3.2- Cells Flashcards

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1
Q

What is the cell theory?

A

-All living organisms are made up of one or more cells.

-Cells are the basic functional unit (i.e. the basic unit of structure and organisation) in living organisms.

-New cells are produced from pre-existing cells.

-Cell theory is accepted by ALL scientists!

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2
Q

What is the microscopy equation?

A

magnification= image size/ specimen size

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3
Q

What are the units of measurement for microscopy?

A

metre x 1000 = mm
mm x 1000=micrometre
micrometre x 1000= nanometre

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4
Q

Resolution definition?

A

The minimum distance apart at which 2 seperate objects can be distinguished.

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5
Q

Artefact definition?

A

Something observed that is only there due to preparation techniques- eg air bubbles.

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6
Q

Magnification definition?

A

How much bigger the image is than the original object.

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7
Q

What is an eyepiece graticule?

A

Glass disc with 100 subdivisions, we do not know the length.

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8
Q

What do we do before using an eyepiece graticule?

A

We have to calibrate the graticule as each objective lens will magnify to a different degree so we cannot use the scale directly.

Have to convert graticule units into real units

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9
Q

How do we calibrate an eyepiece graticule?

A

You would use a stage micrometer- another slide which is 1mm and has 100 subdivisions- each division is 0.01mm

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10
Q

So how do we measure the size of a specimen?

A

Line up 1 of the divisions on the eyepiece graticule with a fixed point on the stage micrometer.

Count number of divisions on the eyepiece graticule that correspond with a set measurement on the stage micrometer.

Divide one micrometre measurement (eg 0.1mm) by the n of eyepiece divisions in the same length.

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11
Q

How many µm would each graticule division have if there are 35 divisions in 200µm of the stage micrometer?

A

length of micrometer in µm/ number of divisions

200 µm / 35 graticule divisions = each division is 5.7 µm

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12
Q

What is cell fractionation?

A

A method used to isolate different organelles so they can be studied.

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13
Q

How are the cells prepared?

A

In a cold, isotonic, buffered solution.

Cold- to reduce enzyme activity as when cell breaks open enzymes are released- could damage organelles.

Isotonic- Solution has same water potential as organelles to prevent osmosis as this could cause organelles to shrivel/ burst.

Buffered- solution has pH buffer(stays neutral) to prevent denaturing of the enzyme/protein if the pH were too high or low.

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14
Q

What is 1st step of cell fractionation?

A

Homogenisation.

Cell must be broken open (homogenised) using a blender/ homogeniser. Cells are blended in cold, isotonic, buffered solution.

Solution is then filtered through gauze to remove any large cell/tissue debris.

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15
Q

What is 2nd step of cell fractionation?

A

Ultracentrifugation.

Filtered solution is spun at different speeds in centrifuge, organelles separate according to their densities.

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16
Q

What is process of differential centrifugation?

A

1) Centrifuge spins at lowest speed and centrifugal forces cause organelles to form pellets. Most dense organelles form 1st pellet and move to bottom.

2) Fluid at top of tube (supernatant) is removed, leaving behind the sediment/pellet of the organelle at bottom.

3) Supernatant transferred to another tube and spun in centrifuge at faster speed than before.

4) Process is repeated, with most dense organelle forming sediment, supernatant being spun at faster speed than before.

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17
Q

What is the order that the organelles separate?

A

Nuclei, Chloroplasts, Mitochondria, Lysosomes, Endoplasmic Reticulum, Ribosomes.

(Naughty Chunky Monkeys Like Eating Red Raspberries!)

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18
Q

How does a light microscope work?

A

Light is focused using glass lenses, it relies on the light being able to pass through the specimen.

Regions that absorb more light appear darker in image.

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19
Q

Advantages + disadvantages of light microscope.

A

Advantages- easy to use, cheap, show the true colour of the specimen, can use live specimen.

Disadvantages- low resolution due to longer wavelength of light, low magnification (max 1250X)

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20
Q

2 structures in eukaryotic cell that cannot be identified using an optical microscope?

A

Lysosomes

Ribosomes

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21
Q

What are the 2 types of electron microscope?

A

Scanning Electron Microscope and Transmission Electron Microscope.

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22
Q

How does SEM work?

A

It directs a beam of electrons at a specimen.

It creates an image based on the electrons that are reflected.

It is focused using electromagnets to create a 3D image.

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23
Q

Advantages + disadvantages of SEM?

A

Advantages- much higher resolution than light microscope (1nm), detailed images of surface structures, high mag (300,000X).

Disadvantages- very expensive, extensive training required, samples must be dead (vacuum, stain), false colour/ B+W image.

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24
Q

How does TEM work?

A

It directs a beam of electrons at a specimen.

It creates an image based on the electrons that are absorbed.

It is focused using electromagnets to create a 2D image.

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25
Q

Why can detail not be seen using an optical microscope?

A

Due to the optical microscope using light: light has a longer wavelength so it has a smaller resolution.

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26
Q

Advantages + disadvantages of TEM.

A

Advantages- much higher resolution than light microscope (1nm), detailed images of interior structures, highest magnification (500,000X).

Disadvantages- very expensive, extensive training required, samples must be dead (stain or vacuum), false colour/ black+white image.

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27
Q

Structure and function of cell-surface membrane?

A

partially permeable membrane found on surface of animal cells and some organelles like mitochondria and nucleus.

Mainly made of lipids and proteins-made up of a lipid bilayer, which consists of two layers of phospholipid molecules.

-Regulates movement of substances in and out of the cell

-Has receptor molecules so can easily respond to chemicals like hormones

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28
Q

Structure of the nucleus?

A

Outer nuclear envelope- double membrane which contains pores.

Nuclear pores- control movement of materials between nucleus and cytoplasm

Nucleoplasm- jelly like material which fills the nucleus.

Chromatin- form of DNA found in the nucleus when chromosomes are NOT dividing.

Nucleolus- small spherical body involved in making ribosomes- rNA production. (mini nucleus)

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29
Q

Function of the nucleus?

A

Control centre for cell through the production of proteins

Contains the genetic code for each cell.

Makes ribosomal RNA and ribosomes

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30
Q

Structure and function of mitochondria?

A

Structure- oval shaped, has a double membrane. Inner membrane folded to form cristae (bumpy parts of membrane), matrix inside mitochondria contains enzymes.

