30
-2 amino acids joined by a peptide bond to form a dipeptide
-3 amino acids joined by 2 peptide bond to form a tripeptide
-Upto 25 amino acids -form a oligopeptide
-Peptides with more than 25 amino acid RESIDUES are termed
polypeptides
****If MW is more than 10,000, polypeptides may be referred to as
proteins**** 31
 Some naturally occurring peptides have biologically important effects
(a)Oxytocin (9 residues)–stimulates uterine contractions

(b)Bradykinin (9 residues)–inhibits inflammation in tissues

(c)Thyrotropin- releasing factor

(d)Mushroom toxin amanitin is also a small peptide, as are some

antibiotics.

Slightly larger peptides include:

(e)Insulin with two polypeptide chains (30 and 21 residues) held

together by disulfide bonds

(f)Glucagon (29 residues) – counters the effects of insulin

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 Protein Secondary structure
• Secondary structure in a protein refers to the regular folding of
regions of the polypeptide chain giving rise to recurring structural
patterns. 2° may exhibit few irregularities (e.g. random coils)

Types of 2° Structures

i)α-Helix,

ii)β-Pleated Sheets

iii)Random coils (irregular)

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 The α-Helix

Is a common protein
secondary structure

The polypeptide is
tightly wound around
an imaginary axis
drawn longitudinally
through the middle of
the helix, and the R
groups of the amino
acids protrude
outward from the
helical backbone

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• Certain amino acids are more often found in α -helices than others.

• Pro is rarely found in α-helical regions as it cannot form the correct

pattern of hydrogen bonds due to the lack of a hydrogen atom on its
nitrogen atom.

• For this reason, Pro is often found at the end of an α-helix, where it
alters the direction of the polypeptide chain and terminates the helix.

• Different proteins have a different amount of the polypeptide chain

folded up into α-helices. For example, the single polypeptide chain of
myoglobin has eight α-helices.

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 β- pleated sheets

• Are stabilized by hydrogen bonding between β strands

• The hydrogen bonds form between the peptide bonds either in different polypeptide chains or in different
sections of the same polypeptide chain.

• The planarity of the peptide bond forces the polypeptide to be pleated with the side-chains of the amino
acids protruding above and below the sheet.

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.
• The pleated sheet is extended into a zigzag (pleated) formation rather the being tightly
coiled as in the α- helix

• Adjacent polypeptide chains in β-pleated sheets can be either parallel or antiparallel

depending on whether they run in the same direction or in opposite directions,
respectively.
• Role of β-pleated sheets is to provide strength and rigidity in many structural proteins,
such as silk fibroin, which consists almost entirely of stacks of antiparallel β-pleated sheets.

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38
39
 β- turns
• In globular proteins, which have a compact structure, nearly one
third of the amino acid residues are in turns or loops where the
polypeptide chain reverses direction making a hairpin or –turn.

- These are the connecting elements that link successive runs of α and
β conformations

In these β-turns, the carbonyl oxygen of one amino acid is

hydrogen bonded to the hydrogen on the amino group of the
fourth amino acid 40
 β- turns cont…..

• These turns are often found connecting the ends of antiparallel β-

pleated sheets.

• Regions of the polypeptide chain that are not in a regular secondary

structure are hence said to have a coil or loop conformation.

• About half the polypeptide chain of a typical globular protein will be

in such a conformation.

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Protein structure showing α-helix and β sheet conformations

α-helix

β sheets

Random coils

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 Protein Tertiary Structure

• Refers to the entire three dimensional conformation of a

polypeptide- it comprises of helices, sheets, bends, turns and loops -
assembled to form domains and how these domains relate spatially
to one another.

• The polypeptide chain folds spontaneously so that the majority of its

hydrophobic side-chains are buried in the interior, and the majority
of its polar, charged side-chains are on the surface.

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 Protein Tertiary Structure cont…..

• Once folded, the three-dimensional, biologically active (native)

conformation of the protein is maintained by:

• i)hydrophobic interactions ii)electrostatic forces,

• iii)hydrogen bonding iv)covalent disulfide (if present)

• The electrostatic forces include salt bridges between oppositely

charged groups.

• Multiple weak van der Waals interactions occur between the tightly
packed aliphatic side-chains in the interior of the protein.

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 Protein Quaternary Structure

• Quaternary structure comprises 2 or more polypeptide chains united

by forces other than covalent bonds ( i.e. not peptide or disulfide
bonds)

• The forces that stabilize these aggregates are hydrogen bonds and
electrostatic bonds formed between residues on the surface of the
polypeptide chains

• Such proteins are called oligomers and the individual polypeptides of

which they are composed are protomers
(monomers or subunits)

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 Protein Quaternary Structure

• The most commonly encountered oligomeric proteins contain 2 or 4

protomers and are termed dimers and tetramers respectively

• Homodimers contain two copies of the same polypeptide chain,

while in a heterodimer the polypeptides differ

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FOUR LEVELS OF PROTEIN STRUCTURE

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 Some Proteins Contain Chemical Groups Other Than Amino Acids

Proteins with amino acid residues & no other chemical constituents-

simple proteins.

Proteins containing permanently associated chemical components

&amino acids-called conjugated proteins.

The non–amino acid part of a conjugated protein is usually called its

prosthetic group.

Conjugated proteins are classified on the basis of the chemical nature

of their prosthetic groups

For example, lipoproteins contain lipids, glycoproteins contain sugar

groups, and metalloproteins contain a specific metal.

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 HOW PROTEIN
STRUCTURE IS RELATED
TO FUNCTION
• The three-dimensional conformation of proteins
correspond with the wide diversity of function.
Typical examples are:
enzymes
collagen
haemoglobin and myoglobin
HAVE YOU MET THE SET
OBJECTIVES ??????????????
?????????????

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