The macromolecules of life

Insight into the origin of life of Earth

Cosmos, by Carl Sagan, Part 2 – One Voice in the Cosmic Fugue

Cosmic calendar – start of time = Jan 1st, now (~14 billion years later) = Dec 31st
 BMS1021 Biochemistry

The Chemical Composition of Cells - 3

Water Proteins Carbohydrates Lipids Nucleic Acids

Dr. Jérôme Le Nours

Group Leader
Jerome.lenours@monash.edu

Comparative Immunology Laboratory

Department of Biochemistry and Molecular Biology
Biomedicine Discovery Institute
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 What makes you …YOU?

• Almost every cell in your body has a copy of your DNA

• Your DNA has ~3 billion ‘bits’ of information
• or 101800000000 potential combinations (1080 atom in the universe)
• You are unique

• Your cells have the same fundamental building blocks as every other life-
form we know …including amino acids, nucleotides, sugars, lipids
elements

• 99.9% of your DNA sequence is the same as the person sitting next to you
• 96% similar to Chimpanzees
• 63% similar genes in sea-sponges
 What makes you YOU?
Life forms are related – separated by time
www.evogeneao.com/explore/tree-of-life-explorer

~700 million year common ancestor to humans and sponges (your extended family tree)

• Our DNA defines who and what we are

• Our DNA reveals our origin

What is DNA?
 Learning objectives

• the structure of nucleic acids

• the structure of lipids
• the major functions of each type of molecule
• the basic structure of cellular membranes
 Resources
Biology – Campbell
11th edn. Chapter 5 pp. 72-75, 84-89
Chapter 7 pp. 124-129

Principles of Biochemistry – Lehninger

7th edn. (2017) Chapter 8 pp. 279-317
Chapter 10 pp. 361-386

Lectures in BMS1011 on Lipids also cover this topic in more detail

Cosmos: A Personal Voyage (1980) by Carl Sagan

Cosmos: A Spacetime Odyssey (2014)
 DNA is a polymer of nucleotides

(DNA - deoxyribonucleic acid)

(RNA - ribonucleic acid)

• Extremely long molecules

• Human chromosome #6 is 170 million nucleotides

in length (~5% of genome) 1 nucleotide

• ~ 5 cm in length if stretched out

 Nucleic acids
• Nucleic acids (DNA and RNA) are polymers of nucleotides
• Nucleotides are made of three components

3
2 - A sugar
2

Uridine monophosphate (UMP)

1 - A nitrogenous base
U, T, C (pyrimidines)
A, G (purines) 3 - A phosphate
group
‘U’ replaces ‘T’ in RNA
DNA is made up of deoxyribonucleotides

Deoxyadenosine Deoxyguanosine Deoxythymidine Deoxycytidine

monophosphate monophosphate monophosphate monophosphate

dAMP dGMP dTMP dCMP

dA dG dT dC

A G T C
RNA has ribonucleotides (not deoxy ribonucleotides)
 Phosphodiester bonds link nucleotides

Thymidine
5’ (T)
C5 Condensation reaction
DNA polymerase
C3

Adenosine
By convention DNA is written
(A) from 5’ to 3’
C5
This DNA sequence is T A A
Sugar-phosphate (and not A A T)
C3
DNA backbone
Adenosine
(A)
C5 Your DNA has ~3 billion letters
arranged and joined perfectly
C3

3’
 DNA comprises two complementary strands
One strand is referred to as the
sense strand and the other the
anti-sense or complementary
strand.

Adenosine Thymidine • A -T
• T-A
• C-G
• G-C

The anti-sense strand is a

reverse complement to the sense
strand.

Guanosine Cytidine The two strands run in antiparallel

Two copies of genetic information

A base pair (bp) Sense Anti-sense
 DNA forms a double helix structure
• Two chains bound by
hydrogen bonds

• Bases are relatively

hydrophobic and ‘stack’
causing the strand to wind

• Minor groove and major

groove

DNA helix

• DNA is tightly coiled into the

cell by histone proteins

• For example 5 cm down to

10 µm in length (5000 fold
reduction)
 DNA replication
• Specific enzymes
replicate the DNA
before cell division

• High fidelity process

- errors are NOT
passed on to
daughter cells

• DNA has the

information to make
a copy
 Why do we have DNA?
• DNA encodes all the genes
within an organism*

• Genes are transcribed

producing mRNA (messenger
RNA)

• mRNA is translated into protein

* Some organisms (e.g. certain viruses) have an RNA based genome instead of DNA
 Lipids: a diverse group of hydrophobic molecules
Fatty acids and their derivatives are insoluble in water

