NORMAL CELL REVISION

Question 1

What are examples of signalling molecules?

Answer 1

• growth factors
• hormones
• cytokines
• neurotransmitters

Question 2

What are growth factors

Answer 2

signalling molecules that after binding to growth factor receptors signal cells to grow and proliferate

Question 3

What are the 3 steps of signalling?

Answer 3

1. reception
2. transduction
   - single-transduction pathway
3. response
   - activation of cellular responses

Question 4

What are protein kinases?

Answer 4

Enzymes that transfer phosphate groups to substrates that contain serine, threonine or tyrosine residues
Protein kinases can be tyrosine kinase (e.g. EGFR, VEGFR) or serine/threonine kinase (e.g. CDK)
Kinases can be cell-surface receptor kinases (e.g. EGFR) or intracellular receptor kinases (e.g. JAK)

Question 5

What are tyrosine kinases and what do they do?

Answer 5

They selectively phosphorylate tyrosine residues in proteins
Phosphorylate: transfer a phosphate group from ATP to tyrosine residues
This activates inactive cells (“on-off switch”)
Receptor tyrosine kinases are activated by ligand binding to extracellular domain
Binding of growth factor switches tyrosine kinase ‘on’–> signals cell to divide

Question 6

What is the DNA structure

Answer 6

Double helix of 2 complementary strands
Composed of nucleotides:
Sugar (deoxyribose)
Phosphate group
Nitrogenous bases (Adenine, Thymine, Guanine, Cytosine)
Pyrimidines: Cytosine & Thymine
Purines: Adenine & Guanine
Hydrogen bonds between bases on opposite strands
G-C base pairs have 3 hydrogen bonds
A-T base pairs have 2 hydrogen bonds

Question 7

What does topoisomerase do?

Answer 7

unwind & rewind DNA strands to prevent DNA getting tangled (supercoiling)

Question 8

What does telomerase do?

Answer 8

adds telomeres (protective end caps of chromosomes) at DNA 3’ ends
Without telomeres, the chromosomes will be prone to genomic instability & degradation
Cancer can upregulate telomerase, giving the cancerous cells a survival advantage

Question 9

What do telomeres do?

Answer 9

(TTAGGG repeats) protects DNA from progressive degradation
Are repeated hundreds or thousands of times
Steady shortening of telomeres with each replication in somatic cells has a role in senescence (state of permanent cell cycle arrest)

Question 10

What is the G1?

Answer 10

growth phase: increase in size, cellular contents duplicated

Question 11

S phase?

Answer 11

DNA replication

Question 12

G2 phase?

Answer 12

more growth, organelles & proteins developed (preparation for cell division)

Question 13

M phase?

Answer 13

mitotic phase: mitotic divison and cytokinesis -> 2 daughter cells

Question 14

what is the G0 phase?

Answer 14

resting phase - growth arrest (quiescence or senescence)

Question 15

What are the cell cycle regulators

Answer 15

Positive & negative regulatory events (phosphorylation/dephosphorylation) involve:
Protein kinases
Protein phosphatases (remove phosphate groups)
Cyclins
Cyclin-dependent kinases (CDKs)
Cyclin-dependent kinase inhibitors (CDKIs)

Question 16

What do cyclins do?

Answer 16

activate cyclin dependent kinases (CDK)
without cyclins, CDK’s have no activity

Question 17

What do CDK’s do

Answer 17

-phosphorylate (to activate or inactivate) proteins on serine or threonine residues
-CDKI’s inhibit the activity of CDK/cyclin complexes

Question 18

What is the purpose of cell cycle checkpoints?

Answer 18

Progression through each phase is monitored by cell cycle checkpoints
Unreplicated, mutated or damaged DNA blocks progression of cell cycle at checkpoints
Cell cycle can progress unchecked–> further mutations–> cancer
- G1 checkpoint - cell growth checkpoint
- S checkpoint - DNA synthesis checkpoint
- M checkpoint - mitosis checkpoint

Question 19

What are the steps of mitosis and what is mitosis

Answer 19

2 identical daughter cells are generated
1, prophase
2. prometaphase
3. metaphase
4. anaphase
5. telophase &cytokinesis

Question 20

Explain the steps of prophase

Answer 20

1. Prophase: sister chromatids condense, mitotic spindle begins to form, centromeres more to opposite poles of cell

Question 21

What are the steps of pro metaphase?

