SCIE1106

Macromolecules 2

Suggested Reading:

➢ Essential Cell Biology, Alberts et al.

(4ed), Chapter 2, pages 46-50, 55-5862-
64, 74-79

At a minimum:
Read the parts corresponding to
the lecture material!

by
Dr. Martha Ludwig
Modified , revised (2022) and presented by
Diagrammatic representation of the various macromolecules
in the cell cytoplasm Dr Thomas Martin
 Learning outcomes
You will be able to:

• describe the building blocks, composition, structure, formation and breakdown of

nucleic acids
• remember the biological roles of nucleotides and their derivatives
• describe the building blocks, composition, structure, formation and breakdown of
proteins
• remember types of noncovalent interactions and that they impact on stability and
interaction of macromolecules
• describe the origin of non-covalent forces
Macromolecules - DNA and RNA
 The Central Dogma
Nucleic Acids & Proteins

➢ DNA transcribed into RNA which

is translated into protein

More in topic 2 lectures on

DNA to Proteins: the Central
Dogma

Alberts et al. (10) Essential Cell Biology, Fig 1-2

 Nucleic Acids

➢ Deoxyribonucleic acid (DNA)

and
➢ Ribonucleic acid (RNA)

➢ information storage and retrieval

▪ RNA - transient carrier of
information
▪ DNA - long-term storage of
hereditary material

➢ composed of nucleotides
▪ nitrogenous base
▪ five carbon sugar (pentose)
▪ phosphate group

Alberts et al. (04) Essential Cell Biology, Panel 2-6

 Nucleotides contain Nitrogenous Bases

Alberts et al. (04) Essential Cell Biology, Panel 2-6

➢ Contain nitrogen (N)

➢ Pyrimidines (single ring structure): cytosine (C), thymine (T) and uracil (U)
➢ Purines (double ring structure): adenine(A) and guanine (G)
➢ DNA contains A, C, G, and T
➢ RNA contains A, C, G, and U
➢ Note numbering to distinguish carbons and
nitrogens in bases
 Nucleotides contain Pentose sugars

Alberts et al. (04) Essential Cell Biology, Panel 2-6

➢ Note numbering to distinguish carbons in sugars has a prime (’) behind the number to
distinguish the numbering from the numbering of carbons in a nitrogenous base

➢ RNA contains ribose

➢ DNA contains 2’-deoxyribose: hydroxyl group (-OH) on 2' carbon is replaced by a
hydrogen ➔ this makes DNA a lot more stable than RNA against chemicals
➢ Nitrogenous base + pentose = nucleoside, e.g. adenosine
 Nucleotides contain Phosphate Groups

➢ Phosphoanhydride bonds
➢ connect
phosphate groups
➔ minus water = anhydrid
Condensation reaction = release of water

DNA & RNA are negatively charged

• In DNA (RNA), the phosphates are normally joined to the C5 hydroxyl group of the
deoxyribose (ribose) sugar.
• Mono-, di- and triphosphates are common

Adenosine Adenosine Adenosine

monophosphate diphosphate triphosphate

Figures from: http://www.ncbi.nlm.nih.gov/books/NBK21737/, Alberts et al. (04) Essential Cell Biology, Panel 2-6
 Nucleotides differ in DNA and RNA

• DNA had 2-desoxyribose

• RNA has ribose

• DNA has thymine as a base in addition to guanine, adenine and

cytosine
• RNA has uracil as a base in addition to guanine, adenine and cytosine

• DNA has 2-desoxyribonucleotides: dATP, dCTP, dGTP and dTTP

• RNA has ribonucleotide: ATP,CTP, GTP and UTP
 Nucleic Acids -
Linear Polymers of Nucleotides

➢ Nucleotides are joined together through

condensation reactions (water released)
➢ Breaking the bond requires water:
hydrolysis
➢ Phosphodiester bonds link adjacent
nucleotides in nucleic acids
➢ hydroxyl group on 3' carbon of pentose
covalently linked to phosphate group attached
to 5' carbon of adjacent pentose

sugar phosphate backbone

Alberts et al. (04) Essential Cell Biology, Panel 2-6

 Nucleic Acids -
Sequence and Directionality

➢ polymers (or strands) have directionality

a 5' end and a 3' end

➢ by convention the sequence of bases (the

genetic information) in a nucleic acid strand
is read 5' to 3', using the single letter code

•5'-G-A-T-C-3'

➢ in cells
▪ RNA is usually single stranded
▪ DNA is nearly always double
stranded

Alberts et al. (10) Essential Cell Biology, Fig 2-25

 Nucleic Acids - DNA Double Helix

➢ two DNA strands are anti-parallel

➢ sugar-phosphate backbone on the
outside, bases projecting inward
➢ strands are held together by
hydrogen bonds between bases

▪ G pairs with C (3 H-bonds)

▪ A pairs with T (2 H-bonds)

➢ strands are complementary

➢ The ratio of purines to pyrimidines
is 1:1

Alberts et al. (10) Essential Cell Biology, Fig 5-2

 Nucleotides - Other Functions

Carriers of chemical energy

➢ Phosphoanhydride bond can

be hydrolysed ➔ e.g ATP
➢ high energy conserved in
this bond
➢ cleavage releases energy ➔
used by prokaryotic and
eukaryotic cells

