Topic 2- Notes Flashcards

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1
Q

trachea, bronchi, bronchioles, alveoli

Do they have cartilage?

A

Trachea - c-shaped rings to keep airway open
Bronchi - irregular blocks
Bronchioles/alveoli - none

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2
Q

do trachea, bronchi, bronchioles and alveoli have ciliated epithelium?

A

Trachea, bronchi, bronchioles yes

Alveoli - they have simple squamous epithelium

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3
Q

Do trachea, bronchi, bronchioles and alveoli have mucous glands?

A

Trachea - goblet cells secrete mucus
Bronchi - fewer goblet cells
Bronchioles - none
alveoli - none

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4
Q

do trachea, bronchi, bronchioles and alveoli have elastic fibres?

A

Trachea - few

Bronchi, bronchioles, alveoli - yes

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5
Q

Do trachea, bronchi, bronchioles and alveoli have smooth muscle?

A

alveoli - no

the rest - yes

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6
Q

Do trachea, bronchi, bronchioles and alveoli have macrophages?

A

All - yes

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7
Q

How is diffusion aided in the alveoli?

A

Large SA
thin squamous epithelium .
surrounded by blood capillaries

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8
Q

What are epithelium?

A
  • A tissue
  • Found on outer surface of many animals and the surfaces of organs cavities and tubes
  • Can be squamous (flattened and v thin or columnar (extended in height)
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9
Q

Epithelium function

A

Move mucus (and other trapped dust/microbes) up and out of lungs to throat, here it is swallowed.
Microorganisms destroyed by acid in stomach.
Goblet cells in ciliated epithelium, trachea and bronchi produce mucus which traps inhaled particles

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10
Q

2 problems caused by the sticky mucus produced by CF patients

A

1) Increase chances of lung infections: bacteria collect in mucus - too sticky for cilia to move therefore mucus builds in airways - stickier. Harder for white blood cells to fight - weakened.
2) Decrease in gas exchange efficiency: sticky mucus builds in bronchioles preventing ventilation to alveoli below: reducing no. working alevoli can lead to damage , elasticity, lungs

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11
Q

Fill in the gaps:
The actual respiratory surface is on the A inside the lungs. An average adult has about 600 mil alveoli, giving a total SA about 100m2, so the A is huge. The walls. the alveoli are composed. a single layer. flattened B cells, as are the walls. the capillaries, so gases need to C through just 2 thin cells. D diffuses from alveoli cells into the alveoli so that they’re always moist. E dissolves in this water before diffusing through the cells into the blood, where it’s taken up by F in the red blood cells. the water also contains a soapy G (a mixture of H molecules) with I its surface tension and stops the alveoli J. The alveoli also contain phagocyte cells to kill any K that’ve not been trapped by the L.

A
A - alveoli
B - epithelial
C - diffuse
D - water
E - oxygen
F - haemoglobin
G - surfactant
H - phospholipid
I - reduces
J - collapsing
K - bacteria
L - mucus
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12
Q

What is fick’s law?

A

rate. diffusion SA x difference in conc/thickness. the gas exchange surface

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13
Q

What 3 properties of gas exchange surfaces is the rate.diffusion dependent on?

A

SA - rate.diffusion is directly ? to the SA. As SA increases, rate.diffusion increases.
Conc.gradient - rate.diffusion is directly ? to the diiffernce in conc.across the gas exchange surface. Great conc.gradient leads to faster the diffusion.
Thickness of the gas exchange surface - rate.diffusion is inversely ? to the thickness of the gas exchange surface. The thicker the surface the slower the diffusion.

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14
Q

What are proteins?

What are some of their biological roles?

A

Proteins are a group of large/complex polymer molecules made up of long chains of amino acids.
Biological roles:
Structural: They’re the main component of body tissues e.g. muscle, sin, ligaments and hair.
Catalytic: All enzymes are proteins, catalyzing many biochemical reactions.
Signalling: Many hormone and receptors are proteins.
Immunological: All antibodies are proteins. Immunological means related to the immune system.
A protein consists of 1 or more polypeptide chain folded into a highly specific 3D shape.

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15
Q

Describe the primary structure of a protein

A

The order of amino acids joined together by peptide bonds in a polypeptide.
There are 20 different kinds of amino acid, and thus a vast no. combinations are possible

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16
Q

Tertiary structure

A

The precise shape formed by folding of the secondary structure - due to interactions mainly between R groups.
eg.
i) ionic bonds
ii) disulfide bridges between S-S of cysteines
iii) hydrophobic interactions (i.e. non-polar amino acids face inwards)
iv) hydrogen bonds

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17
Q

Quartenary structure

A

the linking of a no. of 3) folded polypeptide chains e.g. haemoglobin = 2 identical beta chains and 2 identical alpha chains.
More than one tertiary structure

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18
Q

What are conjugated proteins?

