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Biology Notes
Topic 2
The role of mucus in the lungs
Lung function:
Dust, debris or microorganisms gets trapped in the mucus
...


People with CF has less water in their mucus (sticky) is it’s
hard for cilia to remove it
...

-

Made of protein fibres in a jelly like
protein carbohydrate mix

Epithelial cell has two membranes:
1
...


Apical membrane (away from
basement membrane)
Basal membrane (in contact with
basement membrane)

Two types of epithelium:
1
...

-

Columnar:
Small intestine
Epithelial cells extend out from the basement membrane
Surface facing the lumen is normally covered with microvilli
(increasing surface area for absorption)

Trachea, bronchi and bronchioles have ciliated epithelial cells with
cilia on the apical surface
...

= pseudostratified (appears to have several layers, when there’s in fact
one, due to nuclei being in different parts of the cells)

-

-

Air is drawn in- trachea
Low pressure due to increased vol
...

-

Acid in the stomach kills microorganisms that are swallowed

People with CF have sticky mucus, so it can’t be removed easily
...

-

Repeated lung infections weaken the body’s ability to fight pathogens
Damages the structures of the gas exchange system

How sticky mucus reduces gas exchange
The effect of increase in size on surface area
Unicellular organisms:
Whole cell surface membrane is the gas exchange surface
Substances diffuse down a concentration gradient (high to low)
Gradients are maintained by the cell continuously using
substances absorbed and producing waste
Larger organisms:
More exchange need to take place
More problems absorbing substances because of their surface area to volume ratio
Total surface area divided by its volume
Diffusion isn’t enough because distance to innermost tissues is too far for it to be efficient and fast
Gas exchange surfaces
A steeper concentration gradient = faster gas exchange
...
Greater gradient = faster diffusion
...


How sticky mucus affects gas exchange
Mucus layer in the bronchioles blocks the airways- blockages are more
likely at the ends of the airways
-

Air can’t move into the alveoli, past the blockage
Number of alveoli allowing gas exchange reduces

Air can pass when person breathes in, but not when they breathe out
...

People with CF find exercise hard as their gas exchange isn’t efficient
...
It’s caused by a faulty transport protein channel in the membrane
...
Plants can make
all amino acids commonly found in proteins but animals need to
obtain some through diet (essential amino acids)
...

Alanine has a methyl R-group (-CH3)
Some R-groups can have complex carbon ring structures
R-groups can contain nitrogen or sulphur atoms
1
...


1
...

Alpha-helix:
-

hydrogen bonds form between the slightly negative C=O (carboxylic
acid) and slightly positive –NH (amine group of amino acid)
stabilises the shape

Beta pleated sheet:
Amino acid chains may fold back on themselves/several lengths of the chain
...


Tertiary structure

Polypeptide chain folds again into a precise 3D shape
...

R-groups are polar when sharing of electrons is uneven
...
Non-polar groups are hydrophobic
...
Disulphide and
ionic bonds are stronger than hydrogen bonds, but are sensitive to PH
...

Some proteins may only be functional if they’re made
up of several polypeptide chains held together
...


-

Single chain proteins can’t have a quaternary
structure- they need more than one
polypeptide chain to have a quaternary
structure
...
E
...
Polypeptide chains that make
up myoglobin and haemoglobin are associated with an
iron-containing group
...


Globular proteins

E
...
Enzymes- their 3D shape is crucial for their ability to form enzyme-substrate complex and catalyse reactions in
cells
...

-

Soluble (hydrophilic side chains that project from
the outside of the molecules)
Important in metabolic reaction

3D shapes of globular proteins are important for their roles
in binding to other substances
...


2
...

-

Cross linking between peptide chains adds extra
strength
Insoluble
Structural

E
...
keratin in hair and skin, collagen in skin, bones, tendons,
blood vessels
...

-

A phospholipid has only two fatty acids (a negatively charged phosphate group replaces the third fatty acid)

Phosphate head
-

Hydrophilic

Fatty acid tails
-

Hydrophobic

The head is polar so it attracts
other polar molecules
...


More electron dense- darker
edges

Lighter part on a
micrograph
...

-

Tails may form a layer on the surface
sticking out of the water
Spherical clusters = micelles

A bilayer is formed because the two fatty acids are
too large to fit into the middle of a micelle
...

-

The bilayer will tend to close on itself so there are no exposed chains

Cells are filled with aqueous cytoplasm and are surrounded by aqueous tissue fluid so the phosphate heads are on the
outside and hydrophobic tails are on the inside
...


Some proteins are fixed within the membrane but others are not and can move around in the fluid phospholipid
bilayer- fluid mosaic model
...

2
...

2
...