Signalling molecules Combined with other groups

as Coenzymes
➢ activate enzymes
& turn on genes

e.g. cyclic AMP

➢ when activated, transfer groups
(cAMP)
between molecules (acetyl
CoA)
Alberts et al. (04) Essential Cell Biology, Fig 2-24; Panel 2-6
Macromolecules - Proteins
 Amino acids are building blocks of proteins

amino acids
➢ building blocks of proteins
➢ Amino acids have:
▪ An alpha carbon
▪ carboxylic acid group
▪ amino group
▪ side chain (R group)
gives distinctive property
of individual amino acids
➢ when free in solution,
carboxylic acid, amino and The carboxylic acid, amino and side chain
some side chain groups are groups are all covalently attached to same
ionised at pH 7 (inside cell) carbon atom, the -carbon
Same 20 amino acids found
in proteins of bacteria,
animals and plants More in topic 3: Proteins &
Recombinant DNA Technology
Figure from: Alberts et al. (10) Essential Cell Biology, Fig 2-21
 Proteins are Linear Polymers of Amino Acids

Peptide bonds

➢ link amino acids

➢ carboxylic acid group of one amino

acid reacts with amino group of a
second amino acid

➢ condensation reaction = water

removed
➢ Breaking the bond requires
water: hydrolysis

Note: Each amino acids, even in the

peptide chain, still has an amino
group and a carboxylic acid group

Alberts et al. (10) Essential Cell Biology, Fig 4-1

 Proteins
- Linear Polymers with directionality

➢ polymers have directionality:

▪ amino (N-) terminus &
▪ carboxyl (C-) terminus
➢ by convention an amino acid
sequence is read from the N-
terminus to the C-terminus
▪ three-letter abbreviations -
Phe-Ser-Glu-Lys
▪ single-letter abbreviations -
FSEK

Alberts et al. (10) Essential Cell Biology, Fig 2-22

 Macromolecules - Some Common Themes

Condensation reactions form:

▪ polysaccharides from simple sugars
▪ proteins from amino acids
▪ nucleic acids from nucleotides

Figure from: Alberts et al. (10) Essential Cell Biology, Fig 2-33
Noncovalent Interactions
 (Macro)molecules interact via Noncovalent
Interactions

➢ Ionic interactions
➢ Hydrogen bonds Hydrophobic
➢ Hydrophobic forces interactions
➢ Van der Waals attractions
Hydrogen
Individually: bonds
• Most are weak interactions
Many together:
• tight binding Ionic
interactions
Biological relevance:
▪ Mediates molecular interactions
▪ Stabilise macromolecule
structures http://www.uic.edu/classes/bios/bios100/summer2002/lect
02.htm
Noncovalent Interactions - Ionic Interactions

Alberts et al. (10) Essential Cell Biology, Fig 2-8

➢ electrons lost or gained by atoms ➔ electrically charged (ions):

▪ positive charge (lost electron) ➔ cation (e.g. Na+)
▪ negative charge (gained electron) ➔ anion (e.g. Cl-)

➢ opposite charges attract each other and hold together by an ionic bond
▪ In absence of water - very strong (e.g. NaCl)
▪ In presence of water - weak (charges shielded by water)
 Polar Covalent Bonds

polar covalent bond ➢ Unequal sharing of electrons belonging to a bond

in water: H2O between two atoms
➢ Caused if one atom in a bond has a higher affinity =
electronegativity to electrons than the other atom(s)
➢ Example:
a) Oxygen in water attracts electrons more strongly than
hydrogen
b) Oxygen in methanol attracts electrons more strongly
than hydrogen and more strongly than carbon

polar covalent bond

in methanol
Alberts et al. (10) Essential Cell
Biology, Fig 2-12
http://chemwiki.ucdavis.edu/Organic_Chemistry/
Alcohols/Properties_of_Alcohols
Noncovalent Interactions - Hydrogen ‘Bonds’

➢ Polar covalent bonds create a polarized

molecule (Dipole) which can attract
other polarized molecules
➢ Hydrogen bonds form if the polarized
molecule contains a hydrogen atom AND
this hydrogen atom is between two
electron attracting atoms (in water for
example these are oxygen but it can also
Alberts et al. (10) Essential Cell Biology, Panel 2-2 be nitrogen in other molecules)
http://staff.jccc.ne
t/pdecell/chemistr
➢ Hydrogen bonds are based on
y/bonds.html#hyd electrostatic interactions and not as
robond
covalent bonds on the sharing of
electrons
➢ 1/20th as strong as a covalent bond
➢ Strongest when the three atoms are in a
straight line
 Noncovalent Interactions - Hydrophobic Forces

Adding oil (hydrophob) to water makes the

drops combine to form a larger drop because
water molecules are attracted to each other
squeezing the oil drops together to form a
larger drop Hydrophobic (water-hating)
molecules cluster together to
http://staff.jccc.net/pdecell/chemistry/hydrophob.html
http://academic.brooklyn.cuny.edu/biology/bio4fv/page/hydropho.htm exclude water molecules

Example: oil droplets in water

 Noncovalent Interactions - van der Waals
Attractions

From: https://www.zmescience.com/science/physics/direct-
measurement-of-van-der-waals-force-made-for-the-first-time/

➢ Van der Waals forces include attraction and repulsions between atoms,
molecules, and surfaces, as well as other intermolecular forces
➢ Result from a transient shift in electron density around a nucleus that creates a
transient charge to which a nearby atom can be attracted or repelled.
➢ Weak interactions
➢ Effective when atoms have a specific distance from each other

Alberts et al. (10) Essential Cell Biology, Panel 2-7; Alberts et al. (08) Molecular Biology of the Cell, Fig 2-11;
http://animals.timduru.org/dirlist/gecko/A4_181-Gecko.jpg
 Noncovalent Interactions
- Geckos use van der Waals Attractions

Edited from ‘Smart materials (1 of 5): Gecko Adhesive fit for Spiderman’ http://www.youtube.com/watch?v=gzm7yD-JuyM