Theme 1:Introduction to Molecular and Cellular Biology Flashcards
What is biochemistry?
Biochemistry is the branch of science concerned with the chemical and physio-chemical processes and substances which occur within living organisms
What is studied in biochemistry?
Biochemistry is the study of chemical components of the body
It studied chemical reactions that govern living processes.
what did Feng Zhang do?
Zhang pioneered the development of CRISPR-cas9 as a genome editing tool and its use in eukaryotic cells
What is CRISPR?
CRISPR is a genetic system that conveys immunity to virus infection in bacteria.
Gives access to every single geno
It is a revolutionary experimental tool
What components are used as a molecular scalpel to cut DNA at a specific site?
- a guide RNA
- a CRISPR-associated endonuclease(Cas protien)
Cas9 RNA programmable endonuclease
what do Engineered CRISPR systems do?
Engineered CRISPR systems cut DNA at a specific site to edit a genome which can convey immunity to a virus infection in bacteria
What ethical problems arise with CRISPR in the clinic?
A chinese scientist used CRISPR to make the first genetically edited babies.He claims to have disabled a gene called CCR5, which encodes a protein that allows HIV to enter cells.But He might have inadvertently caused mutations in other parts of the genome, which could have unpredictable health consequences
What is CAR T-cell therapy?
Chimeric antigen receptor (CAR) T-cell therapy is a way to get immune cells called T cells (a type of white blood cell) to fight cancer by changing them in the lab so they can find and destroy cancer cells
What are T-cells?
T-cells are specialised white blood cells of the immune system
T cells are engineered to express CARs that recognise cancer cells
How does CAR T-cell therapy work?
T-cells are specialised white blood cells of the immune system
They are isolated from a patient and a custom designed gene is introduced into the cells.
Cells containing the gene are grown in culture to prepare an inoculum
CAR T-cells are infused back into the patient
T-cells target cancer cells for killing
Is there any evidence of CAR T-cell therapy working?
yes- young girl (emily whitehead) went into remission and was giving low rate to survive. recieved cells age 7 and is now age 16.
How has biochemistry informed
our understanding of the virus and
our approach to managing it?
RNA sequence - determines the
functional genes of the virus
- Origin of the virus
- Possible drug targets
- Possible vaccine candidates
What is key to understanding how to target VIRUSES with drugs?
knowing how it mutates is key to understanding how to target with drugs?
Typically what do vaccines contain?
Typically vaccines contain either killed virus or a
protein fragment of the virus
What are antibodies?
Antibodies are specialized, Y-shaped proteins that bind like a lock-and-key to the body’s foreign invaders
How can antibodies work?
by binding to a viral protein and
preventing its function
What is leading to a potential arms race with the virus?
Some variants are less susceptible to monoclonal
antibodies
How does biochemistry underpin advances in life sciences and biotechnologies.
By providing a description of the chemical
components and mechanisms of living
cells,
How is monoclonal antibodies used today?
Currently over 75 monoclonal antibodies are approved
for a variety of conditions ranging from cancer to
autoimmune diseases to haemophilia and macular
degeneration
How is biochemistry involved in creating monocolonal antibodies?
Creating monoclonal antibodies involves
biochemistry at every level -
- Generating antibodies by immunisation
- Characterizing antibody reactivity
• Creating
monoclonal antibodies -
molecular cell biology
• Humanizing antibodies - adapting from
other species
• Purifying antibodies - for use in
patients
What are the main elements that compose the human body (and their %)
Oxygen (65%) carbon(18%) hydrogen(10%) Nitrogen (3%) Others (less than 1%)
What are some of the other eements that make up cless than 1% of the human body?
Calcium phosphorus sulfur sodium chlorine magnesium
structure
and functional groups in Carbon
tetravalent,
tetrahedral
geometry,
the backbone of
biomolecules,
low electronegativity
structure
and functional groups in Oxygen
- divalent,
highly
electronegative
structure
and functional groups in Nitrogen
trivalent,
somewhat
electronegative
structure
and functional groups in Hydrogen
monovalent,
least
electronegative
structure
and functional groups in phosporus
pentavalent,
low
electronegativity –
labile bonds
structure
and functional groups in Sulphur
divalent,
moderate
electronegativity; redox
What is Chemical bonding driven by?
