Download Bacteria - Hagan Bayley

BIOLOGICAL CHEMISTRY
Prof. J.H.P. Bayley, Dr. R.M. Adlington and Dr. L. Smith
Trinity Term 2007 - First Year
Lecture 1
Hagan Bayley
Classification, evolution and diversity of life.
Overview of classification. Evolution of eukaryotes
from bacteria. Development of the nucleus. The
evolution of multicellular organisms. Different
domains of life: bacteria, archaea, eukaryotes, viruses
(different types). [HB]
RECOMMENDED TEXTBOOK
“Biochemistry” 5th edition 2002
JM Berg, JL Tymoczko, L Stryer
Freeman
We call this book “Stryer”
This week mainly Chapters 1 and 2
MOLECULES OF LIFE
WATER
solvent
PROTEINS
NUCLEIC ACIDS
CARBOHYDRATES
LIPIDS
SMALL MOLECULES
METAL IONS
MACROMOLECULES
(POLYMERS)
aggregates
(bilayers, lipoproteins)
WHAT IS LIFE?
Self-replicating, autonomous, evolvable, responsive, intelligent
• Is a virus alive?
Plan, structure, catalysis, energy, generation of variation,
communication, computation … provided by …
Constituents and major roles:
WATER- solvent/ medium
PROTEINS- structural and functional, e.g. catalysts
NUCLEIC ACIDS- code/ plan
CARBOHYDRATES- binding interactions
LIPIDS- encapsulation
SMALL MOLECULES- energy currency, messengers
METAL IONS- energy source, messengers
It is difficult to assign specific roles- Nature is opportunistic
The importance of chemistry in understanding
biology.
Covalent bonds
hundreds of kJ mole-1
Non-covalent bonds
a few to tens of kJ mole-1
Non-covalent bonds
Electrostatic
Hydrogen bonds (also electrostatic)
Van der Waals interactions
Although weak, many non-covalent bonds sum
to yield significant interactions …
e.g.
DNA structure
Protein folding
Binding: enzyme substrates, transmitters
and messengers, protein-protein
interactions etc. etc.
Water
Water is a polar molecule- bent structure
Water has a cohesive (hydrogen-bonded) structure
Weakens non-covalent interactions
Competes for hydrogen bonds
High dielectric (and salt content) weakens electrostatic
interactions
... some important roles of water...
• good solvent: high concentrations of polar molecules, including
salts, can be obtained
• hydrophobic effect - protein folding
• barriers- lipid barriers
??? 0 to 100°C- limits to life... but antifreeze proteins, pressure in
thermal vents
Proteins
Built from 20 amino acids
Amino acids are chiral: ???why ?
L-amino acids, [all are S except cysteine]
Peptide bond formation requires energy, kinetically stable
(t1/2 = 1000 y)
Massive sequence diversity 20n
Sequence is specified in genes
Proteins fold into 3D structures
thus the 1D information of nucleic acids (genes) contains
3D information
Structural
and
functional
versatility
Protein folding and the “hydrophobic effect”
ΔG = ΔH -TΔS
ΔG = -RTlnK
K = exp(- ΔG/RT)
Folding would seem to be entropically disfavored (apparent ordering)
• Folded proteins seem to be more ordered
• Folded proteins are uniform in structure
Water is ordered around hydrophobic molecules
When hydrophobic molecules get together: solvent entropy increases
Hence hydrophobic amino acid side chains become buried
In addition there are numerous non-covalent interactions: electrostatic,
hydrogen bonds, van der Waals etc.
Overall: finally balanced, folded proteins are barely stabletypically -40 kJ mole-1 for a small 100 amino acid protein
Will also meet the hydrophobic effect in lipid bilayer formation …
Hydrophobic effect
Proteins
By virtue of their structural and functional
diversity proteins are:
Structural components
Cytoskeleton
Binding molecules
receptors
antibodies
Catalysts
enzymes
channels, transporters
Motors
Figure
protein
Nucleic acids
DNA- deoxyribonucleic acid
… found in the nuclei of cells …
DNA is also a polymer
Three components
Sugar (deoxyribose)
Phosphate 3’5’ phosphodiesters- rather stable to hydrolysis
nucleobase
Sugar-phosphate backbone
Four different bases GATC
The four nucleic acid bases (DNA, GATC; RNA,GAUC)
Some nomenclature…
Nucleobase (see above) e.g. C, cytosine
Nucleoside- base connected to sugar e.g. deoxycytidine
Nucleotide- phosphorylated derivatives of nucleoside e.g. 5’dCMP
adenosine
ATP
Deoxyguanosine
3’-monophosphate
Nucleic acids
By virtue of their information content:
Encode protein sequences (and structure)
Genes (DNA, some RNA viruses)
mRNA
They also:
Act as adapters- tRNA
Act as catalysts- ribosomal RNA
Regulate gene expression- mi/siRNAs (not in Stryer,
but a hot topic)
What is RNA?- ribonucleic acid
RNA
Ribose v deoxyribose
DNA is more stable than RNA
towards base-catalyzed
hydrolysis ???Why?