Function- site of aerobic respiration(converts energy from food into ATP)

-cristae provides large SA for some enzymes to be embedded into inner membrane

-found in large numbers in metabolically active cells+cells which actively transport.

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31
Q

Structure of chloroplasts (plants+algae)?

A

Has a chloroplast envelope- double plasma membrane which is selective on what can enter/leave the chloroplast.

A stack of disc-like structures called thylakoids- is called a granum. Grana are connected to each other by lamellae.

Fluid filled stroma contains enzymes for photosynthesis.

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32
Q

Function of chloroplasts?

A

1st stage of photosynthesis (light absorption) occurs in grana.
Granal membranes provide large SA- for attachment of chlorophyll, electron carriers, and enzymes that carry out 1st stage of photosynthesis.

2nd stage of photosynthesis ( synthesis of sugars) occurs in the stroma.

Thylakoids contain photosynthetic pigment chlorophyll.

Chloroplasts contain DNA and ribosomes- can easily manufacture some proteins needed for photosynthesis.

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33
Q

Structure of Golgi apparatus+ golgi vesicles?

A

Stack of folded membranes forming cisternae- more curved than ER. Secretory vesicles pinch off from the cisternae.

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34
Q

Functions of Golgi apparatus?

A

-Add carbohydrates to proteins to form glycoproteins

-Produce secretory enzymes

-Secrete carbohydrates (eg- those used in making plant cell wall)

-Transport, modify and store lipids

-Produce lysosomes

-Can label molecules for their destination- eg by adding a receptor

-Transport finished products to cell surface membrane in golgi vesicles where they fuse with membrane and contents are released.

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35
Q

Structure and function of lysomes?

A

Sacs of digestive enzymes formed by golgi apparatus

-Hydrolyse phagocytic cells

-Completely break down dead cells- autolysis

  • Release enzymes to outside of cell to destroy materials- exocytosis

-Digest worn out organelles for reuse of materials.

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36
Q

Structure and function of ribosomes?

A

Small organelles made of 2 subunits- protein and rRNA joined together. 80S- larger ribosomes found in EUKARYOTIC cells. 70S- smaller ribosomes found in PROKARYOTIC cells.

-Site of protein synthesis

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37
Q

Structure and function of rough endoplasmic reticulum (RER)?

A

A 3D system of folded membranes called cisternae.

The cisternae in RER have ribosomes attached.

-The RER folds and packages proteins and sends them to the Golgi Apparatus
-Protein synthesis occurs in RER, provides pathway to transport materials.

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38
Q

Structure and function of smooth endoplasmic reticulum (SER)?

A

A 3D structure of folded membranes called cisternae.

-Synthesises, stores (in sacs), and transports vital lipids and carbohydrates.

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39
Q

Structure and function of cell wall (plants, algae, fungi)?

A

Plants: made of microfibrils of the polymer cellulose.
Fungi: made of chitin, a nitrogen-containing polysaccharide.

Provides structural strength for the cell.

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40
Q

Structure and function of cell vacuole (plants)?

A

Fluid-filled sac surrounded by single membrane called a tonoplast.

-Makes cell turgid by pushing out, providing structural support

-Temporary store of sugars and amino acids

-Pigments may colour petals to attract pollinators

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41
Q

Structure and function of cytoplasm?

A

Contains the organelles, most chemical reactions occur in cytoplasm.

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42
Q

How do prokaryotic cells differ from eukaryotic cells?

A

-They are smaller than eukaryotic cells.
-They have no membrane-bound organelles.
-They have smaller, 70S ribosomes.
-Their cell wall is made of murein (a glycoprotein) not cellulose.
-They have no nucleus- there is a single circular DNA molecule which is free in the cytoplasm.

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43
Q

What extra structures may prokaryotic cells contain?

A

They may also contain: plasmids (small loops of DNA which only contain a few genes) a capsule surrounding the cell to stop the bacteria from drying out (helps to cover antigens on the outside, protects bacteria from immune system, flagella/flagellum which help with movement.

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44
Q

What can plasmids contain?

A

Antibiotic- resistant genes can be found in the plasmids.

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45
Q

What are viruses?

A

Acellular, non living organisms which cannot reproduce independently.

NOT living organisms!!!!!

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46
Q

What is the typical structure of a virus?

A

All viruses contain genetic material (DNA or RNA) which is contained inside a protein structure called a capsid.

On the surface of the virus, there are attachment proteins which allow the virus particle to attach to and enter the host cell.

In some viruses, the capsid can be surrounded by a lipid envelope formed by the host cell membrane.

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47
Q

How may viruses be able to infect other species?

A

A mutation in their viral DNA/RNA could lead to a change in tertiary structure of the viral attachment protein allowing the virus to bind to receptors of other species.

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48
Q

How do viruses reproduce?

A

Viruses cannot reproduce independently, they must reproduce within a host cell.

The virus particle attaches to the surface of a host cell, then it enters the host cell. It uses the host cells enzymes to produce copies of itself. The virus particles leave the host cell and can go on to infect new host cells.

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49
Q

Adaptations of palisade cell in leaf?

A

Large number of chloroplasts: present in cytoplasm to maximise absorption of light for photosynthesis.

Tall + thin shape: allows light to penetrate deeper before encountering another cell wall (cell walls absorb and reflect light), many cells can be densely packed together.

Located right below the epidermis and the cuticle- carries out photosynthesis to produce glucose and oxygen.

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50
Q

Adaptations of root hair cell?

A

Large SA: increases the rate of absorption of water and minerals.

Large permanent vacuole: speeds up movement of water by osmosis from soil across root hair cell.

Many mitochondria: transfer energy needed for active transport of mineral ions into root hair cells.

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51
Q

Adaptations of xylem cell?

A

No organelles or cytoplasm: more space inside vessel for transporting water.

Walls contain pits: allow water and mineral ions to move in and out of the vessel.

Wall contains lignin: strengthens xylem vessel and provides structure+support to the plant.

Dead cells: do not interfere with the mass flow of water.

One way flow system: allows continuous upward flow of water driven by transpiration stream.

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52
Q

Adaptations of phloem cell?

A

Living cells: transport of food through sieve tube elements requires active transport.

Cells are joined end-to-end, contain holes in end cell walls(sieve plates): this forms tubes which allow sugars and amino acids to flow easily through transpiration.

Specialised sieve tubes: have no nuclei, are specialised for transport.

Companion cells: attached to each sieve tube providing the energy for the transport of substances in the phloem- have many mitochondria and ribosomes.