•Chemical bonding is driven by the
outermost electrons of atoms
What occurs in covalent bonding?
In covalent bonding, atoms
share electrons to form
molecular orbitals that comprise
electron pairs.
What are molecular orbitas?
In chemistry, a molecular orbital is a mathematical function describing the location and wave-like behavior of an electron in a molecule. … When multiple atoms combine chemically into a molecule, the electrons’ locations are determined by the molecule as a whole, so the atomic orbitals combine to form molecular orbitals.
What is – stereochemistry
Stereochemistry is the study of the three‐dimensional structure of molecules
what are molecules specific shape based on?
Molecules adopt specific shape – stereochemistry – based on their bond systems, a key to molecular structure
when are ions formed?
•Ions are formed when
atoms lose or gain electrons
and acquire FIXED
CHARGE
what are ionic bonds?
•Ion pair interactions
•Ionized groups such as acids
and bases can form ionic
bonds
are ionic compund soluable or insoluable in water ?
•Ionic compounds are
soluble in water due to
solvent polarity
What is poarity?
In chemistry, polarity is a separation of electric charge leading to a molecule or its chemical groups having an electric dipole moment, with a negatively charged end and a positively charged end.
What is polar?
•Polar is the term for bonds
and compounds with
asymmetric charge distribution
What is electronegatiity?
“relative strength of
attraction of atomic nucleus for electrons”
What does asymmetry in e- lead to within a molecule?
Asymmetry in e- distrubution leads to
asymmetry in charge within a molecule
what is dipole?
A bond or molecule whose ends have opposite charges.
structured
distribution of charge in space.
How can covalent bonds have ‘partial ionic charcter?
• Atoms have different tendencies to attract electrons: ‘electronegativity’
• asymmetric sharing of electrons in a
covalent bond
• AND THUS, a partial charge across
the bond, or dipole
Many important bonds in
biochemistry are noncovalent. name some of these bonds.
•Van der Waals interactions •Hydrogen bonds •Ion-dipole interactions •Ionic bonds – paired charge interactions
What are noncovalent bonds?
a relatively weak bond formed between molecules without sharing electrons
what energy do chemical bonds have ?
•Energy of formation and
dissociation
name 3 features of van der waals interactions
•A proximity effect, the induced
dipole
- Very short range
- Molecular packing
what is an example of van der waal interactions?
•Design of gecko feet has inspired
dynamically adhesive “van der Waals
materials”
•biomimetic design
•COOPERATIVITY
– many small
bonds add up to great energy
Name four features of hydrogen bonds
•Dipole interactions involving a
shared proton = H atom •Polar interaction •H2O can form H-bonds •A great deal of biomolecular
structure is driven by H
-bonding
What are charged- based interactions?
•Electrostatic interactions take place between charged groups and a) other charged groups b) dipoles
•Can be highly influenced by
solvent and other environmental
effects
What are iconic bonds?
ionic bonds involve complete transfer of electrons between
donor and acceptor atoms
e.g. NaCl = Na+ : Cl
How do ions interact?
ions have fixed electrical charges and interact by complementary attraction (coulombic forces) – like magnets
How do charged groups have a profound influence on the structure of water?
charged groups have a profound influence on the structure of
water, by organizing it through charge:dipole interactions.
What are hydrophobic bonds?
– van der Waal’s interactions
in polar solvent: increased energy due to
“repulsion” by solvent
Properties of water (6)
Solvent
Highly polar molecule
Interacts with charged moities as
well as polar groups in molecules
Self-interacts to form hydrogen
bond network in bulk water
Disruption of the H-bond network
and ordering of water around
hydrophobic surfaces leads to
hydrophobic bonding potential
Strong entropic effect due to
changes in ordering of water
molecules
what is bioenergetics?
Bioenergetics is the branch of biochemistry that focuses on how cells transform energy, often by producing, storing or consuming adenosine triphosphate (ATP).
what does biological organisation require?