A

Proteins containing non-protein material e.g. each alph and beta chain has a heme (iron containing) group at the centre of the chain. The non-protein part is called the prosthetic group.

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19
Q

the Davson -Danielli model (held up to the 1970s)

a) Description
b) evidence for
c) evidence against?

A

a) consists of: a lipid bilayer where 2 layers of polar lipid molecules are arranged with the hydrophilic heads outwards. A layer of protein covering the surfaces of the membrane. lipids aren’t free 2 move.
3 layers - protein, lipid sandwich.
b) evidence from electron micrographs. Dark outer layers thought to be proteins and lighter areas thought to be lipids.
c) Doesn’t allow hydrophilic phosphate heads to be in contact with water.

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20
Q

Experiments to figure out where the proteins went on a model:
a) increase ionic strength.solutions/adding detergent/

A

peripheral proteins:
- loosely attached to outside surface of membrane
- some could be dissociated by low ionic strength
integral proteins:
- fully embedded within the phospholipids membrane
- some needed more action/adding detergent in order to dissociate

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21
Q

b) analysis of amino acid content of proteins?

A

some proteins have polar, hydrophilic amino acids at end of proteins with a non-polar hydrophobic amino acid in the middle.

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22
Q

c) Freeze fracture and scanning EM (electron microscopy) studies?

A

Sample is frozen- cut/split- showing outer and inner layers - inner coated in heavy metal.
3D images from EM scanning
found mosaic-like structure (lipid tails)
bumps = integral proteins

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23
Q

d) Use. lectins which bind to polysaccharides previously labelled with ferritin?

A
  • the lectins only bound to outer surface.

- Therefore membranes are asymmetric - not like the Davson Danielli model

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24
Q

e) Fusion. mouse and human cells to create hybrids?

A

Label same proteins in mouse with GFP (green fluorescent protein) and some proteins in human with RFP (red fluorescent protein)

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25
Q

Fill in the gaps:
Membranes are composed of A, B and C arranged in a D structure. The E form a thin, flexible sheet, while the proteins “float” in the F sheet like icebergs, and the carbohydrates extend out from the proteins.

The G are arranged in a layer 2 molecules thick, a H with their polar, hydrophilic I heads facing J and their non-polar hydrophobic K tails facing each other in the middle of the bilayer. This hydrophobic bilayer acts as a barrier to all but the smallest molecules, isolating the 2 sides of the membrane.

Different kinds of membranes can contain phospholipids with different L affecting the M and N of the membrane.

A

A) proteins H) bilayer
B) Lipids I) phosphate
C) carbohydrate J) outwards
D) phospholipid bilayer K) fatty acid
E) phospholipids L) fatty acids
F) phospholipid M) strength
G) phospholipids N) flexibility

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26
Q

Animal cell membranes also contain another vital lipid, what is it, and what is its role?

A

Cholesterol:

Maintains the fluidity of the membrane by affecting movement of the phospholipids

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27
Q

What is

a) exocytosis
b) endocytosis?

A

a) Used for bulk transport of substances OUT of the cell. Vesides fuse with the cell surface membrane, releasing their contents.
b) used for bulk transport of substances INTO the cell. Vesicles are created from the cell surface membrane, bringing their contents into the cell.

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28
Q

Summary of membrane transport:

method          Uses energy        Uses proteins    specific
Simple diffusion
Facilitated
 diffusion
Osmosis
Active Transport
Vesicles
A
Uses          Uses      Specific
energy      proteins
No               No         No
No               Yes       No
No              No         No
Yes              Yes       Yes
No               No        No  (it's the protein that makes it specific)
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29
Q

True or False

a) The neurotransmitter acetylcholine can activate a muscle cell and cause it to contract, even though the acetylcholine molecule never enters the cell because the acetylcholine receptor protein spans the plasma membrane.
b) Cholesterol molecules act to attach to carbohydrates.
c) The plasma membrane of animals contains carbohydrates on the side of the membrane facing away from the cell

A

a) True
b) False - alter the fluidity of the membrane
c) True

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30
Q

True or False?

a) Lipids form a barrier to the movement materials across the membrane.
b) The interior of the phospholipid bilayer is Aqueous
c) All proteins are anchored within the membrane
d) the amino acid side chains in the region of the protein that crosses the membrane are likely to be charged.

