All lectures

Question 1

What are the 4 pathological processes constantly stressing aerobic organisms?

Answer 1

1) Reactive O2 species - mainly of cellular origin
2) DNA damaging electrophiles/carcinogens - from environment and damage
3) Inflammation/infection
4) Radiation

Question 2

What are 4 robust cytoprotective systems?

Answer 2

1) Small molecule direct antioxidants e.g glutathione, ascorbate
2) Housekeeping antioxidant enzymes e.g. superoxide dismutases, catalase
3) DNA damage repair systems
4) Inducible cytoprotective enzymes e.g. the Keap1-Nrf2 pathway

Question 3

What is Azathioprine?

Answer 3

A thiopurine. A highly effective anti-inflammatory and immunosuppressive agent. Widely used in organ transplant, autoimmune diseases and inflammatory bowel diseases.

Question 4

Epigenetic - Definition?

Answer 4

The study of changes in an organism caused by modification of gene expression rather than the alteration of the genetic code itself

Question 5

What are chromocentres?

Answer 5

Portions of chromosome that remain in a condensed state throughout the cell cycle (even in interphase)

Question 6

What is the Histone code?

Answer 6

The hypothesis that the transcription of genetic information encoded in DNA is in part regulated by chemical modifications to histone proteins, primarily on their unstructured ends

Question 7

For a chemical compound to make it to market, they must posses these 4 qualities.

Answer 7

ADME.

Absorption
Distribution
Metabolism
Excretion

Plus efficacy.

Question 8

What are the reactions involved in Phase 1 metabolism (Modification) ?

Answer 8

• Oxidation
• Reduction
• Demethylation
• Hydrolysis
• Decyclisation

Question 9

What are the reactions involved in phase 2 metabolism (Conjugation)

Answer 9

• Methylation
• Sulphation
• Acetylation
• Glucuronidation
• Glutathionylation
• Glycination

Question 10

What is functional action of Flavin-containing monooxygenase (FMO)?

Answer 10

Responsible for N and S oxidation.

Example;
Trimethylaminuria (TMA) -> TMA N-oxide

Question 11

What are the action of Cytochrome p450s ?

Answer 11

They are enzymes which function to metabolised potentially toxic compounds/ drugs.

4 Families.

CYP1: PAHs
CYP2: Many Drugs
CYP3: Oxidises around 50% of clinical drugs
CYP3: “Peroxisome proliferators”

80% of drugs are metabolised by p450s.

Question 12

What are the 4 stages of Transcription?

Answer 12

1. Template recognition
2. Initiation
3. Elongation
4. Termination

Question 13

What are the 5 ways in which target cells can become desensitised to a signal molecule?

Answer 13

1. Receptor Sequestrion
2. Receptor Down-Regulation
3. Receptor Inactivation
4. Inactivation of Signalling Protein
5. Production of Inhibitory Protein

Question 14

What is a stem cell?

Answer 14

A cell which can self-renew and differentiate

Question 15

What are PTMs?

Answer 15

They are covalent additions introduced to amino acids, post-translationally. Which change the physiochemical properties of the modified residue.

Question 16

What can PTMs end up modulating?

Answer 16

• Activity
• Localisation
• Stability
• DNA/RNA - binding
• Complex formation
• Selectivity

Question 17

What is the action of MPS1?

Answer 17

MPS1 localises to a kinetochore. Here it recruits other proteins and assembles then into an inhibitory complex (MCC)

Competition exists between MPS1 and microtubules

Question 18

Aneuploidy and Tetraploidy?

Answer 18

Abnormal number of chromosomes

And

Double the chromosome content (usually due to cytokine failure)

Question 19

4 stages of Darwin’s style tumour evolution.

Answer 19

1. Confined
2. Diffuse
3. Metastasis
4. Recurrence

Question 20

What do circulating Mfg-E8 and annexin 1 do?

Answer 20

Bind to phosphatidylserine and acts as targets for macrophages.
Promotes PM scrambling during apoptosis.