Biological organisation requires the flow of energy
in the concept of bioenergetics where is energy stored and how is it moved?
Energy is stored in covalent bonds and
moved through high energy compounds
What is the primary source of biological energy?
solar radiation
how does solar radiation work?
– Photosynthesis
– light mobilizes electrons in chlorophyll
– electrons provide reducing power
= electrochemical energy
– Energy is stored by synthesis of organic
molecules – carbohydrates
– Chloroplasts accomplish this in plants
– Mitochondria coordinate energy metabolism
in animal and plant cells
what is ATP?
adenosine
triphosphate
Is a major carrier of chemical
energy.
Free energy of
hydrolysis of terminal
phosphate donates energy to
biochemical reactions.
what is the role of covalent bonds in DNA
• establish the structure of the
nucleotide bases
• their linkage to the sugars
• the continuous phosphodiester
backbone
what is the role of hydrogen bonds in DNA
• establish the linkage between complementary bases that defines the double strands and template character of DNA and RNA
what is the role of van der waals interactions in DNA
• lead to base stacking that
stabilizes the double helix
What is the role of charge interactions in DNA
between the phosphate groups
of the backbone and water and
with proteins …
what is the primary function of DNA
: its primary function is the
storage and replication of biological
information.
what is the role of RNA
acts as a carrier of DNA - based information into dynamic cellular metabolism AS WELL AS playing catalytic roles
what is protein?
polymers of amino acids the main products of genes function as chemical machines to carry out cellular tasks, chemical and structural. Information has been translated into structural form
what are protein rna and dna all?
polymers of building blocks(nucleotides and amino acids)
what is dnas code?
linear code ≅ one - dimensional information
what is rna role in codes
functions to carry linear code and also folds into 3 - dimensional molecules
what is proteins shapes
fold into 3 -dimensional shapes, arranging chemical groups in space
what is DNA
deoxyribose nucleic acid
the molecule that stores and
transmits biological information in
the form of genes
DNA is a linear polymer of
deoxyribonucleotides, formed by
condensation polymerization
It possesses a double stranded
structure comprised of two
complementary strands basepaired together(double helix structure)
what are the building blocks of dna?
sugar phosphste (backbone)
base(hydrogen bonded base pair)
nucleotide
what does the sequence of nucleotides contain?
information content of the genes
how is the nucleotide sequence read and decoded?
nucleotide sequence is read in triplets and decoded by ribosomes for synthesis of proteins during the process of translation
during what process is nucleotide read and decoded?
translation
how does dna self regulate?
DNA also contains information
for its own regulation
Specialized DNA sequences, bind
to proteins that regulate
what does transcription contain
promoters and enhancers
what does replication contain
origins of replication ,telomeres
what does segregation contain
centromeres
is DNA information content solely directed towards encoding genes?
no
what does DNA represent?
a storage form of information
what happens to DNA information?
It is transcribed into RNA by RNA polymerase
Why is dna transcribed into rna?
in order to carry out function in the cell, a condensation polymerization
name 5 types of RNA
- mRNA
- rRNA
- tRNA
- miRNA
- ncRNA
What is mRNA
transcripts of genes;
translated into protein
what is rRNA
structural and catalytic RNA that makes up ribosomes
what is tRNA
transfer RNA that adapts
amino acids for protein translation
what is miRNA
microRNA that regulates
gene expression
what is ncRNA
long non
-coding RNAs
that regulate genome function
where is the catalytic centre for protein synthesis?
it was discovered from solution of the structure of the ribosome that rna comprises the catalytic centre for protein synthesis
what are proteins encoded by?
the sequence of nucleotides in their gene
as proteins are the main functional machines of cells , what do the provide?
• catalysis – making and breaking essential bonds throughout metabolism • structure – from cellular filaments to hair and skin • motility – molecular motors and tracks • signaling – circuitry for sensing and conveying • transport – membrane channels •& etc
what are the building blocks of protein?
amino acids
What are amino acids?
small organic molecules that consist of an alpha (central) carbon atom linked to an amino group, a carboxyl group, a hydrogen atom, and a variable component called a side chain
where are amino acids polymerized?
on ribosome by
condensation reaction
–
dehydration reaction between • carboxylic acid • amino group
what forms the peptide bond backbone
• amide linkage
• constrained planar bond –
resonant character
• hydrophilic backbone
how many amino acids in protein?