A

a) True
b) False - hydrophobic
c) False - many proteins can move around the bilayer
d) False - hydrophobic

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31
Q

Describe:

a) Proteins that span the membrane
b) Proteins on the inside surface of cell membranes
c) Proteins on the outer surface of cell membranes

A

a) They’re usually involved in transporting substances across the membrane.
b) they’re often attached to the cytoskeleton and are involved in maintaining the cell’s shape/in cell motility. They may also be enzymes, catalysing reactions in the cytoplasm.
c) they can often act as receptors by having a specific binding site where hormones/other chemicals can bind. This binding then triggers other events in the cell. They may also be involved in cell signalling and cell recognition/they may be enzymes, e.g. maltase in the small intestine (more in digestion)

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32
Q

where are the carbohydrates found in a cell membrane? (glycocalyx)

A
  • On the outside surface of all eukanyotic cell membranes and are attached to the membrane proteins/sometimes to the phospholipids.
  • They’re short polysacchaarides composed of a variety of different monosaccharides, and form a cell coat of glycocalyx outside the cell membrane.
  • The glycocalyx is involved in protection and cell recognition and antigens such as the ABO antigens on blood cells are usually cell-surface glycoproteins.
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33
Q

Where are proteins found in a cell membrane and what’s their structure?

A

They usually span from 1 side of the bilayer to the other (channel proteins), can also sit on one of the surfaces. Can slide around the membrane very quickly and collide with each other, but can never flip from one side to the other.
The proteins have hydrophilic amino acids in contact with the H2O on the outside of membranes and hydrophobic amino acids in contact with the fatty chains inside the membrane.
Proteins comprise about 50% of the mass of membranes and are responsible for most of the membranes properties.

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34
Q
What is osmosis?
Define:
a) isotonic solution?
b) hypertonic solution?
c) hypotonic  solution/
A
Osmosis is the net movement of water molecules from a solution of low conc. solute (high water conc.) to a solution of higher solute conc. (lower water conc) through a partially permeable membrane.
a) equally concentrated
b) higher osmotic pressure
lower water potential which = high solute conc
c) opposite to b)    
overall movement of water (arrow down): 
arrow down: hypo
arrow both ways: iso
arrow up: hyper
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35
Q

What is diffusion?

What can diffuse through a lipid bilayer?

A

The movement of molecules or ions from a region of high conc. to a region of low conc. by relatively slow random movements of molecules - until equilibrium.
Small uncharged particles, O2, CO2, non-polar and hydrophobic particles can diffuse through a lipid bilayer.
Diffusion across a membrane doesn’t require energy, it’s passive

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36
Q

Cell membranes are impermeable to most substances: Why is this important and what does it allow?

A

This property allows materials to be concentrated inside cells, materials to be excluded from cells or materials to be simply separated from the outside environment.
This compartmentalisation is essential for life, as it enables reactions to take place that would otherwise be impossible. Eukaryotic cells can also compartmentalisation materials inside organelles.
Obviously materials need to be able to enter and leave cells, and there are several methods by which substances can move across a cell membrane..

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37
Q

Globular and Fibrous Proteins

What are globular proteins?

A
  • 3D
  • Highly folded and compact spherical shape
  • Tertiary structure easily disrupted
  • Soluble-hydrophilic side groups on outer surface of the protein
  • Precise shape needed for molecular interactions
  • e.g. haemoglobin, antibodies, enzymes (protease), hormones (e.g. insulin)
  • regular repetitive sequences of amino acids
  • highly specific
  • Always identical between 2 e.g. of the same protein
  • metabolic functions.
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38
Q

What are fibrous proteins?

A
  • composed of many polypeptide chains, chains are long and held together (often by H bonds)
  • several polypeptide chains can be cross linked - stable
  • usually insoluble
  • they’re important for structural strength
  • e.g. keratin in hair, callogen in skin and bone
  • irregular amino acid sequences
  • sequences may vary
  • long parallel strands
  • length of chain may vary
  • support and structural functions
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39
Q

What does anabolic and catabolic reactions mean?

A

Anabolic reactions: building up

Catabolic reactions: building down

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40
Q

What is mucus like in non-CF sufferers /production?

A

Cells that line airways produce mucus.
Water content of mucus continuously regulated to maintain constant viscosity, the mucus.
Must be runny enough to move by cilia, not too runny so it floods airways.
Regulation - water content maintained by transport. sodium ions and chloride ions across epithelial cells.
Water follows ions by osmosis.

