GI Dysfunction Flashcards

(62 cards)

1
Q

What is p53?

A

A transcription factor
Regulates G1/S checkpoint by preventing progression into S phase when the environment is not favourable
Tumour suppressor gene

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2
Q

What happens to p53 when the environment is favourable for cell proliferation?

A

p53 is ubiquitylated by mdm2 and undergoes proteasomal degradation

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3
Q

What happens to p53 when the environment is NOT favourable for cell proliferation?

A

DNA damage causes p53 phosphorylation to protect it from ubiquitylation
p53 transcribes genes including p21
p21 inhibits CDK4 and CDK6

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4
Q

What does Retinoblastoma do under normal conditions?

A

Binds to/Inhibits the E2F transcription factor

Prevents transcription of E2F controlled genes that are required for cell cycle progression into S phase

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5
Q

What are cyclins and what do they do?

A

Cyclins are proteins that regulate the cell cycle
Different cyclins are present at different times during the cell cycle
Needed to activate cyclin dependent kinases

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6
Q

What are CDKs?

A

Cyclin dependent kinases

Phosphorylate targets within cell, allowing progression past a checkpoint

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7
Q

How is Retinoblastoma inhibited?

A

It becomes phosphorylated by CDK4 and CDK6

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8
Q

What is glycogenolysis?

A

Glycogen breaks down to form glycogen and glucose-6-phosphate
Sequential removal of monomers
Catalysed by glycogen phosphorylase

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9
Q

What is the name of the reaction taking place during glyogenolysis?

A

Phosphorolysis

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10
Q

How is glucose used to generate ATP?

A

Glucose undergoes glycolysis to produce pyruvate
Pryruvate enters the citric acid cycle in a mitochondria
Reduced products undergo oxidative phosphorylation in the electron transport chain

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11
Q

Where does glycogenolysis takes place?

A

Muscle cells and liver cells

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12
Q

What is gluconeogenesis?

A

Glucose is created from sources other than glycogen e.g. glycerol and amino acids

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13
Q

What is insulin?

A

Peptide hormone release by beta cells of the pancreas in response to high blood glucose

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14
Q

What downstream effects does insulin have?

A

Upregulates insertion of GLUT4 transporter into the membrane of adipose and muscle cells (and liver???)
WHAT ELSE

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15
Q

What is glucagon?

A

Peptide hormone released by alpha cells of the pancreas in response to low blood sugar

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16
Q

What downstream effects does glucagon have?

A

Upregulates glycogenolysis

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17
Q

What do GLUT transporters do?

A

Facilitates transport of glucose across cell membranes using the glucose concentration gradient, via conformational change

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18
Q

How many types of GLUT transporters are there?

A

14

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19
Q

What are the main GLUT transporters and where are they found?

A

GLUT 1 and GLUT 3 - most cells
GLUT 2 - liver and pancreas
GLUT 4 - adipose cells, skeletal and cardiac muscle

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20
Q

Where does absorption of nutrients take place?

A

Small intestine: duodenum (90%), jejenum and ileum

Large intestine: water and >10% nutrients

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21
Q

How are the different nutrients absorbed?

A

Carbohydrates (glucose, fructose, galactose) and amino acids are absorbed by cotransportation with sodium
Fats are absorbed with passive diffusion as they are lipophilic
All vitamines absorbed by passive diffusion

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22
Q

What are the possible ligands of the insulin receptor?

A

Insulin, IGF-1, IGF-2

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23
Q

What two signalling pathways are initiated by the insulin receptor?

A

MAPK cascade and PI3K

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24
Q

What two signalling pathways are initiated by the insulin receptor?