20 genetically encoded amino acids
which amino acids are in acid functional group?
glutamic, aspartic
which amino acids are in bases functional group?
lysine, arginine, histidine
which amino acids are in alcohols functional group?
serine, threonine
which amino acids are in sulfhydryl functional group?
– cysteine
which amino acids are in amides functional group?
glutamine, asparagine
which amino acids are in aliphatics functional group?
alanine , valine, leucine,
isoleucine, !methionine!
which amino acids are in special functional group
glycine, proline
what is proteins primary structure?
• linear arrangement of amino
acids
what is proteins secondary structure?
• regular spatial organization of
amino acid segments
what is proteins tertiary structure?
• three-dimensional “folded”
shape of protein
what is proteins quaternary structure?
• stable associations of multiple
protein molecules
what is acquisition of high order structure in protein known as?
protein folding
how does protein folding occure?
•Can be spontaneous or
catalyzed by “chaperones”
what are oligomeric proteins?
Oligomeric proteins, by definition, are composed of more than one subunit (polypeptide chain)
what illustrates serveral principals of protein structure?
hemoglobin
what is oligomeric structure?
tetramer
of alpha and beta hemoglobin
what is a lingand binding?
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose
the ligand is usually a molecule which produces a signal by binding to a site on a target protein.
where is the ligand binding in hemogloban
O2
what is a mutation that can occur in hemoglobin?
sickle cell anemia
what is the gene family structure in hemoglobin?
– alpha and
beta hemoglobin, related
myoglobin
where do nucleic acids initiate at in a polynucleotide chain?
Nucleic acids initiate at the 5’ end
of a polynucleotide chain.
which direction do RNA AND DNA always proceed?
DNA/RNA polymerization always
proceeds in the 5’
à 3’ direction
how does protein synthesis occur?
Protein synthesis occurs by
adding new amino acids to the
carboxyl of the preceeding
residue
where do protein start and end in their termini
Proteins start at their NH2 - termini and end at their COOH - termini
what general formula do carbohydrates follow?
(CH2O)n
what is n between in carbohydrates formula for simple sugars or monosaccarides?
3-7
what is the primary functionality of carbohydrates?
hydroxyl = OH group is the
primary functionality of
carbohydrates
what groups do monosaccharides include?
monosaccharides include C=O
groups and are either •aldoses = aldehyde groups •ketoses = ketone groups
what is a key feature of understanding carboydrates functionality?
stereochemistry of
carbohydrates is a key feature of
their functionality
what plays a key role in metabolism?
trioses play a key role in
intermediary metabolism • glyceraldehyde • dihydroxy acetone
what are the most biologically important carbohydrates?
most biologically important
carbohydrates are hexoses, e.g. • glucose • galactose
what is a key pentose involved in nucleic acid structure?
ribose
are most carbohydrates are cyclized
in biological systems?
yes
what are carboydrates polymerized to form?
carbohydrates polymerize to
form oligosaccharides and
polysaccharides
what do oligosaccharides include?
• oligosaccharides include
important dietary components
• sucrose
• lactose
what is sucrose?
disaccharide sugar,
major dietary
constituent/problem
what is lactose?
– “milk sugar”; deficiency
of lactase leads to lactose
intolerance
what do polysaccharides provide?
- energy storage: starch, glycogen
- structure: cellulose, chitin
- recognition: on glycosylated proteins
are lipids polar or nonpolar?
nonpolar
what are lipids?
Lipids are non-polar organic
compounds with limited solubility
in water
what are the two main types of lipids?
- aliphatic derivatives
* fused ring compounds
what are aliphatic derivatives lipids?
open
chain compunds derived from
fatty acids (e.g. oleic, stearic acids)
what are fused ring compund lipids?
steroids, including cholesterol and
steroid hormones
what are acyl glycerols –
– esters of fatty acids and glycerol; major
constituents of cell membranes and of fat
what are steroids?