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41
Q

Organisms affected by CF:

Airways

A

Clogging and infection of bronchial passages impede breathing. The infections progressively destroy the lungs. Lung disease accounts for most deaths from CF.

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42
Q

Liver:

A

Plugging of small bile ducts impedes digestion and disrupts liver function in perhaps 5% of patients.

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43
Q

Pancreas

A

Occlusion of ducts prevents the pancreas from delivering critical digestive enzymes to the bowel in 65% of patients. Diabetes can results as well.

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44
Q

Small intestine

A

Obstruction of the gut by thick stool (constipation, faeces), necessitates surgery in about 10% of newborns.

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45
Q

Reproductive tract

A

Females have less chance of becoming pregnant - mucus plugs develop in the cervix - stops sperm reaching the eggs. males with CF usually the vas deferens (sperm ducts) meaning sperm can’t leave the testes/vas deferens can become partially blocked by a thick sticky mucus layer. Fewer sperm present in each ejaculation.

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46
Q

Skin

A

Sweat glands are exocrine gland, initially secrete into their lumen a solution of salt and water that’s isotonic to the blood. n an individual without CF, CFTR and ENaC proteins allow respiration of sodium chloride from the sweat as it moves up the duct towards the skin. The sweat that’s released on to the skin and evaporates if therefore hypotonic. (measurement of chloride in sweat is a mainstay of diagnosis)

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47
Q

Enzymes: write a definition for each:

biological catalyst

A

Enzymes are biological catalysts; they are protein carriers that speed up chemical reactions in living organisms. Different chemical reactions within cells are catalysed by specific enzymes. Without these enzymes, the reactions would take place very slowly at the temperature inside cells.

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48
Q

Activation energy

A

Before a chemical reaction can take place, bonds must be broken. This requires energy. This activation energy is normally provided by heating the substances involved in the reaction. Enzymes reduce the activation energy for a reaction, so reactions in living organisms can take place at relatively low temperatures.

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49
Q

Active site

A

The part of an enzyme molecule into which a substrate molecule fits during a chemical reaction. It’s like a pocket on the surface of the enzyme and it has a specific shape. Only substrate molecule with the complementary shape will be able to fit into this active site.

50
Q

Enzyme - substrate complex

A

Only exists for a fraction of a second until the products are formed. In a chemicial reaction controlled by an enzyme, one or more substrate molecules fit into the active site of the enzyme to form an enzyme-substrate complex. The substrate molecules are held in such away that a reaction takes place.

51
Q

product

A

Each enzyme will catalyse only one specific reaction or type of reaction because only a specific shaped substrate is able to fit into its precisely shaped active site. The complementary substrate binding with the active site is often likened to a “key” which fits into the enzyme’s “lock”.

52
Q

Induced fit theory

A

When the substrate(s) enters the active site, the enzyme molecule changes shape, fitting more closely around the substrate. Only a specific substrate will induce the appropriate change in shape of an enzyme’s active site.

53
Q

How does the 3D structure of proteins enable enzymes to perform their functions as biological catalysts?

A

The globular structure of the protein provides an active site on the surface of the molecule. The complementary substrate molecule(s) fits into he active site and electrically charged groups on the substrate and enzyme molecule surfaces interact. The attraction of oppositely charged groups may distort the shape of the substrate(s) and assist in the breaking of bonds or formation of new bonds, thus catalysing the reaction. Products from that are released from the active site leaving the enzyme uncharged and ready to combine with more substrate molecules. In some cases, the active site may contain amino acids with acidic side chains; the acidic environment created the active site may provide conditions favourable for the reaction.

54
Q

How do enzymes reduce the activation energy?

A
  • Specific shape. Active site and complementary substrate is such that electrically charged groups on their surface interact.
  • Attraction may distort shape of substrate and assist in breaking bonds or forming new ones.
  • Sometimes active sites may contain amino acids with acidic side chains and the acidic environment created within the active site may provide favourable conditions for the reaction.
55
Q

What does intracellular and extracellular reactions mean?

A
Enzymes catalyse many different reaction some, inside cells: Intracellular  reactions (e..g. DNA helicase, DNA perlimarase)
and others in tissue fluid, blood/other aqueous solutions in the organism:
extracellular reactions (eg. digestive enzymes - pensin/amylase)
56
Q

Name 6 facts about enzymes

A
  • Globular proteins
  • Have an active site that allows binding with a specific substrate
  • catalyse (speed up) reactions(intracellular and extracellular)
  • reduce activation energy required for a chem reaction
  • don’t alter the end product/nature reaction
  • don’ get used up and remain unchanged at end of reaction and able to bind with another substrate molecule.
57
Q

What is the general structure of amino acids?