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53
Q

What is gene expression?

A

All cells have same genetic info.

Only a few genes are switched on (expressed) in a given cell.

These are the genes that give the cell its required characteristics.

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54
Q

Organisation of multicellular organisms?

A

cells —> tissues —> organs —> organ systems

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55
Q

What are tissues?

A

Similar cells that are aggregated together (clustered together) to perform a specific function.

These are dependant on one another.

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56
Q

Tissue examples?

A

1) Squamous epithelium tissue- single layer of flat cells lining a surface: found in skin, or alveoli of lung. Selective about which materials can diffuse in or out.

2) Phloem tissue- transports sugar around a plant. Each sieve cell has end walls with holes so sap can easily move through them. End wall = sieve plate

3) Xylem tissue- transports water around the plant, and supports the plant. Contains xylem vessel cells and parenchyma cells.

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57
Q

What are organs?

A

An organ is a structure that contains at least 2 different types of tissue functioning together for a specific purpose.

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58
Q

Organ examples?

A

1) The lungs- made of:
-squamous epithelial tissue which surrounds the alveoli (where gas exchange occurs),
-fibrous connective tissue which contains fibres that help force air back out of lungs when exhaling,
-blood vessels- capillaries which surround the alveoli.

2) The leaf-made of:
-lower epidermis- contains stomata (pores) which let air in or out for gas exchange.
-upper epidermis- covered in waterproof waxy cuticle to reduce water loss.
-spongy mesophyll- space for gas to circulate.
-palisade mesophyll- most photosynthesis occurs here.
-xylem- carries water to the leaf.
-phloem- carries sugar away from the leaf.

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59
Q

What are organ systems?

A

Organs that work together as a single unit to perform a particular function.

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60
Q

Organ system examples?

A

1) Circulatory system- allows transport of gases and other substances around the body. Blood vessels carry blood to tissues, heart pumps blood around body, oxygen from lungs to tissues and organs.

2) Respiratory system- brings O2 into the body and removes CO2. Trachea allows air flow, bronchi carry air into lungs, gas exchange occurs in lungs.

3) Shoot system in plants- includes flowers for sexual reproduction, leaves which are site of photosynthesis, buds which are growing regions and stems for support.

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61
Q

What is the cell cycle?

A

A regular cycle of division separated by cell growth.

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62
Q

What are the 3 stages of the cell cycle?

A

Interphase, Nuclear division and Cytokenisis

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63
Q

What happens during interphase?

A

G1, S and G2.

G1= Gap phase 1: cell grows in size, all organelles are doubled to prepare for the 2 new cells containing the same amount of DNA and being the right size and ATP is produced.

S= Synthesis: The DNA is replicated.

G2= Gap phase 2: cell grows again, DNA replicated is checked for potential mutations (cell is destroyed if there are mutations), proteins needed for division are made, centrioles replicated.

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64
Q

What happens during nuclear division?

A

Mitosis or meiosis: one round of division for mitosis, the cell splits into 2 to produce 2 genetically identical daughter cells.

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65
Q

What happens during cytokenisis?

A

Cell division- the cytoplasm and cell membrane divide to produce 2 new cells (mitosis) or 4 new cells (meiosis).

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66
Q

How is cell division represented on logarithm graphs?

A

You use log when there is a large range of data so it is easier to plot and read.

log(value)

reverse log = 10^log

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67
Q

What are homologous chromosomes?

A

Pair of chromosomes with the same gene loci that determine the same features.

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68
Q

Homologous chromosomes carry the same genes but are not genetically identical- why?

A

They carry different alleles.

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69
Q

What are sister chromatids?

A

2 different copies of the same chromosome held together at the centromere.

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70
Q

How to remember the cell cycle + which part is mitosis?

A

IIIIIIIIIIIIIIPMAT= Interphase, prophase, metaphase, anaphase, telophase.
(PMAT) is mitosis.

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71
Q

What happens during prophase?

A

The chromosomes condense (they become shorter and visible) and the nuclear envelope disintegrates. The centrioles move to opposite poles of the cell and form spindle fibres.

NO NUCLEOLUS

Plants do contain spindle fibres/ apparatus but do NOT have centrioles!

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72
Q

What happens during metaphase?

A

The centrioles are at opposite poles and their spindle fibres attach to the centromere of the sister chromatids.

Chromosomes released from the nucleus line up along the equator of the cell.

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73
Q

What happens during anaphase?

A

The spindle fibres retract back into their centrioles, putting tension on the centromere holding the sister chromatids together.

The centromere divides in 2 and the chromatids are pulled to opposite poles of the cell. This requires energy in the form of ATP provided by respiration in mitochondria. V shape of chromosomes shows that they have been pulled apart at their centromeres.

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74
Q

What happens during telophase?

A

Chromosomes are at opposite poles, becoming long and thin again (CANT SEE THEM).

Spindle fibres disintegrate, nuclear envelope starts reforming around each group of chromosomes.

2 nuclei may be visible.

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75
Q

What happens during cytokenisis?

A

Cell division- the cytoplasm splits to separate the 2 cells, they enter interphase again and the cycle restarts.

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76
Q

Why is mitosis important?

A

For growth of organisms as they increase in the number of cells.

To replace damaged cells which can repair tissue/organs.

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77
Q

What is the mitotic index?

A

The ratio of the number of cells undergoing mitosis to the total number of cells.

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78
Q

How would you calculate mitotic index?

A

number of cells in mitosis (PMAT) /
total number of cells x100

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79
Q

How to calculate how many cells there will be after a certain amount of divisions?

A

2 to the power of however many divisions there are as the number of cells doubles for each cycle.

Eg- 4 divisions= 2^4= 16 cells

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80
Q

In mitosis, what happens to the DNA mass and the chromosome number?

A

The DNA mass halves and the chromosome number stays the same.

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81
Q

What is the role of centromeres in mitosis?

A

They hold sister chromatids together, they attach chromatids to the spindle, allowing the chromatids to move to opposite poles.

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82
Q

Describe appearance and behaviour of chromosomes during mitosis?

A

During prophase chromosomes, condense, shorten and become more visible. Chromosomes appear as two sister chromatids joined at the centromere.
During metaphase chromosomes line up on the equator. Chromosomes are attached to spindle fibres by the centromere. During anaphase the centromere splits and the sister chromatids are pulled to opposite poles of the cell.
During telophase chromatids chromosomes recoil and become longer and thinner.