– specialized components of membranes
(cholesterol) and key hormones
what are fatty acids?
alkyl chains of
varying length terminated by a
carboxylic acid group
what is the structure of lipids?
The structure is typically made of a glycerol backbone, 2 fatty acid tails (hydrophobic), and a phosphate group (hydrophilic).
what is a saturated fatty acid?
no double bonds
what is an unsaturated fatty acid?
contains double bond
what do acyl glycerols and
phosphoacyl glycerols form ?
the major structural
components of biological
membrane
what do Triglycerides function as?
energy storage
what is the function of •Phosphoglycerides
membranes, signaling
what is hydrophobic?
not soluable in water
what is hydrophillic?
soluable in water
are lipids hydrophobic or hydrophillic?
hydrophobic
are polar groups hydrophobic or hydrophillic?
hydrophilic
what happens if you combine hydrophobic and hydrophillic molecules?
combining groups creates
bifunctional molecules
–
amphipathic
what is amphipathic
combining groups creates
bifunctional molecule
what are micelles?
• at a critical concentration amphipathic compounds form higher order structures –these orient groups according to interaction with water
•these principles underly the
structure of biological membranes
what structure do micelles form?
•Double layered structure – lipid bilayer
what are biological membranes formed from mainly?
• biological membranes are
formed mainly from phosphoacyl
lipids that arrange in a bilayer
much like an extended micelle
why do membranes form barriers?
to diffusion
in the aqueous environment
what does membranes forming barriers to diffusion
in the aqueous environment allow?
•This allows selective permeability or
entry/exit of molecules into the
cellular environment
why do proteins associate with membranes?
to modify their properties
what do •peripheral proteins do?
bound to the
surface of membranes
what do •integral proteins do?
dissolved in
membrane, often spanning it
what do membrane proteins provide for the cell?
crucial functions
what are the crucial functions that membrane proteins provide for the cell?
• regulated transport – of nutrients
and ions
• cellular recognition
– specifying
cellular identity
- Cell signaling
- cell adhesion
- excitability
what is the cell?
the basic unit of all living species
what did virchow discover about cells?
All cells arise only from pre -existing cells (Virchow) – through mitosis/binary fission
who is credited with formulation of the cell theory?
•M Schleiden and T Schwann
what is cell theory?
1. All living organisms are composed of one or more cells 2. The cell is the most basic unit of life 3. All cells arise only from pre -existing cells (Virchow) – through mitosis/binary fission
what are prokaryotes?
– bacteria and
archea – are the simplest cells
what do prokaryotes consist of?
membrane that
encloses the cell
• a cell wall that provides stability
and support for the membrane
• a cytoplasm containing the
genome – DNA – and the
machinery for growth and
replication
what to eukaryota comprise of?
eukaryota comprise species
that possess nuclei and other
membrane bound organelles
within their cytoplasm
how did eukaryotic cells originate?
• originated through cellular
symbiosis = endosymbiosis
theory
what does the nucleous harbor?
genome of the cell
which organelles posses their own genomes?
•mitochondria and
chloroplasts and nucleous possess their
own genomes, including
ribosomal genes
what are the 3 major groups of eukaryotic cells?
: plants,
animals and fung
function of mitochondria
energy
metabolism/oxidative
phosphorylation
function of chloroplast
– energy
metabolism/photosynthesis
function of endoplasmic reticulum
membrane
system throughout the cell, regulates
protein synthesis, ionic homeostasis
function of • golgi apparatus
organizes
transport to membrane
function of •lysosomes
compartment for
intracellular digestion, containing
numerous hydrolases
function of • peroxisomes
compartment for
various oxidative enzymes
function of endosomes
trafficking vesicles
what is the cytoskeleton
eukaryotic cells also contain a
network of filamentous organelles
collectively known as the
cytoskeleton
what is the • actin filament network
functions in cell motility, analogous
to muscle at a microscopic scale
what is the function of microtubules
– provide cell structure and intracellular transport; also cell motility through cilia and flagella and the mitotic spindle
what is the function of intermediate filaments?
– provide
structural support in nearly all
animal cells; major filament of skin
and hair
what is cell differentiation
the process
of acquisition of distinctive cell
fate
how many cell types do humans contain roughly?