A

MAPK cascade and PI3K

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25
Describe the MAPK cascade
1. Ligand binds to insulin receptor 2. Dimerisation and trans-autophosphorylation 3. Attracts SH2 domain on Grb2 4. Grb2 brings SOS 5. SOS converts GDP on Ras to GTP 6. Ras activates Raf 7. Raf phosphorylates MEK 8. MEK phosphorylates ERK 9. ERK translocates to the nucleus to transcribe genes
26
What happens in each stage of the cell cycle?
``` G0 - cell cycle arrest G1 - Replication of everything except DNA S - DNA replication G2 - Preparation for division M - mitosis ```
27
What is checked at each cell cycle checkpoint?
G1/S - Is the environment favourable? | G1/M - Is all DNA replicated? Are all DNA errors corrected?
28
What is a mitogen?
Substance that stimulate cell proliferation e.g. Insulin, EGF, VEGF, TGF-a
29
Which checkpoint is mitogen dependent?
G1/S
30
What is retinoblastoma?
Tumour suppressor protein
31
What is APC (disease)?
Adenomatous Polyposis Coli | Form of colorectal cancer
32
What is the cause of APC?
A mutation in the APC gene No functioning destruction complex No destruction of beta catenin Uncontrolled cell proliferation
33
What is beta catenin?
Transcription factor | Involved in the Wnt signalling pathway
34
Describe the Wnt signalling pathway
Wnt binds to it's receptor, Frizzled This activates the intracellular Dishevelled protein Dishevelled inhibits the GSK kinase in the beta-catenin destruction complex No destruction Beta catenin transcribes genes Cell proliferation
35
What is APC (protein) and what does it do?
APC is a protein in the beta-catenin destruction complex Forms complex with a GSK kinase and actin Phosphorylates beta-catenin, marking it for ubiquitylation and proteasomal degredation
36
What is DCC?
The 'deleted in colorectal cancer' gene Codes for a receptor present on the villi in the small intestine Acts as a tumour suppressor gene AND oncogene, depending on whether the ligand is bound or not
37
What is the function of DCC when the ligand is bound?
Netrin-1 binds DCC stimulates MAPK cascade Results in cell proliferation
38
What is the function of DCC when the ligand is not bound?
No Netrin-1 bound | DCC stimulates apoptosis of the cell
39
What is the cause of DCC?
A mutation in the gene for DCC No functioning receptor to stimulate apoptosis No suppression of growth
40
How does DCC result in formation of villi?
Netrin-1 is present at the base of the villi, stimulating cell proliferation Netrin-1 is absent at the tip of the villi, so DCC stimulate apoptosis here
41
Symptoms of diabetes
Polyuria Increased thirst Increased hunger Changes in vision as glucose is absorbed by the lens of the eye
42
What is the cause of Type 1 diabetes?
Autoimmune destruction of beta pancreatic cells that produce insulin Insulin-dependent
43
What is the cause of Type 2 diabetes?
Cells become resistant to insulin, and less insulin is produced Linked to obesity and lack of exercise
44
2 possible treatments for diabetes
Insulin injections | Metformin - suppresses gluconeogenesis, to decrease glucose production
45
What is recombinant DNA?
DNA that has been made by putting DNA from multiple different organisms together
46
What are biologics?
Drugs that have been manufactured from living systems | Includes recombinant DNA and monoclonal antibodies
47
What are monoclonal antibodies?
Antibodies generated by injecting an organism with the target antigen, so their adaptive immune system creates antibodies
48
Uses of monoclonal antibodies
1. Bind to and block receptors involved in cell proliferation e.g. HER2 2. Bind to and block IL-2 receptors on T cells to prevent activation, to suppress the immune system. Useful for preventing organ rejection following transplant 3. Antibody can be conjugated to a radioactive molecule and targeted to cancer cells, to kill the cells
49
How are monoclonal antibodies made?
1. Inject organism with target antigen via intraperitoneal injection 2. Organisms spleen cells produce antibodies 3. Extract spleen cells and fuse them with myeloma cells to create hybridomas 4. Hybridomas produce monoclonal antibodies
50
How can you test if an organism is producing antibodies?
Use a test bleed to test if antibodies have been produced
51
How do you screen hybridomas to check that they have fused correctly?
Grow them on HAT medium | Non fused spleen/myeloma cells die
52
What are first generation monoclonal antibodies?
Antibodies that have been extracted from a non-genetically modified organism
53
What are second generation monoclonal antibodies?
The organism has been genetically modified before injecting with antigen This enables creation of chimeric or humanised mAbs
54
What are chimeric mAbs?
The Fc region of the antibody is human but the Fab region is not
55
What are humanised mAbs?
Majority of the antibody is human
56
How is recombinant DNA created?
Host plasmid cleaved using restriction enzymes Creates sticky ends Annealing of new gene (e.g. insulin gene) into plasmid Forms recombinant plasmid
57
Uses of recombinant DNA
Recombinant plasmid inserted into bacteria Bacteria produces protein Can be used to make insulin and glucagon
58
What is the structure of an antibody?
``` 2 long heavy chains 2 short light chains Chains connected by disulfide bond Fab region (antigen binding) Fc region ```
59
What is the difference between monoclonal and polyclonal antibodies?
``` Monoclonal = one species of antibody, produced by identical immune cells Polyclonal = mixture of antibodies, produced by several types of plasma cells ```
60
Pros/Cons of humanised antibodies
Pros: Less likely to cause immune reaction, Longer half life Cons: Takes longer to develop, More expensive
61
What is parenteral administration?
Any systemic form of administration that is not through the GI tract
62
What is the two functions of IL-2?
Proliferation of T cells | Activates JAK/STAT receptors