Inner layer is coated in heavy metal
3D images reveal a smooth mosaic like surface (lipid tails) interspersed by larger particles (integral proteins)

Labelled molecule test
Plant proteins (lectins) bind to polysaccharides- labelled with ferritin (protein with ferric oxide core)
...

-

Showed membrane is asymmetric (outside different to inside)
Doesn’t support to sandwich model (lectin would have bound to outside and inside)

Fusing mouse cells with human cells
Mouse protein- green label
...
Cells fused…
40 minutes
37 degrees

Complete intermixing is only possible by diffusion through the membranes- proves its fluid
...

Kinks in the hydrocarbon tails prevents them
packing closely together- more movement is
possible
...


Glycoproteins and glycolipids have important roles in cell-cell recognition/ as receptors
...


Diffusion

‘’passive, net, random movement of molecules or ions from a region of high
concentration to a region of low concentration’’
NOTE: its net movement because its random movement so it’s likely the
particles move to area of low concentration but not all of them do
...


Facilitated diffusion
Hydrophilic (polar) molecules and ions that are larger than carbon dioxide can’t diffuse
...

-

Different channel proteins for different molecules
Specific shape allows one type of ion or molecules

A signal for opening/closing a gatedchannel could be:



Hormones
Change in potential difference (voltage)

Carrier proteins change shape when the molecule binds to a specific site on the
protein, allowing it across
...

-

Molecules move from high to low concentration as more frequent binding to carrier proteins with higher
concentrations
...


3
...

Fewer free molecules are able to collide with/move
across the membrane
...


4
...

-

Carrier proteins also needed

Energy supplied by the transfer molecule ATP (adenosine triphosphate) which provides
immediate energy for all biological processes
...

-

The removed phosphate group becomes hydrated and a lot of energy is released as bonds form between
water and the phosphate
...

Active transport proteins can be called pumps and a
...
can occur within the cell- e
...
between mitochondria and
cytoplasm
...


Exocytosis and endocytosis

Large molecules/particles or large quantities of molecules need to be transported across a membrane = bulk
transport which relies on fluidity of membrane
...
g
...
g
...
g
...
People with CF struggle to regulate the viscosity of the mucus- too sticky so it
can’t be moved by the cilia
...


1
...

Carrier proteins in the basal membranes of the epithelial cells actively pump sodium ions out of the cells
...

-

Concentration of Na+ ions increases in tissue fluid
Creates a potential difference between tissue fluid and mucus (electrical gradient)
Negatively charged chloride ions diffuse into the tissue fluid through gaps between neighbouring epithelial
cells- electrochemical attraction
...
In the cell is higher)

Movement of mucus from lots of small bronchiole branches to few large bronchioles means water must be removed
to reduce volume of mucus- avoiding flooding larger airways
...


TOO LITTLE WATER IN THE MUCUS

Chloride ions are transported across the basal membrane into the epithelial cell = concentration gradient- chloride
ion concentration is higher in the cell than out
...

-

Cl- ions diffuse out through the CFTR protein down the concentration gradient into the mucus
...
This movement of sodium and
chloride ions into the mucus draws water out of the cells by osmosis until solutions are isotonic
...


WHY CF LUNGS CAN’T REGULATE WATER IN MUCUS
CFTR protein may be missing or it doesn’t function correctly
...
Build-up of mucus reduces the effective ventilation of
alveoli
...


DIGESTIVE SYSTEM

CF sufferers can’t maintain body mass because they have problems with digestion and
nutrient absorption
...

-

Food supplements containing digestive enzymes help break down large food
molecules
...

Glands: secrete digestive enzymes into the lumen of the gut- catalysts to break down
extracellular breakdown of food molecules
...
They’re delivered to
the gut in pancreatic juice released form the pancreatic duct
...
g
...

= cysts of hard, damaged tissue in the pancreas
If insulin releasing cells within the pancreas are damaged, diabetes can result
...

-

Only a few amino acids may be directly involved in the
active site
The remainder maintaining the 3D shape of the
protein molecule

Lock and key theory
A molecule with a complementary
shape to the active site can sit
...

-

Enzyme is never changed

Each enzyme catalyses one specific reaction because only one
shape of substrate will fit into its specific active site
...
When the substrate enters the active
site, the enzyme molecule changes shape slightly to fit more
closely around the substrate
...


Activation energy
To convert substrate into products, bonds much change in and between molecules
...

Activation energy is the energy needed to break bonds and
start a reaction
...

-

Without an enzyme, heating a substrate would
provide this energy
...


Enzymes catalyse:
-

Intracellular reactions (inside cells) where enzymes can be free floating or attached to membranes
Extracellular reactions (e
...
tissue fluid, blood/ other aqueous solutions)
Catabolic reactions(breaking down of large substrate molecules)
Anabolic (building) reactions e
...
fatty acid
Enzymes…
synthetase enzyme complex that synthesises
fatty acids within cells
...