200+
what do transcriptional programmes
determine
gene expression
patterns and cell fate
determination
how do animal cells reproduce?
by
duplicating their components
and undergoing fission
what occurs during animal cell reproduction
precisely duplicate the
genome and segregate it into
daughter cells
when does DNA replication take place?
during the s phase chromosomes are duplicated
what phase are chromosomes segregated?
m-PHASE
what seperates cells into daughters
cytokinesis
what is G1(gap 1)
follows mitosis and
is a period of growth prior to S
-
phase
what is G2(gap 2)
is a period of
preparation for mitosis following S-phase
what are 3 types of filament?
- actin filament(microfilament) - twisted two strand structure
- microtubule-hallow tubes
intermediate filaments-rope like structure
in 1945 who won the nobel prize for the discovery of penicillian?
Dr Alexander flemming
why did domagk recieve tge nobel prize in 1939?
for the discovery of the antibacterial effects of prontosil
who discovered stretomycin?
schatz and waksman
what problem arose with antibiotics very quickly?
resistance to antibiotics
what will happen by 2050 if no new antibiotics are discovered?
antimicrobial resistance deaths will be so high it will surpass the deaths cause by cancer
how many distinct lineages of cells have been discovered?
3 phylogenetically distinct lineages of cells have been identified
what is another term for lineages?
domains
what causes lineages?
evolutionary diversification
what are the 3 domains of life?
1: eukaryotes
2: bacteria
3: archaea
what are the 3 macro organisms?
animals fungi and plants
what are the crown species?
eukaryotic
are all prokaryotes closely related?
no
are archaea more closely related to eukaryotes or bacteria ?
eukaryotes
what are prokaryotic microorganisms?
bacteria and archaea
what are eukaryotic mircroorganisms?
fungi, protozoa, algae
what are non cellular microorganisms?
viruses
features of prokaryotes?
no nucleus
cell wall
no cell organelles
what are features of eukaryotic cells?
nucelus
no cell wall
cell organelles
what is a genome?
The bacterial genome or chromosome contains the bacterial genetic information. Plasmids may also be present
what is cytoplasmic membrane
The cytoplasmic membrane surrounds the cytoplasm
Vital cell structure which acts as a barrier between the cytoplasm and environment
Highly selective permeability barrier involved in nutrient uptake and excretion of metabolic waste products
what is the cell wall
Rigid layer surrounding the cytoplasmic membrane
what is the outer membrane of gram negative bacteria?
Covers the cell wall and acts as a molecular sieve
what will a gram positive cell surface look like
smooth
what will a gram negative cell surface look like?
ridges /textured
what would a break in the cell membrane result in?
loss of cell integrity and lysis
what is a cell membrane composed of?
lipids and phosphates primarily (phospholipid bilayer
also some proteins
describe the cell wall in terms of hydrophillic and hydrophobic
the outer layers of glycerol and phosphates are hydrophillic
the inner layer of fatty acids are hydrophobic
why is the core of the cytoplasmic membrane hydrophobic?
Hydrophobic core of cytoplasmic membrane prevents water soluble nutrients leaking out of the cell
why could the hydrophbic core of cytoplasmic membrane be a bad thing?
it prevents nutrients diffusing into cell
how is the prbroblem of the Hydrophobic core of cytoplasmic membrane preventing nutrients diffusing into cell solved
Requires special transport proteins in the membrane
what do bacterial cells contain a high levvel of?
high concentrates of dissolved solutes(salts sugars etc)
what is the function of the cell wall
Generates a high pressure within the cell caused by the cytoplasm pressing against the cell envelope (similar to pressure in car tyre)
1Cell wall allows cell to withstand turgor pressure
2Gives the cell shape and rigidity
what is peptidoglycan
the principal component of the cell wall, is a
unique polysaccharide which gives the cell its characteristic
shape and prevents osmotic lysis
what is gram positive bacterial cell wall
Many peptidoglycan layers
90% of cell envelope material
what is a gram negative cell wall?
One peptidoglycan layer
2-20% of cell envelope material
