PROC2048 BIOCHEMICAL ENGINEERING

WEEK 2

MACROMOLECULES OF LIFE
A/PROF DONALD WLODKOWIC
WHAT CELLS ARE MADE FROM?
ESSENTIAL CHEMICAL COMPONENTS OF LIFE
99% of total number of atoms and 96% of weight
0.9% of total number of atoms
<0.1% of total number of atoms (trace elements)
CHEMICAL COMPOSITION OF A CELL
BUILDING BLOCKS OF CELLS
FOUR CLASSES OF MACROMOLECULES
ARE RESPONSIBLE FOR EXISTENCE OF ALL LIVING SYSTEMS
Most cellular structures are made
of ordered arrays of polymers
called macromolecules

The macromolecules that are

responsible for most of the form
and order of living systems are
generated by the polymerization
of small organic molecules

Important macromolecules in
the cell include proteins, nucleic
acids, polysaccharides and
lipids.
FOUR CLASSES OF MACROMOLECULES
ARE BUILD FROM RESPECTIVE 4 CLASSES OF MONOMERS
The repeating units are called
monomers such as
• sugars present in
polysaccharides
• amino acids present in
proteins
• nucleotides present in
nucleic acids
• fatty acids & glycerol present
in lipids
SYNTHESIS OF MACROMOLECULES
DEHYDRATION SYNTHESIS (CONDENSATION)
Macromolecules are always
synthesized by the stepwise
polymerization of
monomers

The addition of each

monomer occurs by the
removal of a water molecule
= condensation reaction /
dehydration synthesis
DEHYDRATION SYNTHESIS
IS ENERGETICALLY UNFAVOURABLE (REQUIRES ENERGY)
DEGRADATION OF MACROMOLECULES
MACROMOLECULES ARE DISASSEMBLED BY HYDROLYSIS

Degradation of polymers
occurs via hydrolysis,
breaking the bond
between monomers
through addition of one
H+ and one OH−
(a water molecule)
HYDROLYSIS
IS ENERGETICALLY FAVOURABLE
SELF-ASSEMBLY
INTERACTIONS TO FORM MACROMOLECULAR ASSEMBLIES

The principle of self-assembly

states that information needed
to specify the folding of
macromolecules and their
interactions to form complex
structures is inherent in the
polymers themselves

Proteins called molecular

chaperones are sometimes
needed to prevent incorrect
folding
MACROMOLECULAR ASSEMBLIES
SELF-ASSEMBLY IS ALWAYS HIERARCHICAL
Hierarchical assembly is the Biological structures are
dependence on subassemblies almost always assembled
that act as intermediates of the hierarchically
process of assembly of
increasingly complex structures
PROTEINS
PROTEINS FORM MOST OF THE CELL MASS
MOST ABUNDANT MACROMOLECULES IN CELLS
PROTEIN FUNCTONS
CAN BE CLASSIFIED INTO NINE MAJOR CLASSES
• Enzymes serve as catalysts, increasing the rates of
chemical reactions
• Structural proteins—physical support and shape
• Motility proteins—contraction and movement
• Regulatory proteins—control and coordinate cell function
• Transport proteins—move substances into and out of cells
• Signalling proteins—communication between cells
• Receptor proteins—enable cells to respond to chemical
stimuli from the environment
• Defensive proteins—protect against disease
• Storage proteins—reservoirs of amino acids
AMINO ACIDS
ARE BASIC MONOMERS AND BUILDING BLOCKS OF PROTEINS
• Every amino acid has the
same basic structure
• All amino acids except
FUNCTION CARBOXYL GROUP
AMINE GROUP GROUP
glycine have an
asymmetric α carbon
atom
N-TERMINUS C-TERMINUS
• Each has a unique side
chain, called an R group
• The specific properties of
amino acids depend on
the nature of their R groups
AMINO ACIDS - 20 TYPES IN TOTAL
FUNCTIONAL R GROUPS GIVE UNIQUE CHARACTERISTICS