Don’t get used up
Bind with another substrate molecule

Effect of CF on the reproductive system
CF females- reduced chance of becoming pregnant because
mucus blocks the cervix so the sperm can’t reach the egg
...
If the sperm ducts are present,
they can become partially blocked by mucus- fewer sperm are
present to ejaculate
...

Without CF: CFTR and ENaC (sodium ions) allow reabsorption of sodium chloride from the sweat as it moves up the
duct towards the skin surface
...

-

Saltier sweat means the CFTR and ENAc proteins aren’t absorbing the Na+ and Cl- ions like they shouldindicating cystic fibrosis

How is the CTFR protein made?
-

CF is caused by a mutation in the DNA that
carries instructions for making the CFTR protein

Structure of DNA
DNA is present in the nucleus of cell- if there’s no nucleus
then it’s in the cytoplasm
...
It’s a long chain polymer made of many units called nucleotides
or mononucleotides
...


Nitrogen containing base is the only part of the nucleotide that is variable- four bases:
-

Adenine
Cytosine
Guanine
Thymine

Mononucleotides link together by condensation
reactions between the sugar of one nucleotide and the
phosphate of the next one = polynucleotide
...

DNA has two polynucleotide strands twisted around
each other to form a double helix
...

Bases are held together by hydrogen bonds
...

Why do the babes pair up?
Bases A and G have a two ring structure
Bases C and T have one ring
...
The shape and chemical
structure dictates how many hydrogen bonds each one can form
...
It instructs the cell to make the CFTR
protein that forms the transmembrane chloride channel
...


Every gene is a sequence of bases on a DNA molecule coding for a sequence of amino acids in a polypeptide chain
...


From DNA to proteins (protein synthesis)
DNA is in the nucleus but proteins are made in the cytoplasmDNA can’t pass through the membranes surrounding the
nucleus into the cytoplasm
...


Transcription

-

Takes place in the nucleus

-

A copy of the required gene (for the specific protein) is
made by RNA – ribonucleic acid
RNA leaves the nucleus and carried information to the
cytoplasm
Original gene stays in the nucleus

Difference between DNA and RNA
RNA:
-

Single stranded polynucleotide
Made of ribonucleic acid
Ribose sugar instead of deoxyribose
Uracil replaced Thymine
A section of an RNA molecule folds back on itself and
complementary bases pair up so it can appear double
stranded but it’s not

The RNA made during transcription is known as messenger RNA (mRNA)
...

-

The template strand is transcribed to make an mMRNA with the same base sequence as the DNA coding
strand
Complementary RNA nucleotides align themselves into position
Phosphodiester bonds form to produce an mMRNA molecule
Only the section of DNA coding for the required protein is transcribed
mMRNA molecule leaves the nucleus through a pore in the nuclear envelope
DNA molecule zips up

SENSE STRAND:
DNA coding strand
ANTISENSE STRAND:
template strand

Protein synthesis- translation
Turning base sequence into a sequence of amino acids
...

This could change the amino
acid sequence of the primary
structure- alters the 3D
structure and properties
...

Deletion:a base is removed- frame shift- bases following are affected
...

Translation of the code
In the cytoplasm, the mMRNA attaches to a ribosome
...

-

Ribosomes are small organelles (structures within a cell) made of ribosomal RNA and protein
...


tRNA molecules are made of single stranded RNA but can fold back on themselves and the
complementary base pairing makes them a clover leaf shape
...

The anticodon sequence is complementary to the mRNA codon for a particular amino acid
...

-

Each amino acid has its own specific tRNA which carries it to the ribosome
...
The tRNAmolecule carrying this amino acid has the complementary
anticodon UAC and hydrogen bonds hold it to the start codon
...


Once the peptide bond is formed, the ribosome moves along to expose a new codon at the binding site
...

tRNA is never used up- just transports amino acids to the ribosome

The stop codon (chain terminator) could be UAA, UAG, UGA
...

DNA replication
During cell division, an exact copy of the DNA must be produced so each daughter cell receives a copy = replication
-

Entire DNA double helix unwinds and the strands split apart
Hydrogen bonds between bases break
Free DNA nucleotides line up along each single DNA strand- hydrogen bonds form between bases

Enzyme DNA polymerase links adjacent nucleotides with phosphodiester bonds in condensation reactions to form
new complimentary strands
...


How do we know its semi-conservative?
1
...

3
...

-

All the nucleotides in the bacteria at the start contained heavy nitrogen, making the DNA denser than
normal (yellow)

Meselson and Stahl then moved the bacteria into a medium containing only normal 14N
...


-

They allowed the bacteria to divide and their DNA to replicate once
...