83
Q

How do prokaryotes divide+ why?

A

Binary fission.

Mitosis is a nuclear division and prokaryotes do not have a nucleus as it is a membrane bound organelle.

84
Q

What is cancer?

A

A disease caused when cells divide uncontrollably and spread into surrounding tissues, it is caused by changes to DNA.

85
Q

How do benign and malignant tumours differ?

A

Benign tumours grow slowly, malignant tumours grow rapidly.

Cells are often well differentiated in benign tumours, cells become de-differentiated in malignant tumours.

In benign tumours, cells produce adhesion molecules which make them stick together and remain in the same tissue, cells in malignant tumours do not produce adhesion molecules so spread to other regions of the body through METASTASIS.

Benign tumours are surrounded by a capsule of dense tissue making them compact, malignant tumours are not surrounded by a capsule so they can grow projections into other tissue.

Malignant tumours are more likely to be life threatening as abnormal tissue replaces healthy tissue.

Benign tumours are usually removed by surgery and rarely reoccur, malignant tumours usually require chemotherapy and/or radiotherapy and may reoccur.

86
Q

What is the cause of cancer?

A

Cancer cells are derived from a single mutant cell.

An initial mutation causes uncontrolled mitosis in this cell.

Later, a further mutation in one of the descendant cells leads to other changes that cause subsequent cells to be different from normal.

87
Q

What are oncogenes?

A

Most are mutations of proto-oncogenes, which stimulate a cell to divide when growth factors attach to a protein receptor on its cell surface membrane.

This activates genes that cause DNA to replicate and cells to divide.

If a proto-oncogene mutates into an oncogene it can become permanently activated.

88
Q

What are tumour-suppressor genes?

A

These have the opposite role to proto-oncogenes.

They slow down cell division, repair mistakes in DNA and tell cells when to die through apoptosis. Normal tumour suppressor genes maintain normal rates of cell division and prevent tumour formation.

If a tumour suppressor gene becomes mutated, it is inactivated and stops inhibiting cell division meaning cells can grow out of control.

Mutated cells are usually structurally and functionally different from normal cells so most die, but some can survive and make clones of themselves forming tumours.

89
Q

Difference between oncogenes and tumour suppressor genes?

A

Oncogenes cause cancer as a result of the activation of proto-oncogenes whereas TSG cause cancer when they are inactivated.

90
Q

Lifestyle factors that can contribute to cancer?

A

-Smoking: danger for smokers and those who passively breathe tobacco smoke in.
-Diet: low-fat, fibre-rich diet, high in fruit and veg can reduce the risk.
-Obesity: being overweight increases the risk.
-Physical activity: those who regularly exercise are at lower risk of some cancers.
-Sunlight: greater exposure to sun/sunbeds= higher risk of sun cancer.

91
Q

What are carcinogens? + examples

A

Any agents that may cause cancer.

Eg- UV light, tar in tobacco, X-rays, some viruses such as oncoviruses can cause cancer so are carcinogens.

92
Q

How may somebody be predisposed to cancer?

A

Everybody has tumour suppressor p53 gene which helps control cell growth: if someone inherits 1 functional copy from their parents, they are predisposed to cancer.

93
Q

How can methotrexate control the rate of mitosis?

A

It inhibits the synthesis stage of DNA nucleotides in cells leading to suppression of inflammation and prevention of cell division.

HOWEVER, it cannot distinguish between cells and can impair non-cancerous cell function and cause long term cell damage.

94
Q

How can vincristine and taxol control the rate of mitosis?

A

They prevent the formation of the mitotic spindle- the chromosomes would not be able to separate and each daughter cell will not receive an identical set of chromosomes so cannot divide.

95
Q

What is chemotherapy?

A

The use of drugs to stop cancer cells from growing, dividing and making more cells.

Cancer cells go through cell cycle faster than normal cells so chemotherapy has a larger effect on the faster growing cells: also can affect healthy fast growing cells such as skin cells or hair follicles.

96
Q

Example of drugs used in chemotherapy?

A

Alkylating agents which damage cell DNA to stop cancer cells from dividing,

Antimetabolites which prevent the cancer cells from making the genetic material they need to create new cells.

97
Q

What is hormone therapy?

A

Cancer treatment that removes, blocks or adds specific hormones to the body.

Used to treat prostate and breast cancer as these use hormones to grow.

98
Q

What is radiotherapy?

A

A method where a beam of high energy particles/ waves (eg- x-rays, gamma rays, electron beams) is directed at cancer cells in order to destroy or damage them.

When the damaged cells die, they are broken down and removed by the body.

Radiotherapy can be combined with chemotherapy.

It can also damage normal healthy cells but these can recover at a faster rate than cancerous cells.

99
Q

Where can radiotherapy not be used?

A

To treat bowel cancer.

100
Q

Which cells can identify non-self cells?

A

Lymphocytes: a type of white blood cell.

101
Q

How do lymphocytes distinguish between pathogens and self cells?

A

Each type of cell has specific molecules on its surface that help identify it. These molecules are usually proteins as their 3D tertiary structure enables lots of identifiable shapes to be made.

102
Q

Which 4 different structures can the lymphocytes identify?

A

1) Pathogens: bacteria, fungi, viruses
2) Cells from other organisms of the same species: this can be harmful for those with organ transplants.
3) Abnormal body cells: such as cancer cells as they make slightly different antigens to self cells.
4) Toxins: some pathogens release toxins into the blood (eg cholera)

103
Q

How do lymphocytes recognise cells?

A

Each of the 10 million lymphocyte types can recognise a different shaped antigen on the cell- surface membrane.

These lymphocytes are made when a person is a foetus, the person is unlikely to be exposed to anything other than self cells.

During development, the lymphocytes complementary to the antigens on self cells will die/ be suppressed- so there are no or very few that are complementary to the own cells to stop them from being attacked.

Remaining lymphocytes are complementary to pathogenic or non-self cells.

This process is still occurring during adulthood- but they are made in the bone marrow.

104
Q

How do pathogens cause disease?

A

Produce toxins- harmful molecules such as botulinum (botox) which stops nerve impulses.
Cell damage- viruses can replicate inside the cells and burst out.

105
Q

What can cause symptoms of autoimmune diseases?

A

If the lymphocytes that are complementary to the antigens on self cells are not destroyed, they can recognise and attack the self cells.

106
Q

What is an antigen?

A

Usually proteins- molecules that generate an immune response by lymphocyte cells when detected on the body.