A

All amino acids have the same general structure: their only difference between each one is the nature of the R group. Amino acids consist of an amino group NH2 and a H connected to the central alpha C and a carboxylic acid group and an R group.

58
Q

What is a peptide bond?

A

Forms between the carboxyl group on one amino acid and the amino group on the other amino acid.
Produces water- condensation reaction.
Forms a dipeptide.
When more amino acids are added to a dipeptide, a polypeptide chain is formed.

59
Q

What are and how are
1. Hydrophobic interactions,
2. Disulphides bonds,
Used in proteins?

A
  1. Between non-polar sections of the protein.
  2. One of the strongest and most important type of bond in proteins. Occur between 2 cysteine amino acids.

Hydrogen bonds are also used in all levels of structure.

60
Q

Secondary structure

A
  1. Alpha helix- twisted polypeptide chain forming a helix.
  2. Beta-pleated sheet- parallel chains.
    The structures are maintained by H bonds between C=O and -NH.
    In any one protein there may be regions of both alpha-helices and beta-pleated sheets.
61
Q

Short description of active transport and where it takes place:

A

Energy is required and supplied by ATP (adenosine triphosphate)(an energy transfer molecule). Against conc. gradient low-high. Through carrier proteins that change shape.
E.g.transport ions across epithelial cells, plant cell roots, muscle cells and nerve cells.

62
Q

What do more unsaturated phospholipids do to the fluidity of the membrane?

A

Greater ratio of phospholipids containing unsaturated fatty acids instead of saturated- more fluid membrane will be.
‘Kinks’ in hydrocarbon tails of unsaturated phospholipids prevent them from packing closely. Therefore more movement is possible. Cholesterol site between phospholipids and maintains fluidity of membrane by affecting movement of phospholipids.

63
Q

Factors affecting enzyme concentration:

Enzyme concentration

A

Rate of reaction is directly proportional to enzyme concentration as long as there’s no limiting factors-more active sites available to bind to substrate-substrate limited, more active sites than substrate molecules therefore rate of reaction decreases.

64
Q

Factors affecting enzyme concentration:

Substrate concentration

A

Rate of reaction is directly proportional to substrate concentration until it reaches max value- after a point all active sites will be in use (active site saturation) so increase amount of substrate won’t effect rate of reaction further.

65
Q

Factors affecting enzyme concentration:

pH

A

Most enzymes have narrow optimum pH range.
Most common pH range is similar to amylase-optimum pH 7-8 (neutral) (extremes are rare inside cells).
In v.acidic/ alkaline environments H+/OH- ions interact with amino acids in enzyme breaking bond and altering the shape of active site- causing enzyme to denature.
Pepsin breaks down proteins in stomach (works in extreme pH’s) optimum pH of 1-2.

66
Q

Factors affecting enzyme concentration:

Temperature

A

Temp increases rate of reaction until optimum.
Sub-optimum increase temp=increase KE, therefore reactants move faster-more likely to collide.
Change every 10’C is called temp coefficient (Q10).
Humans optimum temp = around 37’C

67
Q

Why can CF lungs not regulate the water in mucus?

A
  1. CFTR channel is absent or not functional.
  2. Na+ channel is open permanently.
  3. Water is continually removed from mucus by osmosis.
68
Q

What happens when there’s too little water in the mucus?

A
  1. Cl- is pumped into cell across the basal membrane.
  2. Cl- diffuses through the open CFTR channel.
  3. Na+ diffuses down the electrical gradient into the mucus.
  4. Elevated salt concentration in the mucus draws water out of the cell by osmosis.
  5. Water is drawn into the cell by osmosis.
69
Q

What happens when there’s excess water in the mucus?

A
  1. Na+ is actively pumped across the basal membrane.
  2. Na+ diffuses through sodium channels in the apical membrane.
  3. Cl- diffuses down electrical gradient.
  4. Water is drawn out of the cells by osmosis due to high salt concentrations in the tissue fluid.
  5. Water is drawn out of the mucus by osmosis.
70
Q

What is the general structure of amino acids?

A

All amino acids have the same general structure: their only difference between each one is the nature of the R group. Amino acids consist of an amino group NH2 and a H connected to the central alpha C and a carboxylic acid group and an R group.

71
Q

What is a peptide bond?