• 20 amino acids in
existence
• build around the same
core structure
• can be liked in a standard
way to any other amino
acid (peptide bond)
• functional (R) groups
give amino acids
distinctive chemical
character
PEPTIDE BOND
CONNECTS ANY TWO AMINO ACIDS TOGETHER

Amino acids are linked

together stepwise into a
linear polymer by
dehydration (or
condensation) reactions

As the three atoms

comprising the H2O are
removed, a covalent C—N
bond (a peptide bond) is
formed
POLYPEPTIDES
LONGER AMINO ACID CHAINS HAVE DIRECTIONALITY
Because of the way peptide
bonds are formed,
polypeptides have
directionality

The end with the amino

group is called the N- (or
amino) terminus

The end with the carboxyl

group is called the C- (or
carboxyl) terminus
POLYPEPTIDES NEED TO FOLD IN 3D SPACE
TO FORM STABLE AND BIOLOGICALLY ACTIVE PROTEINS
The immediate product of amino acid Unfolded
polymerization is a polypeptide polypeptide

However, a polypeptide does not

become a protein until it has assumed a
unique, stable, three-dimensional
conformation and is biologically
active Folded
protein
Many proteins spontaneously fold into
their biologically functional state
POLYPEPTIDES NEED TO FOLD IN 3D SPACE
TO FORM STABLE AND BIOLOGICALLY ACTIVE PROTEINS

Proteins are composed of a

nonrandom series of amino acids

Amino acid sequence determines

the three-dimensional structure,
and thus the function, of a
protein

With 20 different amino acids, a

nearly infinite variety of protein
sequences is possible
LEVELS OF PROTEIN STRUCTURE
FOLDING FROM LINEAR POLYPEPTIDES TO 3D COMPLEXES

LEVEL 1 LEVEL 2 LEVEL 3 LEVEL 4

LEVELS OF PROTEIN STRUCTURE
FROM LINEAR POLYPEPTIDES TO 3D COMPLEXES
PROPER 3D PROTEIN CONFORMATION
RELIES ON PROPER FOLDING FROM LEVEL 1 - 4
ALPHA HELIX & BETA PLEATED SHEET
STABILISATION OF SECONDARY PROTEIN STRUCTURE
PROTEIN CONFORMATION AND STABILITY
IS STABILISED BY SEVERAL KEY INTERACTIONS

Non-covalent interactions
• Hydrogen bonds
• Ionic bonds
• Van der Waals interactions
• Hydrophobic interactions

Covalent interaction
• Disulfide bonds - form
between the sulfur atoms of
two cysteine residues
PROTEIN DENATURATION
UNFOLDING ALWAYS LEADS TO LOSS OF BIOLOGICAL ACTIVITY
The unfolding of
polypeptides, denaturation,
leads to loss of biological
activity (function)

When denatured proteins

are returned to conditions
in which the native
conformation is stable, they
may undergo renaturation,
a refolding into the correct
conformation
NATIVE PROTEIN CONFORMATION
MOST STABLE POSSIBLE THREE-DIMENSIONAL STRUCTURE
Proteins can be divided into two broad categories
Fibrous proteins - have extensive regions of secondary
structure, giving them a highly ordered, repetitive structure
Examples include: Keratin proteins of hair and wool, Collagen
found in tendons and skin

Globular proteins - most proteins are globular proteins that are

folded into compact structures. They can be mainly α helical,
mainly β sheet, or a mixture of both structures
Each type of globular protein has its own unique tertiary structure
Most enzymes are globular proteins
NATIVE PROTEIN CONFORMATION
MOST STABLE POSSIBLE THREE-DIMENSIONAL STRUCTURE
Fibrous proteins Globular proteins
PROTEIN DOMEINS
A DISCRETE, LOCALLY FOLDED UNIT OF TERTIARY STRUCTURE
A domain is a discrete, locally
folded unit of tertiary structure,
usually with a specific function