Answer 21

the nuclear membrane breaks down, spindles fibres attach to centromeres of sister chromatids at the kinetochore

Question 22

What is metaphase

Answer 22

spindle fibres align chromosomes along the equator

Question 23

What is anaphase

Answer 23

sister chromatids separate
- spindle fibers pull chromosomes toward oposite poles
- chromosomes segregate at opposite poles

Question 24

What is telophase & cytokinesis

Answer 24

mitotic spindle breaks down
- new nucleus forms around chromosomes at each pole
- cleavage furrow forms
- cytokinesis occurs, pinching cell of into two new daughter cells

Question 25

Aerobic respiration?

Answer 25

glycolysis : - cytoplasm, glucose into 2 pyruvate, generates net of 2 ATP mitochondria - pyruvate undergoes oxidative phosphrylation& will produce approx. 32 ATP molecules, in addition to the 2 molecules produced by glycolysis aerobic metabolism: Acetyl-CoA feeds into TCA cycle & then oxidative phosphorylation Produces approx. 34 molecules of ATP, plus CO2 & H2O waste Needs O2

Question 26

Anaerobic conditions?

Answer 26

- glycolysis - Lactate fermentation 2 ATP molecules that were produced previously from glycolysis Oxidative phosphorylation produces lots of energy When no oxygen present, pyruvate fermented to lactate Lactate is transported to liver for gluconeogenesis No extra ATP

Question 27

What are the example forms of programmed cell death

Answer 27

Apoptosis (type I) autophagy (type II)

Question 28

What is necrosis

Answer 28

non-physiological process due to infection or injury

Question 29

What are the steps of apoptosis

Answer 29

1. Cytoplasmic shrinkage 2. Chromatin condensation 3. Nuclear fragmentation 4. Plasma membrane blebbing & formation of vesicles (apoptotic bodies) 5. Apoptotic bodies taken up by phagocytic cells & degraded in lysosomes Doesn’t cause inflammation

Question 30

What are the two major pathways of apoptosis

Answer 30

Intrinsic (or mitochondrial): due to internal stress signals (DNA damage, oxidative stress) Extrinsic: due to extracellular cues detected by death receptors Apoptotic machinery is composed of upstream regulators & downstream initiators & effectors (caspases: intracellular proteases)

Question 31

What are the steps of extrinsic apoptosis?

Answer 31

1. Extracellular death-inducing signals received by death receptors (FAS & TRAIL-R) 2. Caspase-8 (or 10) is activated 3. Effector caspases (caspase 3) are activated & execute the death programme

Question 32

What are the steps of intrinsic apoptosis

Answer 32

1. BH3-only molecules sense intracellular signals 2. Proapoptotic proteins (Bax, Bak) permeabilise mitochondria membranes to allow cytochrome C release 3. Cytochrome C release activates caspase-9 4. SMAC is also released 5. Effector caspases (caspase-3) are activated & execute the death programme

Question 33

What are the steps of inhibitory signalling of apoptosis

Answer 33

1. Antiapoptotic Bcl-2 proteins (Bcl-2, Bcl-XL) block cytochrome C release from mitochondria 2. Inhibitors of apoptosis (IAP) proteins inhibit effector caspases 3. SMAC inhibits IAPs allowing apoptosis to happen

Question 34

What is autophagy?

Answer 34

cells eat themselves up and recycle products

Question 35

How does autophagy-microphological changes occur?

Answer 35

-Extensive cytoplasmic vacuolization -Intracellular vesicles (autophagosomes) envelope organelles -Fuse with lysosomes -Lysosomal degradation Enables break down of cellular organelles (ribosomes, mitochondria)--> recycled products used for biosynthesis & energy metabolism

Question 36

What are the steps of necrosis

Answer 36

Cell digestion due to infection or injury Cell swelling Membrane disruption Disposal of cell corpses without phagocytic & lysosomal involvement Inflammatory response