A

Forms between the carboxyl group on one amino acid and the amino group on the other amino acid.
Produces water- condensation reaction.
Forms a dipeptide.
When more amino acids are added to a dipeptide, a polypeptide chain is formed.

72
Q

What are and how are
1. Hydrophobic interactions,
2. Disulphides bonds,
Used in proteins?

A
  1. Between non-polar sections of the protein.
  2. One of the strongest and most important type of bond in proteins. Occur between 2 cysteine amino acids.

Hydrogen bonds are also used in all levels of structure.

73
Q

Secondary structure

A
  1. Alpha helix- twisted polypeptide chain forming a helix.
  2. Beta-pleated sheet- parallel chains.
    The structures are maintained by H bonds between C=O and -NH.
    In any one protein there may be regions of both alpha-helices and beta-pleated sheets.
74
Q

Short description of active transport and where it takes place:

A

Energy is required and supplied by ATP (adenosine triphosphate)(an energy transfer molecule). Against conc. gradient low-high. Through carrier proteins that change shape.
E.g.transport ions across epithelial cells, plant cell roots, muscle cells and nerve cells.

75
Q

What do more unsaturated phospholipids do to the fluidity of the membrane?

A

Greater ratio of phospholipids containing unsaturated fatty acids instead of saturated- more fluid membrane will be.
‘Kinks’ in hydrocarbon tails of unsaturated phospholipids prevent them from packing closely. Therefore more movement is possible. Cholesterol site between phospholipids and maintains fluidity of membrane by affecting movement of phospholipids.

76
Q

Factors affecting enzyme concentration:

Enzyme concentration

A

Rate of reaction is directly proportional to enzyme concentration as long as there’s no limiting factors-more active sites available to bind to substrate-substrate limited, more active sites than substrate molecules therefore rate of reaction decreases.

77
Q

Factors affecting enzyme concentration:

Substrate concentration

A

Rate of reaction is directly proportional to substrate concentration until it reaches max value- after a point all active sites will be in use (active site saturation) so increase amount of substrate won’t effect rate of reaction further.

78
Q

Factors affecting enzyme concentration:

pH

A

Most enzymes have narrow optimum pH range.
Most common pH range is similar to amylase-optimum pH 7-8 (neutral) (extremes are rare inside cells).
In v.acidic/ alkaline environments H+/OH- ions interact with amino acids in enzyme breaking bond and altering the shape of active site- causing enzyme to denature.
Pepsin breaks down proteins in stomach (works in extreme pH’s) optimum pH of 1-2.

79
Q

Factors affecting enzyme concentration:

Temperature

A

Temp increases rate of reaction until optimum.
Sub-optimum increase temp=increase KE, therefore reactants move faster-more likely to collide.
Change every 10’C is called temp coefficient (Q10).
Humans optimum temp = around 37’C

80
Q

Why can CF lungs not regulate the water in mucus?

A
  1. CFTR channel is absent or not functional.
  2. Na+ channel is open permanently.
  3. Water is continually removed from mucus by osmosis.
81
Q

What happens when there’s too little water in the mucus?

A
  1. Cl- is pumped into cell across the basal membrane.
  2. Cl- diffuses through the open CFTR channel.
  3. Na+ diffuses down the electrical gradient into the mucus.
  4. Elevated salt concentration in the mucus draws water out of the cell by osmosis.
  5. Water is drawn into the cell by osmosis.
82
Q

What happens when there’s excess water in the mucus?

A
  1. Na+ is actively pumped across the basal membrane.
  2. Na+ diffuses through sodium channels in the apical membrane.
  3. Cl- diffuses down electrical gradient.
  4. Water is drawn out of the cells by osmosis due to high salt concentrations in the tissue fluid.
  5. Water is drawn out of the mucus by osmosis.
83
Q

What causes CF?

A

Caused by a mutation in the DNA that carries the instructions for the making CFTR protein.

84
Q

What is a gene?

A

A sequence of bases on a DNA molecule that codes for a sequence of amino acids in a polypeptide chain.
All the genes in an individual or species are known as the genome.

85
Q

Describe the structure of DNA and what it is.

A

DNA is a type of nucleic acid called deoxyribonucleic acid. It’s a long chain polymer made of many units called nucleotides and mononucleotides.
2 polynucleotide strands twisted around each other forming a double helix. 2 sugar-phospahte ‘backbones’ on outside.
Bases point inwards, held together by H bonds.
2 nucleotide strands are described as antiparallel as they run in opposite directions.

86
Q

What is a mononucleotide?