Proteins with similar functions

often share a common domain

Proteins with multiple functions

usually have a separate domain
for each function, like modular
units from which globular proteins
are constructed
NUCLEIC ACIDS
NUCLEIC ACIDS
INFORMATIONAL MACROMOLECULES
Nucleic acids are called informational macromolecules because
they store, transmit, and express genetic information

The linear sequence of four kinds of nucleotide monomers in

each is non-random and carries genetic information

This information is needed to specify the precise amino acid

sequences of proteins

Two types of nucleic acids: DNA - deoxyribonucleic acid, and

RNA -ribonucleic acid.
NUCLEIC ACIDS
INFORMATIONAL MACROMOLECULES

The linear sequence of

four kinds of nucleotide
monomers in each is
non-random and
carries genetic
information

This information is
needed to specify the
precise amino acid
sequences of proteins
NUCLEOTIDES
THE CHEMICAL STRUCTURE
RNA and DNA each consist of only
four different types of nucleotides,
the monomeric units

Each nucleotide consists of a five-

carbon sugar to which a phosphate
group and N-containing
(nitrogenous) aromatic base are
attached

Each nitrogenous base is either a

purine or a pyrimidine

The sugar-base portion without the

phosphate group is called a
nucleoside
FOUR TYPES OF NUCLEOTIDES
THE CHEMICAL STRUCTURE & COMMON NOMENCLATURE
DNA VS RNA
BASIC CHEMICAL DIFFERENCES
NUCLEOTIDES IN NUCLEIC ACIDS
ARE JOINED TOGETHER USING PHOSPHODIESTER BONDS
NUCLEOTIDES
FORM LINEAR POLYNUCLEOTIDES THAT HAVE DIRECTIONALITY
Nucleic acids are linear polymers of
nucleotides linked by a 3ʹ,5ʹ
phosphodiester bridge, a phosphate
group linked to two adjacent
nucleotides via two phosphodiester
bonds

The polynucleotide formed by this

process has a directionality with a 5ʹ
phosphate group at one end and a 3ʹ
hydroxyl group at the other

Nucleotide sequences are

conventionally written in the 5ʹ to 3ʹ
direction
NUCLEOTIDES
FORM LINEAR POLYNUCLEOTIDES THAT HAVE DIRECTIONALITY
COMPLEMENTARY BASE PAIRING
FUNDAMENTAL PROPERTY OF NUCLEIC ACIDS

Complementary
base pairing allows A
to form two hydrogen
bonds with T and G to
form three hydrogen
bonds with C

This base pairing is a

fundamental property
of all nucleic acids
STRUCTURE OF DNA
DNA IS A DOUBLE STRANDED ALPHA HELIX
Francis Crick and James Watson
postulated the double helix structure of
DNA in 1953

The structure accounted for the known

physical and chemical properties of DNA

It also suggested a mechanism for DNA

replication

Two antiparallel and complementary

strands of DNA twist around a
common axis to form a right-handed
spiral structure
DNA APLPHA HELIX
IS STABILISED BY WEAK HYDROGEN BONDS
DNA HELIX GROOVES
ALLOW INTERACTIONS WITH PROTEIN COMPLEXES