Fats, such as triacylglycerols and

waxes, are used as energy stores

Phospholipids, found in
membranes, are used as
structural molecules

Other lipids, such as steroids, act

as signals, co-factors(Vitamins E,
K) and pigments (carotene,
chlorophyll)
 Fatty acids have hydrophobic ‘tails’
Can be 4 - 36 carbons in length. Always an even number

• Palmitic acid C16 • Oleic acid C18

• fully saturated chain • unsaturated chain
• no double bonds • one double bond

Palmitic acid Oleic Acid

 Storage of energy -Triacylglycerols

• Glycerol is linked by an ester bond

to three fatty acids

• Also known as triglycerides

Triacylglycerol
 Storage of Energy - Triacylglycerols
• Saturated fats are fully
hydrogenated. They have no
double bonds in carbon backbone

• Unsaturated fats have one or more

double bonds in carbon backbone,
resulting in a bend in fatty acid ‘tail’

Close packing of molecules Close packing is hindered

(typically stored in mammals) (typically stored in plants)
 Storage of Energy -Triacylglycerols

Guinea pig adipocytes filled with stored triacylglycerol

Insulating
Buoyant
 Structural Lipids - Phospholipids
Phospholipids are composed of a glycerol molecule linked to
two fatty acid molecules and a phosphate group.

Amphipathic

• Hydrophilic phosphate head

• Hydrophobic fatty acid tail

 Membranes are made of phospholipids

• Phospholipids are arranged into a bilayer

• Hydrophobic tails shielded from water

• Hydrophilic heads exposed to water

• Major component: Phosphatidylcholine

Water

Water
 Membranes are fluid structures
• Phospholipid molecules are not
covalently linked together in the
membrane

• Lipid molecules are in constant Lateral movement

lateral motion (~107 times per second)

Flip-flop
• Unsaturated phospholipids enhance Viscous (~ once a month)
membrane fluidity

• Saturated phospholipids are closely

packed and less fluid

• The ratio of Saturated : Unsaturated

lipid determines membrane fluidity,
and can change with an organism’s
environment. Fluid
 Membranes and their role in cellular function
Cells are surrounded by a membrane

• Keeps molecules inside the cell and controls entry to the cell

• Prokaryotes (bacteria and archaea) and eukaryotes have cell

membranes (plasma membranes).

• Eukaryotes have extensive internal membrane structures

2µm 10µm
Electron micrograph of mammalian cell
Bacteria Red Blood Cells
showing internal membranes
Fluid Mosaic Model of the Cell Membrane
 Lipids as signals, cofactors and pigments
Lipids have active roles in the cell
• Signalling – steroid hormones or intracellular messengers

Testosterone PIP2

• Co-factors in electron transfer reactions

Co-enzyme Q10

• Light capturing pigments in vision and photosynthesis

Chlorophyll a

Many of these are made from cholesterol, plasma membrane phospholipids or fat-
soluble vitamins A, D, E and K
 Steroid hormones
• Cholesterol is the main precursor for steroid production

• Carbon skeleton of 4 fused rings

 Fat soluble vitamins
• Humans are unable to synthesise
vitamins
• Small amounts of vitamin A, D, E
and K are needed to maintain
health
• The body stores them in the liver
and adipose (fat) tissue
• Most people do not need vitamin
supplements
• Excess vitamin A, D, E or K can
be toxic leading to health
problems
• Fat-soluble vitamins aren't lost
when the foods that contain
them are cooked.
Vitamin A
Vitamin E
Rickets - vitamin D deficiency
 Fat soluble vitamins - Vitamin D

• Cholesterol is a precursor to vitamin D produced in the body

• Sunlight is required to turn cholesterol into vitamin D

• 30 mins exposure (UV-B) → 20,000 IU (500 µg). Requirement 4 - 600 IU /day
• avoidance will undermine our ability to synthesize vitamin D

• Vitamin D-rich foods are also rich in cholesterol, so low-cholesterol (low fat) diets are inherently deficient
in vitamin D. Cod liver oil is best source. Plant foods do not contain vitamin D.
 The macromolecules of life
A wonderful complex synergy of these molecules enable life

The ‘simple’ Escherichia coli cell

 Summary

• Nucleic acids are polymers of nucleotides

• DNA makes up the genetic material of the
cell (some bacteria use RNA instead)
• RNA is involved in protein production

• Lipids are hydrophobic in nature

• Triacylglycerols are used to store energy
• Phospholipids form bilayer membranes
• Membranes perform vital functions in cells
• Steroids and vitamins are ring structure lipids

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