A

Contains 3 molecules linked by condensation reactions. Deoxyribose (5 carbon sugar), phosphate group and an organic base containing nitrogen.
Nitrogen base is only part that’s variable. 4 possibilities: adenine, cytosine, guanine and thymine.
Link together by condensation reactions between sugar of one and phosphate of the next- polynucleotide- phosphodiester bond.

87
Q

Why do the bases pair up A-T and C-G?

A

A and G have a 2 ring structure, C and T have only one ring. They pair to form 3 rings, each rung of the DNA molecule.
Shape and chemical structure determines no. H bonds. A & T have 2 and C & G have 3. A &T and C & G are called complementary base pairs.

88
Q

Where is the CF gene found and what does it do?

A

On chromosome 7.
Long gene of around 230000 base pairs (230kbp).
It instructs the cell to make the CFTR protein that informs the transmembrane chloride channel.

89
Q

What are the 2 stages of protein synthesis?

A

Transcription and translation

90
Q

What is the difference between DNA and RNA?

A

RNA (ribonucleic acid)- single stranded

  • contain ribose sugar instead or deoxyribose sugar.
  • The base Uracil replaces the base thymine.
  • Sometimes a section of the RNA can fold back on itself and complementary base pair with each other- although it appears double stranded it is not.
91
Q

What does RNA polymerase do?

A

The enzyme attaches to the DNA and the hydrogen bonds between paired bases break and the DNA molecule unwinds.

92
Q

How many amino acids are commonly found?

A

20
But there are 64 possible 3 letter combinations.
One triplet is a start code and one is a chain terminator (stop code).

93
Q

Start codon

A

AUG-methionine (complementary code-UAC)

94
Q

Stop codon (chain terminator)

A

UAA, UAG or UGA, no tRNAs with anticodons for these sequences so no amino acids can be transferred- the polypeptide chain stops growing and detaches from the ribosome.

95
Q

What does DNA polymerase do?

A

link the adjacent nucleotides with phosphodiester bonds in condensation reactions to form a new complementary strand.

96
Q

What 3 ways COULD DNA replicate?

A

Fragmentary way (a mixture), SEMI-CONSERVATIVELY (half new, half old) or conservatively (one with 2 new strands, one with 2 old strands).

97
Q

How do we know that DNA replication is semi-conservative?

Matthew Meselson and Franklin Stahl

A

They used heavy and light strands of DNA to distinguish between ‘old’ and ‘new’ strands. They used a bacteria that’d been grown in the heavy isotope of 15^N.
Moved bacteria into normal 14^N- meaning all new strands would be light. Allowed to replicate once then was removed and centrifuged- heavy DNA sinks to bottom-Light at top and medium in middle.
The results showed one band of middle density-so they rejected the conservative idea.
Then let bacteria replicate twice-2 bands- 1 light and 1 medium- therefore DNA replication is semi-conservative.

98
Q

A mutation causes sickle cell anaemia, how?

A

Substitution mutation in gene coding for polypeptide chains in haemoglobin. Base A replaces T at one point along the chain. mRNA produced from this DNA contain triplet code GUA rather than GAA-protein produced contains non-polar, valine instead of polar glutamic acid. This makes the haemoglobin less soluble. When O2 levels are low, molecules form long fibres that stick together inside red blood cell, distorting its shape- results in half moon (sickle) shaped cells carrying less O2 and can block blood vessels.

99
Q

Give some examples of how mutations effect the CFTR protein.

A

-In some cases ATP is unable to bind and open the ion channel.
-In other cases the channel is open but changes in the protein structure lead to reduced movement of chloride ions through the channel.
-Most common mutation- DF508 mutation- is deletion of the three nucleotides- causing loss of phenylalanine, the 508th amino acid in the CFTR protein. Thought to result in misfolding of the protein.
The mutations are passed from parent to offspring.

100
Q

Is the mutated CF gene dominant or recessive?

A

recessive

101
Q

Homozygous genotype

A

there are 2 identical copies of the allele

102
Q

What does a Punnet square do/show?

A

Illustrates all the possible ways in which the 2 types of allele can combine-& thus shows the possible genotypes that could occur in the children.

103
Q

Is there an advantage for Ff (CF carriers)?

A

They have some protection against the dangerous disease, typhoid.

104
Q

Is there an advantage for Ff (CF carriers)?

A

They have some protection against the dangerous disease, typhoid.

105
Q

Example of a condition which is caused by a dominant allele.