PROTEIN

DNA HELIX
DNA
MOLECULAR 3D VISUALISATIONS
RNA - RIBONUCLEIC ACID
MASS-PRODUCED DNA TRANSCRIPT
RNA IS NOT JUST FOR DATA TRANSFER
ALSO CATALYSIS, REGULATION AND STRUCTURAL FUNCTIONS
tRNA rRNA
transports amino acids in translation structural element of ribosomes
OTHER ROLES OF NUCLEOTIDES
BEYOND THE GENETIC CODE
ATP - ADENOSINE TRIPHOSPHATE
UNIVERSAL ENERGY CARRYING MOLECULE OF ALL CELLS
PHOSPHATE SUGAR NITROGENOUS BASE
CARBOCHYDRATES
CARBOHYDRATES
STAPLE OF OUR FOOD (ENERGY CARRYING MOLECULES)
 CLASSIFICATION OF CARBOHYDRATES
FROM MONO TO COMPLEX POLYSACCHARIDES
MONOSACCHARIDES DISACCHARIDES OLIGOSACCHARIDES POLYSACCHARIDES
(one sugar monomer) (two sugar monomers) (2-10 sugar monomers) (>10 sugar monomers)

FUNCTIONAL NUMBER OF
GROUP CARBON ATOMS

ALDOSES TRIOSES
KETOSES PENTOSES

EXAMPLES
GLUCOSE SUCROSE RAFFINOSE GLYCOGEN

FRUCTOSE LACTOSE STARCH

GALACTOSE MALTOSE CELLULOSE

MONOSACCHARIDES (SUGARS)
BASIC SUBUNITS OF CARBOHYDRATES

• general chemical formula

(CH2O)n
• two basic chemical
structures: aldoses &
ketoses
• can be formed by
multiple carbon atoms
(e.g. triose, pentose,
hexose etc)
•Easily dissolved in water
MONOSACCHARIDES
USUALLY FORM RING STRUCTURES IN AQUEOUS SOLUTIONS
Chemical equilibrium between the linear and ring structures of
monosaccharides greatly favours the formation of rings.
MONOSACCHARIDES
ENERGY SOURCES FOR CELLS USED IN METABOLIC PATHWAYS
MONOSACCHARIDES’ DERIVATIVES
SUGARS CAN BE MODIFIED WITH FUNCTIONAL GROUPS
DISACCHARIDES
TWO MONOSACCHARIDES JOINED BY A GLYCOSIDIC LINKAGE
glycosidic bond

glycosidic bond
DISACCHARIDES
TWO MONOSACCHARIDES JOINED BY A GLYCOSIDIC LINKAGE
The linkage of disaccharides is a
glycosidic bond, formed between
two monosaccharides by the
elimination of water

Glycosidic bonds involving the α

form of glucose are called α
glycosidic bonds (e.g., maltose);
those involving the β form are
called β glycosidic bonds (e.g.,
lactose)
OLIGOSACCHARIDES
OFTEN USED TO MODIFY PROTEINS AND LIPIDS
GLYCOPROTEINS GLYCOLIPIDS
proteins that contain oligosaccharide lipid molecules bound to
chains (glycans) covalently attached to oligosaccharides, generally present in the
polypeptide side-chains. The lipid bilayer. Additionally, they can serve as
carbohydrate is attached to the protein in receptors for cellular recognition and cell
a post-translational modification. This signalling
process is known as glycosylation.
OLIGOSACCHARIDES
ARE IMPORTANT PART OF THE CELL MEMBRANE
POLYSACCHARIDES
FORMED BY CHAINS OF HUNDREDS OF MONOMER UNITS
STORAGE POLYSACCHARIDES
ARE USED AS ENERGY STORAGE BY PLANTS AND ANIMALS
STARCH
a polysaccharide of glucose
produced by most green plants
as an energy store. It is the most
common carbohydrate in human
diets and is contained in large
amounts in staple foods like
potatoes, wheat.