They are located on the surface of the cell.

107
Q

What is antigen variability?

A

The DNA of pathogens can mutate frequently- if a mutation occurs in the gene which codes for the antigen, then the shape of the antigen will change.

Previous immunity (either natural due to previous infection or artificial through vaccination) will no longer be effective as the memory cells will remember the old antigen shape.

Eg- influenza virus mutates and changes its antigens very quickly so there is a new flu vaccine each year.

108
Q

What triggers an immune response?

A

If a pathogen gets past the chemical and physical barriers (eg- skin and stomach acid) and enters the blood, the white blood cells are the second line of defence.

109
Q

What are the specific and non specific WBC responses?

A

Phagocytes= non-specific

Lymphocytes= specific

110
Q

What is a phagocyte?

A

A macrophage (type of white blood cell) that carries out phagocytosis.

They are found in the blood and in tissues.

111
Q

How is phagocytosis a non-specific response?

A

Any non-self cell (eg- pathogen) that is detected will trigger the same response to destroy it.

112
Q

What are the steps of phagocytosis?

A

1) Phagocytes are within the blood and tissues and any chemicals/debris released by the pathogens/abnormal cells will attract the phagocytes so they move towards the chemicals/debris.
2) There are many receptor binding points on the surface of phagocytes that will attach to chemicals or antigens on the pathogen via the receptors.
3) The phagocyte changes shape to move around and engulf the pathogen.
4) Once engulfed, the pathogen is contained within a phagosome vesicle.
5) A lysosome within the phagocyte will fuse with the phagosome and release its contents.
6) The lysosome enzyme is released into the phagosome- this is a lytic enzyme that can hydrolyse and destroy pathogens.
7) The pathogen is broken down and the soluble products are absorbed and reused by the phagocyte.
8) Antigen is placed on the cell-surface membrane, the phagocyte becomes an antigen-presenting cell.

113
Q

Describe how a phagocyte destroys a pathogen present in the blood (3 marks)

A

The phagocyte engulfs the pathogen forming a phagosome vesicle. This fuses with a lysosome which releases enzymes which hydrolyse the pathogen.

114
Q

What are T lymphocytes ( T cells)?

A

White blood cells involved in the specific immune response: cell-mediated immunity which is immunity involving T cells and body cells.

Made in the bone marrow, but mature in the Thymus gland.

115
Q

What are antigen presenting cells (APC)? +4 examples?

A

Any cell that presents a non-self antigen on their surface. Eg:

-infected body cells will present viral antigens on their surface
-a macrophage which has engulfed and destroyed a pathogen will present the antigens on their surface
-cells of a transplanted organ will have different shaped antigens on their surface compared to self-cell antigens
-cancer cells will have abnormal shaped self-cell antigens

116
Q

What does it mean by cell-mediated response? (CELLULAR= T CELL)

A

The T cells will only respond to antigens presented on cells (APC) and not antigens detached from cells and within bodily fluids such as the blood.

117
Q

What are the steps of the cell-mediated response?

A

1) Once a pathogen has been engulfed and destroyed by a phagocyte, the antigens are positioned on the cell surface. It is now a APC.
2) Helper T cells (type of T lymphocyte) have receptors on the surface which can bind to antigens which are being presented on the antigen-presenting cell.
3) Once attached, this activates the helper T cells to divide by mitosis and replicate to make a large number of clones.
4) The cloned helper T cells differentiate into different cells/stimulate different cells.
5) Some remain helper T cells and activate B lymphocytes, some stimulate macrophages to perform more phagocytosis, some become memory cells for that shaped antigen and some become cytotoxic T cells (killer T cells)

118
Q

How do cytotoxic T cells work?

A

They destroy abnormal or infected cells.

They release a protein-perforin which embeds in the cell surface membrane and makes a pore so any substances can leave or enter the cell, causing cell death.

This is most common in viral infections as viruses infect body cells, the perforin embeds into our own body cells, which are sacrificed to prevent viral replication.

119
Q

What are B lymphocytes (B cells) ?

A

White blood cells which are associated with humoral immunity- involving the antibodies that are present in the body fluids (eg humour)

Made and develop in the Bone marrow

120
Q

Similarities and differences between T cells and B cells?

A

Both a type of white blood cell.

Both involved in the body’s specific defence mechanisms which distinguish between different pathogens to provide immunity.

Both made from stem cells in the bone marrow.

T cells mature in the thymus gland whereas B cells are made and mature in the bone marrow.

T cells are associated with cell-mediated immunity involving body cells whereas B cells are associated with humoral immunity involving antibodies present in body fluids.

121
Q

What does it mean by humoral immunity?

A

Immunity involving B cells producing antibodies that are present in the bodily fluids destroying pathogens.

Antibodies are soluble and transport in bodily fluids. ‘humour’ means bodily fluids= humoral response.

122
Q

How do B-cells work?

A

Antigens in the blood collide with their complementary antibody on a B cell. The B cell takes in the antigen through endocytosis and presents it on its cell-surface membrane.

When this B cell collides with a helper T cell receptor, this activates the B cell to go through clonal expansion and differentiation.

B cells undergo mitosis to make cells which differentiate into memory B cells or plasma cells. A specific B cell is cloned: clonal selection.

123
Q

What is the primary B cell response? primary= plasma

A

B cell antibody binds to viral complimentary antigen. B cells divide by mitosis to make plasma cells. Some divide to form memory cells.
Plasma cells produce specific antibodies to the activating antigen, antibodies attach to antigen on pathogen and destroy it.

124
Q

What is the secondary B cell response?

A

The memory cells circulate in the blood and tissue and they can respond to future infections by the same pathogen by dividing rapidly by mitosis to make antibody producing plasma cells

This is active immunity.

125
Q

Differences between memory cells and plasma cells?

A

Plasma cells produce antibodies, memory cells divide by mitosis and make plasma cells rapidly if they collide with an antigen they have previously seen.

Plasma cells are short-lived, memory cells can live for decades in the body.

126
Q

What is the structure of antibodies?

A

Protein made up of 4 polypeptide chains.

Chains of one pair are long: heavy chains
Chains of another pair are short: light chains

Each antibody has a specific binding site made of a sequence of amino acids that form a specific 3D shape that binds directly to a specific antigen to form an antigen-antibody complex. This binding site is known as the variable region as it is different for each antibody.

Rest of antibody= constant region, binds to receptors on cells.