Heavy DNA (only 15N) sinks to the bottom and light DNA (only 14N) collects near
the top
...

Result:
-

Single band of medium density DNA

No heavy DNA- conservative replication rejected
...


The DNA was extracted and centrifuged after two rounds of replication, giving
two bands- one medium and one light
...


Fragmentational replication would only produce one type of DNA containing a mix of heavy and light nucleotides
...

Mutations can occur in the DNA of an ovary or testis cell that’s
dividing to form an egg or sperm
...

Large amounts of DNA in a cell don’t play a role in protein synthesis
and so mutations here have no effect
...

-

Adenine replaces thymine at one position along
the chain
mRNA codes GUA instead of GAA
result: protein produced contains non polar amino
acid valine rather than polar glutamic acid
haemoglobin becomes less soluble (not polar)
when oxygen is low, the molecules form long fibres that stick together inside the red blood cell- distorts the
shape
...


Mutations and cystic fibrosis
CF gene is a section of DNA on chromosome 7 carrying the code to make the CFTR protein
...
g
...
Every cell (except sex cells) contain
two copies of each gene- one form each parent
...

Humans have 23 pairs of chromosomes in our cells; chromosomes in each pair are
homologous chromosomes (one from dad, one from mum)
...

-

Normal allele coding for the functioning CFTR protein (F)
Mutated allele producing non-functional protein (f)

Possible combinations:
1
...

3
...

Ff- a carrier and could have children with the disease

The alleles that a person has make up their genotype
...

If both parents are carriers…
1 in 4 (25%) chance that the baby will have the genotype ff and have cystic fibrosis
...

-

People with CF are more likely to reach adulthood now but most have reduced fertility because the mucus is
too sticky in the reproductive system
...


Inheritance
Cystic fibrosis = monohybrid inheritance
...

e
...
thalassemia
-

Affects production of haemoglobin
Caused by recessive alleles on chromosome 11
Different mutations can affect the gene

Someone who is homozygous for one of these recessive
alleles makes no haemoglobin, or some that can’t carry out
its function
...
Thalassemia is common where
malaria occurs (e
...
Mediterranean sea)
...
Someone heterozygous for this condition will show restricted growth
...


Incomplete dominance
Sometimes neither allele is dominant, and so heterozygotes have an
intermediate phenotype
...
g
...
It produced pink flowersintermediate between white and pink
...


TESTING FOR CYSTIC FIBROSIS
Genetic testing
= identifying the abnormal allele of the gene in the DNA of any cells
...


Genetic testing can be performed on any DNA- cheek cell or white blood cell samples can be taken from the parents
and have the DNA tested to see if they’re a carrier of the disease
...

How can genetic screening be used?
1
...


Identify carriers

-

Sample of blood or cells taken from the inside of the mouth to detect abnormal alleles in people who are
heterozygous (without the disease)
Valuable in a family with a history of CF- assesses probability of having a child with the disease
Counselling offered before and after testing so parents can make informed decisions

3
...
You insert a
needle into the amniotic fluid to collect fetal cells that
have fallen off the placenta and fetus
...


-

Chorionic villus sampling (CVS):
Second invasive technique
...
Carried out between 8-12 week as no need for amniotic fluid to develop
...


-

Non-invasive prenatal diagnosis (NIPD)
Analyses DNA fragments in the mothers blood plasma during pregnancy- most is form the mother but 10-20%
will be from the embryo
...
Samples are better collected at 7-9 weeks of pregnancy depending on
the test
...

e
...
mother may not have a condition but it’s thought the fetus may have inherited it
...
If found, we know the
embryo has inherited the condition
...
Sperm mutation is common in older fathers
...

-

Cell-free DNA is isolated form the mother’s blood and screened
...


NIPD has also been used for diagnosis of chromosomal conditions such as Downs Syndrome
...

-

Pre-implantation genetic diagnosis (PGD)

It is an option for a couple with a family history of a serious genetic condition
(like CF)
...


-

The DNA of the cell is analysed and the results are used to decide whether to
place the embryo into the uterus
...


Medications to relieve symptoms

-

Early diagnosis and treatment of lung infection is vital
Antibiotics kill/prevent growth of bacteria in the lungs

-

Antibiotics

inhaled using a nebuliser
...

Drugs relax muscles in airways
Open airways up, relieve tightness in the chest

-

Bronchodilators

-

Infection of the lungs leads to the accumulation of white blood cells in the mucus
The breakdown of white blood cells released DNA which adds to the stickiness of the
mucus
Inhaled using a nebuliser
The enzymes break down he DNA so mucus is easier to clear form the lungs

-

Reduce inflammation of the lungs

DNAase enzymes

Steroids
2
...

-

No cure for CF!!!



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