The Patient - Sem1 Flashcards
1
Q
Describe the timeline of life origins on Earth
A
- Prokaryotes were first cells (3.7bil years before humans)
- Eukaryotic were first cells with a nucleus (2.5bil years before humans)
- Oxygen atmosphere formed 1.5-2bil years before humans
- Multicellular organisms
- Dinosaurs
- Humans
2
Q
What is the Cell Theory?
A
- All living things made of cells
- Cells formed from existing cells
- Organisms may consist of one or many cells
3
Q
How was the Cell Theory proved?
A
- Louis Pasteur
- Broth in curved neck flask - No microorganism growth exhibited as no cells come into contact with broth
- Curved neck removed - Microorganisms can enter and grow through cell division
4
Q
What are the basic features of all cells?
A
M - Always a selective outer MEMBRANE present, inner membranes may also be present
N - Genetic material is made of NUCLEIC ACIDS, inherited from parent cell or moved between cells
M - METABOLISM includes all the processes that occur in a cell that are critical to its survival
M - MOTILITY of the cell or it’s individual components is key to its survival and metabolism
5
Q
What are the key difference between prokaryotes and eukaryotes?
A
- SIZE: E. 10-100mcm, P. 1-5mcm
- Prokaryotes have no nucleus/membrane bound organelles/cytoskeleton
- METABOLISM: E. respiration or photosynthesis, P. varied metabolism
- CHROMOSOMES: E. many, linear chromosomes, P. single, circular chromosome
- Cell wall present in most prokaryotes but only plant and fungi eukaryotes
- E. generally multicellular, P. usually unicellular
- P. move using simple flagella, E. have complex microtubule flagella
- P. smaller ribosomes
- E. Cell division by mitosis/meiosis, P. division by binary fission
6
Q
How do the size and shape of cells vary?
A
- Max. size dependent on SA:V ratio, big ratio causes problems with material exchange
- Cell needs to be big enough to carry out all metabolic functions
- Cell size varies from about 1mcm-1mm
- Organelle size varies from 1-10mcm
- Shape of cell may vary depending on function
7
Q
Why do drugs have to cross a number of membranes in the body?
A
- Drugs enter bloodstream to reach target tissues (unless used topically)
- Unless injected drugs must cross many epithelial membranes to reach bloodstream and then target tissues
- May have to cross cell membrane if action is in cell
8
Q
What are the common features of a typical membrane, and what is its arrangement?
A
- “Sheet-like” boundaries
- Lipid bilayers spontaneously formed
- Asymmetric
- Fluid - Dependent on saturation of fatty acids (C=C)
- Non-covalent
- Specific proteins in membrane determine function
- 6-10nm thick
9
Q
Describe the structure of phospholipids
A
- Lipid + phosphate group
- Glycerol or sphingosine backbones
- Phosphoglycerides - fatty acid tails and phosphate+alcohol head attached to glycerol backbone
10
Q
Describe the structure and function of fatty acids
A
- Straight carboxylic acid chains
- Unsaturated chains causes membrane fluidity (not packed together as closely)
- Can be stored as triglycerides and then used to produce ATP
- Can be used to make a specific target molecule
- Intracellar messengers (Eicosanoid family) - Oxygenated 20C f. acids
11
Q
Describe the structure of glycolipids
A
- Lipid + sugar group
- Sphingosine backbone, one fatty acid and one or more sugar groups
- Fatty acid bonded to NH3+ group and sugar usually bonded to hydroxyl group
12
Q
Describe the structure and function of cholesterol
A
- Sterol (Steroid Alcohol) - Polar -OH group and hydrophobic rings/chains
- Only found in animal cell membranes - regulate membrane fluidity bit fitting between f. acid molecules
- Prevents transition of fatty acids from gel to fluid
13
Q
Why do lipid bilayers form spontaneously?
A
- Amphipathic molecules (phospholipids)
- In aqueous conditions bilayer forms to exclude water from hydrophobic region
- Liposomes can form from bilayers
- Bilayers are more energetically favoured than monolayers
14
Q
What is the relationship between the permeability coefficient and the ability to traverse lipid bilayers?
A
- Coefficient represents solubility in organic solvents compared to solubility in water
- Bigger coefficient = more easily passes bilayer
15
Q
How does the protein:lipid content in membranes vary?
A
- Varies depending on function of membrane
- If a lot of transport is required (e.g. liver) protein content may be high
- If membrane has an insulation function protein content may be low
16
Q
What are integral proteins?
A
- Embedded in the membrane, usually span the entire membrane
- Usually alpha-helical structures
17
Q
What are peripheral proteins?
A
- Loosely associated with membranes
- Cytosolic or extracellular
18
Q
How are membranes synthesised?
A
- Growth of existing membranes
19
Q
What is an animal cell glycocalyx?
A
- Layer of carbohydrates on extracellular surface
- May be attached
- Stained with ruthenium red
- Functions: cellular recognition and adhesion, disease development (pathogenesis)
- Made glycolipids and proteins and proteoglycans
- Membrane sugars are involved in cellular communication
20
Q
Give an example of a drug that blocks membrane transport
A
- Digitalis (from foxglove leaves)
- Treatment of heart disease
- Prevents ion transport across membranes of cardiac muscle cells
21
Q
Give an example of a disease where MDR transporters cause drug resistance to develop
A
- Cancer - over expressions of MDRs causes removal of anti-cancer drugs. Causes resistance to a number of drugs at the same time
- Malaria - Parasites resistant to anti malarial due to expression of MDRs
22
Q
What are multi drug transporters?