127
Q

How do antibodies help destroy pathogens?

A

Through agglutination- the antibodies will bind to the antigens to create an antigen-antibody complex. Antibodies are slightly flexible so they can bind to multiple antigens and clump them together.

This makes it easier for phagocytes to locate and destroy the pathogens.

128
Q

What is a monoclonal antibody?

A

Antibodies with the same tertiary structure produced by cloned plasma cells.

129
Q

What are the 2 types of targeted medication related to monoclonal antibodies?

A

Direct monoclonal antibody therapy

Indirect monoclonal antibody therapy

130
Q

What is direct monoclonal antibody therapy?

A

Some cancer can be treated using monoclonal antibodies with a binding site complementary to the antigens on the outside of cancer cells.

The antibodies attach to the cancer cells, whilst they are bound to the cancer antigens other chemicals cannot bind to the cancer cells which would be the cause of uncontrolled cell division.

Monoclonal antibodies prevent the cancer cells from growing and as they only attach to cancer cells, they do not cause harm to other body cells.

131
Q

What is indirect monoclonal antibody therapy?

A

Cancer can be treated with monoclonal antibodies complementary in shape to the antigens on cancer cells which have drugs (cytotoxic drugs) attached to them.

The drugs are delivered directly to the cancer cells and can kill them. Often referred to as bullet drugs.

Reduces the risk of side effects such as those from chemo and radiotherapy.

132
Q

What are the ethical issues with monoclonal antibodies?

A

The production involves innocent animals. Mice are used to produce antibodies and also tumour cells which involves inducing cancer in them, causing most involved in the production of the antibodies to die.

Human testing is also used that can provide a risk of actually having the symptoms of the disease.

There have been deaths related to their use in treating multiple sclerosis.

133
Q

Give examples of what monoclonal antibodies can test for

A

Pregnancy, COVID-19, prostate cancer, influenza, hepatitis, chlamydia.

134
Q

What is immunity? + 2 types.

A

The ability of an organism to resist infection- passive immunity and active immunity.

135
Q

Describe passive immunity

A

This is produced by the introduction of antibodies into individuals from an outside source- the antibodies are not made from their own B cells.

The immunity is short lived as the antibodies are not replaced in the body when they are broken down. Eg- snake anti venom.

136
Q

Describe active immunity

A

This is produced by stimulating the production of antibodies by the individuals own immune system- generally long lasting due to memory cells being created.

137
Q

What is the difference between natural active immunity and artificial active immunity?

A

Natural active immunity is when the person has been infected by the pathogen naturally whereas artificial active immunity is when the immune response is induced in a person, they do not have to suffer the symptoms of the disease (eg vaccines.)

138
Q

What are the differences between passive and active immunity?

A

Active involves memory cells, passive does not.
Active involves production of antibodies by plasma/ memory cells.
Passive involves antibody introduced into the body from an outside source
Active is long term as the antibody is produced in response to a specific antigen,passive is short term as the antibody given is broken down.
Active can take time to develop, passive is fast acting.

139
Q

How are the antigens presented?

A

They are always present in vaccines

They may be free-moving or attached to a dead or weak (attenuated) pathogen

Can be injected or given orally

140
Q

How do vaccines work?

A

The vaccine contains an antigen from the pathogen, a macrophage presents the antigen on its surface. A T cell with a complementary receptor protein binds to the antigen. The T cell stimulates a B cell with the complementary antibody on its surface. The B cell secretes a large amount of the antibody by dividing to produce clones all secreting the same antibody.

141
Q

What would a good vaccination programme look like?

A

1) Herd immunity
2) Economically viable
3) Few side effects
4) Means of producing, storing and transporting the vaccine.

142
Q

What is herd immunity?

A

When a sufficiently large proportion of the vulnerable population have been vaccinated to make it difficult for the pathogen to spread within the population.

143
Q

Why do vaccines not always eliminate diseases?

A

-They fail to induce immunity in those with weak immune systems
-Antigenic variability means pathogens frequently mutate so current vaccines are ineffective
-Individuals may have objections to vaccinations for religious/ethical/medical reasons

144
Q

What are some ethical issues with vaccines?

A

All vaccinations are tested on animals before they can move onto human trials, many people believe this is unethical.

Vaccines may have side effects that can cause long term harm so people may choose not to take some of them- herd immunity cannot occur accurately.

If there is a pandemic such as COVID-19, there may be a struggle between who/ which countries receive the vaccine first, the poorer countries may not be able to afford as many doses of the vaccine as richer countries.

145
Q

What is HIV?

A

Human Immunodeficiency Virus

Belongs to a group of viruses that can make DNA from RNA= retroviruses.

146
Q

What is the structure of HIV?

A

2 strands of RNA are found inside the capsid.

The capsid is the protein in the centre of the HIV molecule, which contains the genetic material and enzymes.

Capsid is enclosed by a viral envelope consisting of a lipid bilayer and glycoproteins: the lipid bilayer is derived from the cell membrane of the T helper cell that the particle escaped from.

Attachment proteins which serve as the first point of contact with the receptor on the cell membrane.

147
Q

How does HIV replicate inside the body?

A

HIV enters the blood stream and circulates the body
Protein on HIV readily binds with a protein on T helper cells called CD4
HIV protein capsid fuses with the cell-surface membrane on T helper cells allowing HIV enzymes (reverse transcriptase and integrase) to enter T helper cells
HIV reverse transcriptase converts the single-stranded RNA from the HIV into double-stranded DNA
The new DNA moves into the nucleus of T helper cells by an enzyme called integrase, creating mRNA
mRNA passes into the cytoplasm and uses ribosomes to make more HIV particles
The new HIV particles coat themselves in T helper cell-surface membrane and break away from cell
Individual is HIV positive

148
Q

Why does HIV negatively affect the body?

A

It reduces the number of T helper cells in the body.

B cells are no longer activated so no antibodies are produced.

This decreases the body’s ability to fight infection which could gradually lead to AIDS

149
Q

What are the effects of reduced T helper cells?

A

-reduced cell-mediated immunity
-reduced activation of B cells so no antibodies made
-reduced cytotoxic cells

150
Q

How does HIV spread between people? + examples

A

Through the direct exchange of bodily fluids.

-sex
-blood donation
-mother to child across the placenta
-mother to child through breast milk

151
Q

Why are antibiotics ineffective against viruses?

A

Antibiotics work by disrupting murein cell wall production, viruses have a protein coat not a cell wall so the antibiotics do not work.