A

Achondroplasia (a form of dwarfism).
Huntington’s disease
The ability to taste PTC (bitter-tasting chemical-phenylthiocarbamide)

106
Q

Testing for CF:

Trypsinogen & salt in sweat

A
  • You can test the salt levels in sweat as those with CF have much higher levels.
  • People with CF have much higher levels of tripsinogen in their blood. Testing for this protein is now part of the Newborn Blood Spot Screening Programme for all babies in the UK.
107
Q

Use of Genetic testing/screening to test for CF.

A

Can be performed on any DNA, cheek cells or white blood cells can be taken from a parent and used to find out whether they are a carrier. Embryo or fetus cells can also be tested. The DNA is screened to see if it contains the most common mutation of base sequence.

108
Q

How can genetic screening be used?

A
  • To confirm a diagnosis
  • To identify carriers
  • For testing embryos: Amniocentesis, Chorionic villus sampling and non-invasive prenatal diagnosis (still in early stages)
109
Q

What is amniocentesis?

A

NB. embryo becomes fetus at 10 weeks of pregnancy or 8 weeks after conception.
Amniocentesis is most common method of fetal testing. Involves inserting needle into amniotic fluid to collect fetal cells that have fallen off placenta and fetus.
Amniocentesis is usually carried out at 15-17 weeks of pregnancy, there’s about 1 % of causing a miscarriage.

110
Q

What is Chorionic villus sampling (CVS)?

A

Invasive technique- small sample of placental tissue (which includes cells of the embryo or fetus) is removed, through abdomen or vagina. Carried out at 8-12 weeks no need to wait for amniotic fluid development. 1%- 2% risk of miscarriage- although there’s not much evidence to back this up.

111
Q

What is Non-invasive prenatal diagnosis (NIPD)?

A

Analyses DNA fragments in mother’s blood plama during pregnancy. About 10-20% is from the embryo. Cell-free fetal DNA (cffDNA) becomes detectable in mother at around 4-5 weeks but levels are too low at this stage to be analysed- better at 7-9 weeks.

112
Q

What is pre-implantation genetic diagnosis (PGD)?

A

Couple undergo in vitro fertilisation (IVF), so that embryos can be tested before transfer to the uterus.
At early stages when embryo is growing in culture and has around 8 cells, what can be removed for genetic testing without harming the embryo. Success rates are low ~30% for women under 35.

113
Q

4 widely used ethical frameworks:

A
  1. Rights and duties- right to life, duty to care. religion e.g. 10 commandments, not murdering.
  2. Maximising the amount of good in the world- utilitarianism.
  3. Making decisions for yourself- informed consent.
  4. Leading a virtuous life- virtues e.g. justice
114
Q

What is a genetic counsellor?

A

Someone who explains how a condition is inherited, helps a couple to decide if they want to be tested and provides other general advice on testing and the condition in general.

115
Q

Treating CF:

Medication to relieve symptoms

A
  • Bronchodilators-inhaled using nebuliser-relax muscles in airways, opening them and relieving tightness of chest.
  • Antibiotics- treatment of lung infection.
  • DNAase enzymes- infection leads to more white blood cells in mucus which break down releasing DNA and increase stickiness of mucus. The enzyme is inhaled in nebuliser- breaks down DNA so mucus is easier to clear from lungs.
  • Steroids are used to reduce inflammation of the lungs.
116
Q

Treating CF:

Diet

A

Eat high-energy foods and double the quantity of protein. Possibly salt supplements.

117
Q

Treating CF:

Digestive enzyme supplements

A

If pancreatic duct is blocked, food molecules in small intestine cannot be broken down far enough to be absorbed so enzyme supplements are taken to complete the digestion process.

118
Q

Treating CF:

Physiotherapy

A

Rhythmical tapping of the walls of the chest cavity (percussion therapy) and use of flutter device helps loosen mucus and improve air flow out of lungs. Treatment is carried out regularly, e.g. twice a day.

119
Q

Treating CF:

Heart and lung transplant

A

If lungs become badly damaged and very inefficient, other treatments become ineffective at relieving symptoms. Transplants may be the only option.

120
Q

Treating CF:

Possible CF treatments for the future-gene therapy

A

Use of vectors to carry functional copies to the target cells. This could cure CF by altering the affected cells’ genotypes so functioning CFTR proteins are produced in the epithelial cells. Trials for gene therapy on the CFTR protein are currently in progress.

121
Q

How does preimplantation genetic diagnosis detect CF?

A
  • Ref. to IVF
  • DNA analysed
  • presence of CFTR (gene mutation/ faulty allele)