Perhaps this is why it now
forms the genome, except in
certain viruses (e.g. influenza)
Conversion is at the level of the
enzyme ribonucleotide reductase
NDP  dNDP
DNA
More stable
RNA world
Proteins
More versatile
Information
flow
Carbohydrates (sugars)
(CH2O)n
Monosaccharides
Carbohydrates (sugars)
Pentoses and hexoses form rings
e.g. glucose
Oligosaccharides- again polymers
Carbohydrates (sugars)
Can be attached to lipids and proteins
Tremendous structural diversity is possible
Carbohydrates
Energy stores, metabolic intermediates
In nucleic acids (ribose and deoxyribose)
Cell walls in bacteria and plants
Attachment to lipid and proteins (recognition by
“lectins”)
Lipids
Example (will return to lipids
and membranes later):
Phosphatidylcholine
Lipids form bilayers, which
encapsulate the cells and
organelles we will be looking
at soon
Small molecules
small molecules in the cell are
often charged with phosphate or
carboxylate groups- therefore,
they cannot pass through the
lipid bilayer
energy generation and
storage- ATP
building blocksUDP-glucose
messengers
Intracellular- cAMP
extracellular e.g.
neurotransmittersacetylcholine
cofactors- vitamin C
ascorbate
etc
Metal ions
Ca2+ as messenger
Metalloenzymes, e.g. Ca, Fe, Cu, Zn
Ion gradients across membranes, e.g. Na+, K+
Exogenous molecules
Poisons, e.g. arsenic
Drugs, e.g. Pt
carboplatin
The elemental composition of cells
Four elements constitute approximately 99% of the
total number of atoms present in the human body
These are
hydrogen
oxygen
carbon
nitrogen
62.8 % (of atoms)
25.4 %
9.4 %
1.4 %
This largely reflects the high content of water in cells
Another seven elements represent approximately 0.9 % of the total number of
atoms in the human body: Na, K, Ca, Mg, P, S and Cl
Additional metal and non-metals are required by some biological systems, but not
by others:
The elemental composition of cells is said to be related to the
composition of seawater:
??? What do you think?
Classification, evolution and diversity of life
Overview of classification. Evolution of eukaryotes
from bacteria. Development of the nucleus. The
evolution of multicellular organisms. Different
domains of life: bacteria, archaea, eukaryotes,
viruses (different types).
In fact, from the biochemical viewpoint, it is
striking how similar are all life forms.
Classification, evolution and diversity of life
Initially, life was classified as either ANIMAL or PLANT
However, as new forms of life were discovered, new
categories – KINGDOMS – were defined.
There were 5 in total –
ANIMALIA, PLANTAE, FUNGI, PROTISTA- Eukaryotes
BACTERIA- Prokaryotes
With new insight into molecular biology (rRNA sequences
especially), three DOMAINS of life have been proposed (Carl
Woese, 1976):
EUKARYA (eukaryotes)
Protists, Fungi, Animalia, and Plantae
BACTERIA (eubacteria, true bacteria)
ARCHAEA
4.5 billion years: recognizable ancestors of bacteria 3.5 billion years ago
Eukaryote: a cell or organism composed of
cells that have a membrane-bound nucleus
and organelles (e.g. mitochondria,
chloroplasts) and genetic material organized
in chromosomes in which the DNA is
combined with histone proteins.
Prokaryotic cells contain no nucleus.
Prokaryotic cells contain no true membrane
bound organelles (e.g. mitochondria).
The Bacteria possess the following
characteristics:
0. B a cteria are prokaryotic cells .
0. Like the Eukarya, they have membranes
composed of unbranched fatty acid
chains attached to glycerol by ester
linkages
0. The cell walls of Bacteria, unlike the Archaea
and the Eukarya, contain peptidoglycan .
0. B a cteria are sensitive to traditional
antibacterial antibiotics but are resistant to
most antibiotics that affect Eukarya.
0. B a cteria contain rRNA that is unique to the
Bacteria as indicated by the presence
molecular regions distinctly different from
the rRNA of Archaea and Eukarya.
0.
Bacteria include mycoplasmas, cyanobacteria,
Gram-positive bacteria, and Gram-negative
bacteria.
The Archaea possess the following
characteristics:
0. Archaea are prokaryotic cells .
0. Unlike the Bacteria and the Eukarya, the
Archaea have membranes composed of
branched hydrocarbon chains attached
to glycerol by ether linkages.
0. The cell walls of Archaea contain no
peptidoglycan .
0. Archaea are not sensitive to some antibiotics
that affect the Bacteria, but are sensitive to
some antibiotics that affect the Eukarya.
0. Archaea contain rRNA that is unique to the
Archaea as indicated by the presence
molecular regions distinctly different from
the rRNA of Bacteria and Eukarya.
0.
Archaea often live in extreme environments and
include methanogens, extreme halophiles, and
hyperthermophiles (record 113°C), acidophiles
(some at pH 1!)