152
Q

How to treat/ reduce symptoms of HIV?

A

HIV uses virus-specific enzymes such as reverse transcriptase.

Antiviral drugs can be designed to target the reverse transcriptase enzyme.

153
Q

What does a DIRECT ELISA test test for?

A

If the persons sample contains the antigens/ hormone.

154
Q

What does an INDIRECT ELISA test test for?

A

The presence of antibodies in a persons sample- this means that the person must also have the antigen as they have created the antibodies.

155
Q

What are the steps to the DIRECT ELISA test?

A

Antibodies complementary in shape to antigens are in bottom of well plate.

Second solution containing second antibody complementary to antigen with an enzyme is added.

The second antibody attaches to the antigen if present and the enzyme causes a change in colour when a colourless substrate is added.

156
Q

How can a DIRECT ELISA test be used for pregnancy?

A

Involves the use of 3 monoclonal antibodies.
1)Mobile antibody is complementary in shape to the hormone/antigen(hCG for pregnancy) being tested for, it has a coloured dye attached to it. Moves along the test strip.
2) Immobilised antibody is also complementary in shape to the hormone/ antigen being tested for, the first antibody stays in this position if the antigen is present.
3) The liquid moves up the test strip again and reaches the last immobilised antibody which is complementary to the first antibody, this binds to the antibody with the colour attached even if the hormone isn’t present: control strip.

157
Q

What are the steps to an INDIRECT ELISA test?

A

Known antigen attached to bottom of well.

Sample from a person supposedly containing antibodies is added, if they are present they attach to the specific antigen.

2nd antibody with enzyme attached is added, binding to 1st antibody.
Colourless substrate is added for the enzyme and if the colour changes, the antibodies are present.

158
Q

What happens before adding the second antibody to direct or indirect ELISA test?

A

The surface must be washed to remove any unbound antigens or antibodies.

159
Q

What is the phospholipid bilayer?

A

2 layers of phospholipid molecules with their hydrophobic tails facing each other and their hydrophilic heads facing outward. The hydrophobic tails mix well with other lipids but repel water, forming a hydrophobic interior, while the hydrophilic heads interact with the surrounding water-based environment as they repel lipids.

Separates watery intracellular fluid (cytoplasm) from watery extracellular fluid-eg- polar molecules cannot pass through non- polar hydrophobic tails.

160
Q

Where are the hydrophobic tails positioned in the bilayer?

A

On the inside of the bilayer

Hydrophobic= non polar

161
Q

What is the role of phospholipids in the cell-surface membrane?

A

They form the bilayer which is a major part of the cell surface membrane.

They allow lipid/soluble substances in or out the cell.

Prevent water soluble substances in or out the cell.

They make the membrane flexible and self sealing.

162
Q

Where are the hydrophilic heads positioned in the bilayer?

A

On the outside of the bilayer

Hydrophilic=polar

163
Q

Why is it called the fluid mosaic model?

A

Fluid: phospholipids and proteins can move around via diffusion, the phospholipids mainly move sideways within their own layers, the different proteins interspersed throughout the bilayer move about within it.

Mosaic: scattered pattern produced by the proteins within the phospholipid bilayer looks like a mosaic when viewed from above.

164
Q

What are the components of a cell surface membrane?

A

Phospholipids, proteins, glycoproteins, cholesterol, glycolipids.

165
Q

What are the 2 types of cell-surface proteins?

A

1- extrinsic proteins (peripheral proteins)
2- intrinsic proteins (integral proteins)

166
Q

What are extrinsic/ peripheral proteins?

A

Proteins that are on the surface or partly embedded into the cell surface membrane.

They provide mechanical support, or are connected to proteins/lipids.
Can be used as receptors for some hormones.

167
Q

What are intrinsic/ integral proteins?

A

Proteins that are within the entire membrane.

Protein carriers/ channel proteins are involved in the transport of molecules across the membrane.

168
Q

What are protein channels?

A

Water filled tubes to allow water soluble ions to diffuse across the membrane.

169
Q

What are carrier proteins?

A

These bind to ions and molecules, then change their shape to move them across the membrane.

170
Q

What are the functions of cholesterol in the cell-surface membrane?

A

-Restricts the lateral (sideways) movement of other molecules in the membrane by providing structural support to the membrane.
-Makes the membrane less fluid at high temperatures: gaps between phospholipids are not too large, this prevents water and dissolved ions leaking out the cell.

171
Q

What are the functions of glycolipids in the cell-surface membrane?

A

-Made of a carbohydrate covalently bonded to a lipid. Carbohydrate extends from bilayer to water environment outside cell.

-Act as recognition sites
-Help maintain stability of membrane
-Help cells attach to one another and form tissues.

172
Q

What are the functions of glycoproteins in the cell-surface membrane?

A

-Carbohydrate chains attached to many extrinsic proteins on the outer surface of cell membrane.

Functions:
1. Act as antigens
2. Involved in identification/recognition of cells - as self/non-self
3. Cell signaling
4. Receptor/binding site for hormones or drugs
5. Receptor/binding site for transport proteins
6. Cell adhesion - hold cells together in a tissue
7. Attach to water molecules (to stabilise membrane)

173
Q

Which molecules can and cannot pass through the partially-permeable membrane by simple diffusion?

A

Can: lipid soluble substances (hormones), small molecules that can diffuse through tiny gaps (CO2, H2O, O2).

Cannot: water soluble substances (eg sodium ions), large molecules (eg glucose).

174
Q

Describe the effect of high temperature on the structure of cell membranes?

A

-Phospholipids have more kinetic energy which increases of gaps between phospholipids
-The bilayer melts and the proteins are denatured.

175
Q

Which factors can increase the rate of diffusion?

A
  • Surface area
  • Concentration gradient
  • Smaller length of diffusion path
176
Q

What is Fick’s Law Equation?

A

diffusion is proportional to…

      length of diffusion path
177
Q

What are the 4 types of transport?

A

Simple diffusion, facilitated diffusion, osmosis, active transport.

178
Q

What is simple diffusion?

A

The net movement of molecules/ ions from an area of higher concentration to an area of lower concentration until equilibrium is reached.

Passive process that does not require ATP: the molecules move to the kinetic energy that they posses which is why this process only occurs in liquids and gases.

Molecules must be small, lipid soluble and non-polar to pass through via simple diffusion.

179
Q

What is facilitated diffusion?