GLYCOGEN
a multibranched polysaccharide
of glucose that serves as a form
of energy storage in humans,
animals, fungi, and bacteria
STRUCTURAL POLYSACCHARIDES
ARE USED AS STRUCTURAL ELEMENTS BY PLANTS

CELLULOSE
•linear polymer of glucose
• major component of plant
cell walls
•most abundant organic
compound on earth
STRUCTURAL POLYSACCHARIDES
ARE USED AS STRUCTURAL ELEMENTS BY ARTHROPODS

CHITIN
• monomers are modified
amino sugars
•linear, unbranched polymer
of N-Acetyl-D-glucosamine
• major component exoskeleton
in insects and crustaceans
• found in cell walls of fungi
LIPIDS
LIPIDS (FATS)
ARE NOT FORMED BY SIMPLE LINEAR POLYMERIZATION
Lipids are not formed by the same
type of linear polymerization that
forms proteins, nucleic acids, and
polysaccharides

However, they are regarded as

macromolecules because of their
high molecular weight and their
importance in cellular structures,
particularly membranes

They are often defined as water-

insoluble macromolecules
LIPIDS
ARE QUITE DIVERSE
Although heterogeneous, all have a
hydrophobic nature and thus little
affinity for water; they are readily
soluble in nonpolar solvents such as
chloroform or ether

They have relatively few polar groups,

but some are amphipathic, having
polar and nonpolar regions

Functions include energy storage,

membrane structure, or specific
biological functions such as signal
transmission
LIPIDS
ARE QUITE DIVERSE

Due to their diversity lipids can

be divided into six classes based
on their structure
•Fatty acids
•Triacylglycerols
•Phospholipids
•Glycolipids
•Steroids
• Terpines
FATTY ACIDS
ARE FORMED BY LONG HYDROCARBON TAILS
Fatty acids are components
of several other kinds of
lipids

A fatty acid is a long

amphipathic, unbranched
hydrocarbon chain with a
carboxyl group at one end

The polar carboxyl group is

the “head,” and the
nonpolar hydrocarbon
chain is the “tail”
FATTY ACID STRUCTURE
HYDROGEN SATURATION
Saturated fatty acids
each carbon atom in the chain is bonded to
the maximum number of hydrogens. These
have long straight chains that pack
together well

Unsaturated fatty acids

have one or more double bonds, so they
have bends in the chains and are less
tightly packed
TRIACYLGLYCEROLS
FORMED BY GLYCEROL BACKBONE WITH FATTY ACID TAILS
Triacylglycerols, also known as triglycerides, consist of:
Glycerol a three-carbon alcohol with a hydroxyl group on each
carbon
Fatty acids linked to glycerol, one at a time, by ester bonds formed
by the removal of water

GLYCEROL FATTY ACID TAILS

backbone
TRIACYLGLYCEROLS
MAIN FUNCTION IS ENERGY STORAGE
PHOSPHOLIPIDS - AMPHIPATHIC LIPIDS
CRITICAL BUILDING BLOCKS OF CELL MEMBRANES
PHOSPHOLIPID SELF-ASSEMBLY
CAN SPONTANEOUSLY ASSEMBLE INTO LIPID BILAYERS
GLYCOLIPIDS
LIPIDS CONTAINING A CARBOHYDRATE INSTEAD OF A PHOSPHATE
Glycolipids are lipids containing a
carbohydrate instead of a phosphate
group and are often derivatives of
sphingosine and glycerol
(glycosphingolipids)

Carbohydrate groups attached to a

glycolipid may be one to six sugar
units (d-glucose, d-galactose,
or N-acetyl-d-galactosamine)

Glycolipids occur largely on the outer

monolayer of the plasma membrane
GLYCOLIPIDS IN CELL MEMBRANE
ESSENTIAL FOR CELL SIGNALLING AND COMMUNICATION
STEROIDS
DERIVATIVES OF A FOUR-RINGED HYDROCARBON SKELETON
Steroids are derivatives of a four-
ringed hydrocarbon skeleton, which
distinguishes them from other lipids

They are relatively nonpolar and

therefore hydrophobic

Steroids differ from one another in the

positions of double bonds and
functional groups

The most common steroid in animal

cells is cholesterol
STEROIDS
ESSENTIAL AS HORMONES AND IN CELL MEMBRANE
CHOLESTEROL
changes fluidity of the cell membranes
THANK YOU