The Eukarya (also spelled Eucarya) possess
the following characteristics:
0. E u karya have eukaryotic cells .
0. Like the Bacteria, they have membranes
composed of unbranched fatty acid
chains attached to glycerol by ester
linkages.
0. Not all Eukarya possess cells with a cell wall,
but for those Eukarya having a cell wall,
that wall contains no peptidoglycan .
0. E u karya are resistant to traditional
antibacterial antibiotics but are sensitive to
antibiotics that affect eukaryotic cells.
0. E u karya contain rRNA that is unique to the
Eukarya as indicated by the presence
molecular regions distinctly different from
the rRNA of Archaea and Bacteria.
The Eukarya are subdivided into the following kingdoms:
a. Protista Kingdom Protista are simple, predominately
unicellular eukaryotic organisms. Examples includes slime
molds, euglenoids, algae, and protozoans.
b. Fungi Kingdom Fungi are unicellular or multicellular
organisms with eukaryotic cell types. The cells have cell
walls but are not organized into tissues. They do not carry
out photosynthesis and obtain nutrients through absorption.
Examples include sac fungi (e.g. Morel), club fungi (e.g.
common mushrooms), yeasts, and molds.
c. Plantae Kingdom Plants are multicellular organisms
composed of eukaryotic cells. The cells are organized into
tissues and have cell walls. They obtain nutrients by
photosynthesis and absorption. Examples include mosses,
ferns, conifers, and flowering plants.
d. Animalia Kingdom Animals are multicellular organisms
composed of eukaryotic cells. The cells are organized into
tissues and lack cell walls. They do not carry out
photosynthesis and obtain nutrients primarily by ingestion.
Examples include sponges, worms, insects, and
vertebrates.
The major organelles of a eukaryotic cell
are:
NUCLEUS – contains the chromosomes, which consist of DNA
and histones. Gene replication. mRNA synthesis. Ribosome
production.
MITOCHONDRIA – principal function is the production of ATP
ENDOPLASMIC RETICULUM:
ROUGH – studded with ribosomes- sites of protein synthesis for
membrane and secreted proteins
SMOOTH –steroid hormone biosynthesis, Ca2+ storage
LYSOSOMES - contain hydrolytic enzymes
PEROXISOMES - contain oxidative enzymes
The lysosomes and peroxisomes degrade foreign substances that
have been brought into the cell (simplification)
GOLGI COMPLEXES –newly biosynthesised proteins are
processed here (post-translational modification), e.g. glycosylated
Plant cells: plastids (e.g. chloroplastphotosynthesis), vacuoles (control hydrostatic
pressure through fluid uptake, storage and
breakdown of molecules), cell wall
Origin of organelles
Membrane invaginations followed by
specialization: nucleus, endoplasmic
reticulum, Golgi etc.
Endosymbiosis: mitochondria,
chloroplasts- ~1 billion years ago
Evidence: inner membrane contains
similar enzymes and transport
systems; contain their own DNA (no
histones), related to that found in
bacteria; ribosomes have similar
biochemical characteristics to those in
bacteria, rRNA sequence similarities
VIRUSES
Viruses are packets of infectious nucleic acids (DNA or RNA)
surrounded by protective protein coats. They are unable to
generate metabolic energy or synthesise proteins
Diseases caused by viruses include the common cold, measles,
smallpox, polio and AIDS
Viruses have genes and show inheritance, but are reliant on host
cells to produce new generations of viruses. Because viruses are
dependent on host cells for their replication they are generally not
classified as "living". Whether they are "alive", they are obligate
parasites, and have no form which can reproduce independently of
their host. Like most parasites, they have a specific host range,
sometimes specific to one species (or even limited cell types of one
species) and sometimes more general.
PRIONS
A prion is an infectious agent made only of protein. Prions are
abnormally-structured forms (amyloid) of a host protein, which are
able to convert normal molecules of the protein into the abnormal
structure. Prions cause diseases such as BSE (mad cow disease).
Lambda bacteriophage:
The viral DNA molecule is
contained within an icosahedral
protein coat to form the head
The DNA is injected into the
bacterial host through the tail
The tips of the tail fibers bind to
specific sites on the outer membrane
of the host
Influenza
Negative strand RNA virus
Eight separate genes
8 min/ frame
Total time 12 h
1.4 mm field
Multicellular organisms
Differentiation and specialization
differentiated cells are genetically identical but have different properties
because of differential gene expression
Cell communication
Primitive example: slime mold Dictyostelium (not really a mold)
Exist as single cells in a nutrient rich environment
Form aggregrates when starved (signal is extracellular cAMP);
cAMP binds to extracellular receptors, triggers release of more cAMP and
movement to higher cAMP concentrations, promotes aggregration
Formation of fruiting body that can be carried by the wind.
A human contains about 1014 cells
begins as a single cell
regulated gene expression
cell division
cell migration
programmed cell death (apoptosis)
responses to neighboring and distant cells
Caenorhabditis elegans- nematode worm
completely programmed 959 cells
The biochemistry underlying all
organisms has a common origin and
was largely fixed early in evolution.
Important processes usual exist and can
be studied in lower organisms.