A

Still a passive process as it does not require ATP, just the kinetic energy of the molecules but proteins in the membrane are used to transport molecules.

This is the movement of charged ions, polar molecules and larger molecules like glucose down the concentration gradient from high concentration to low concentration.

180
Q

How do protein channels help with facilitated diffusion?

A

These are proteins embedded all the way through the phospholipid bilayer, the tube fills with water.

Water soluble ions/ molecules can dissolve and pass through the channel, the channel proteins only open in the presence of certain ions when they bind to that protein and change its shape so it is open on one side and closed on the other.

181
Q

How do carrier proteins help with facilitated diffusion?

A

The molecule has to be complementary in shape to the carrier protein, it will bind and that will cause the protein to change shape. The change in shape causes it to release the molecule to the other side on the membrane.

Eg- glucose uses carrier proteins.

182
Q

What is osmosis?

A

The net movement of water from an area of higher water potential to an area of lower water potential through a partially permeable membrane, a passive process.

183
Q

What is water potential?

A

The pressure created by water molecules, measured in kPa and represented by ψ (psi)

Pure water has a water potential of 0, there cannot be a value for water potential higher than 0. When solutes dissolve in the water, the value becomes more negative as the solutes bind to the water molecules lowering their water potential.

184
Q

Which has more solutes dissolved in it,
ψ= -0.5 kPa or ψ= -3.1kPa?

A

ψ= -3.1kPa as this is the more negative value, so the water potential is lower as there are more solutes dissolved.

185
Q

What are the differences between the solute, solvent and solution?

A

Solute= the substance that has dissolved

Solvent= the liquid that has dissolved the solute

Solution= solute and the solvent

186
Q

What is an isotonic solution?

A

When the water potential in the solution and the cell within the solution is the same, water potential on both sides of the membrane is the same.

187
Q

What is a hypotonic solution?

A

When the water potential of a solution is more positive than the cell, it is not a positive value it is a negative value closer to zero.

188
Q

What is a hypertonic solution?

A

When the water potential of a solution is more negative than the cell, it is a more concentrated solution.

189
Q

What would happen if you placed an animal cell in an isotonic solution?

A

There will be no net gain of water, it is at equilibrium as the water potential of the cell and the solution are the same.

190
Q

What would happen if you placed a cell in a hypotonic solution? describe for animal and plant cell.

A

If animal cells are placed in a hypotonic solution, water will move into the cells by osmosis as the outside of the cell is more positive, as animal cells do not have a cell wall they will burst.

If plant cells are placed in a hypotonic solution, water will still move in but they will not burst as they have a strengthened cell wall, so they will become turgid.

191
Q

What would happen if you placed a cell in a hypertonic solution?

A

Both animal and plant cells will shrivel up as the solution outside the cell is more negative so the water will leave the cells by osmosis.

192
Q

What is active transport?

A

The movement of molecules/ ions from a region of lower concentration to a region of higher concentration. Differs from passive forms as ATP is needed, substances are moved against the concentration gradient, carrier protein molecules which act as ‘pumps’ are involved. Very selective as only certain molecules complementary in shape to the carrier proteins.

193
Q

How do carrier proteins assist in active transport?

A

Certain molecules can bind to receptor sites on carrier proteins. ATP binds to the protein on the inside of the membrane, it is hydrolysed into ADP and Pi releasing the energy required for the protein to change shape and open towards the inside of the membrane. The molecule is released on the other side of the membrane. Pi is released from the carrier protein, so the protein reverts back to its original shape.

194
Q

How does direct active transport differ from indirect active transport?

A

Direct- one substance is released on the other side of the membrane whereas with indirect active transport, 1 carrier protein can carry 2 different substances across a membrane, driven by the concentration gradient of one molecule moving against the concentration gradient of another molecule. Does not require ATP.

195
Q

Describe the ileum and epithelial tissues.

A

The ileum surface in the small intestine has small folds called villi. Epithelial cells lining these posses microvilli: finger like projections which increase the SA for the absorption of digestion products through diffusion, and more space for carrier proteins for facilitated diffusion and active transport.

196
Q

Where does absorption occur?

A

From digested chyme (mixture of food in stomach) in the lumen of the ileum through epithelial cells into the blood. Both constantly moving to maintain concentration gradients.

197
Q

Why is active/ co-transport required for glucose and sodium ions in ileum?

A

To absorb glucose from the lumen to the gut, there must be a higher concentration of glucose in the lumen compared to the epithelial cell (for facilitated diffusion to be able to occur)

But, there is usually more glucose in the epithelial cells so co-transport and active transport are required.

198
Q

What are the steps for the co-transport of glucose with sodium ions in the ileum?

A

1) Carrier proteins allow sodium ions to be actively transported out of the epithelial cell into the blood.
2) This reduces the sodium ion concentration in the epithelial cell compared to lumen of ileum.
3) Sodium ions can then diffuse from the lumen down their concentration gradient by facilitated diffusion into the epithelial cell.
4) The protein the sodium ions diffuse through is a co-transporter protein, so 2 different molecules attach before either are transported to the other side.
5) Sodium ions attach to complementary shape receptor, glucose molecules attach meaning the sodium can be released on the other side and glucose can be released against their concentration gradient.
6) High concentration of glucose within epithelial cell enables glucose to move down its concentration gradient from epithelial cell to the blood via facilitated diffusion.

199
Q

Why is the concentration of glucose in the blood lower than the conc in epithelial cells?

A

The blood flows and carries away absorbed glucose.

200
Q

What are the 3 parts of a plant cell?

A

1- central vacuole: solution containing salts, sugars and organic acids

2-protoplast: outer cell surface membrane, nucleus, cytoplasm and vacuole membrane.

3- cellulose cell wall: inelastic covering which is permeable even to large molecules.

201
Q

What occurs to a plant cell when it is placed in a solution of higher water potential (HYPOTONIC)?

A

water enters cell by osmosis, the protoplast swells and is pushed against the cell wall. The cell is turgid.

202
Q

What occurs to a plant cell when it is placed into a solution of equal water potential (ISOTONIC) ?

A

No net movement of water, there is no change to the protoplast. The cell has undergone incipient plasmolysis, the protoplast begins to push away from the cell wall.

203
Q

What occurs to a plant cell in a solution of lower water potential (HYPERTONIC)?

A

The water leaves the cell, the protoplast shrinks. The cell has plasmolysed as the protoplast has completely pushed away from the cell wall. Cell death occurs