A
- Pump a number of drugs out of cells, reducing their efficacy
23
Q
What is endocytosis?
A
- Large molecules moved into cell by vesicles
- Pinocytosis - bulk transport of liquids into the cell
- Phagocytosis - bulk transport of solids into the cell
24
Q
What is exocytosis?
A
- Movement of large molecules out of the cell using vesicles
- Constitutive = continuous movement
- Regulated = movement triggered by receptors
25
What is simple diffusion?
- The movement of small molecules down a concentration gradient through a partially permeable membrane
- Gasses and small polar molecules can pass through membrane
26
What is facilitated diffusion?
- The movement of small molecules down a concentration gradient through proteins embedded in the membrane
- Faster than simple diffusion
27
What is active transport?
- The movement of small molecules across a membrane using energy from ATP, movement is against the concentration gradient
28
What are the types of simultaneous transport of molecules?
- Symport carrier proteins - Simultaneous transport of molecules in the same direction
- Antiport carrier proteins - Simultaneous transport of molecules in opposite directions
29
What are the types of proteins used in facilitated diffusion?
- Channel proteins - Water filled pores that allow ion transport
- Carrier proteins - Changes shape when solute binds (much slower than channel)
30
What is saturation in terms of facilitated diffusion?
- Saturation occurs when all transporters are being used
31
What are the two types of transport proteins used in active transport and what are their structures? Give an example of each
- P-class transporters: Alpha unit to bind to substrate, unit below accepts phosphate (hydrolysis of ATP). Example, Na+/K+ antiport pump
- ABC transporters: Two binding regions for ATP. Example, eukaryotic MDRs
32
How does the Na+/K+ pump create and maintain a concentration gradient?
- Active transport to prevent gradient dissipating
- P-class transporters hydrolyses ATP
- Alpha unit of transporter binds to ions, transporter then changes shape allowing Na+ to leave cell/K+ to enter
- 3 Na+ leaves cell but only 2 K+ enters, maintaining electrochemical gradient
33
How was DNA discovered as the cellular genetic material?
- S-cell solution treated with protease, ribonuclease and deoxyribonuclease
- Transformation of R-cells into S-cells only occurs when DNA is present
- Radioactively labelled viruses used, 35-S in methionine (protein coat) and 32-P in DNA
- Infected E. coli cells only contained 32-P so only DNA is transferred
34
Describe the structure of nucleotides
- PENTOSE SUGAR - Ribose or 2' deoxyribose (oxygen lost from carbon-2 on main ring)
- NITROGENOUS BASE - Thymine/Cytosine/Uracil (pyrimidine, one ring) or Adenine/Guanine (purine, two rings). Purine pairs with pyrimidine in complementary base pairing
- PHOSPHATE GROUP - Up to three can be added to nucleoside
35
How are nucleotides joined together?
- Phosphodiester bonds between phosphate group of carbon-5 and hydroxyl group on carbon-3
36
What are the 10 structural features of B-DNA?
1) Double helix
2) Strands run anti-parallel
3) Complementary base pairing
4) Hydrophobic bases face inwards
5) Hydrophilic sugar-phosphate backbone faces outwards
6) 10 base pairs per turn
7) Length of turn is 3.4nm
8) Width of helix is 2nm
9) Each turn has a major and minor groove
10) The helical structure is right-handed
37
Which anti-cancer drugs target DNA and how do they work?
- Cisplatin - Covalently binds to guanine to prevent unwinding of DNA, and therefore replication
- Doxorubicin - Becomes intercalated into molecule by sliding in between bases
38
What is semi-conservative replication and how was it discovered?
- One strand of DNA newly formed and one from parent helix
- Bacteria originally grown on 15-N media (nitrogenous bases have 15-N), then transferred to 14-N media
- DNA separated by density - 1st generation contained 15-N and 14-N
39
What is the role of a replication fork in DNA replication?
- Replication fork formed when DNA is unwound the origin of replication - start of process
- When two replication forks meet replication is finished
40
What is the function of topoisomerase enzymes?
- Regulation of underwinding/overwinding of DNA
- Tension from overwinding created after a section is unwound - enzymes releases this tension to prevent it stopping replication
- Type 1: One strand cut then reannealed
- Type 2: Both strands cut, another helix is passed through and then strands are reannealed
41
What is the function of DNA polymerase III?
- Synthesis of new DNA molecules via replisome
42
What is the function of DNA helicase?
- H-bonds between base pairs broken using energy
| - Allows strand to unwind
43
What direction can DNA polymerase III work in?
- 5' to 3'
- Leading strand synthesised continuously
- Lagging strand synthesised in Okazaki fragments which are joined by DNA ligase
44
How does DNA replication begin?
- Primase enzyme makes RNA primer with a free 3' OH group
- Primer attaches to DNA to allow polymerase enzyme to attach and synthesise
- Primer then removed by DNA polymerase I
- Primer replaced by correct nucleotide by DNA polymerase III
45
Which enzymes to fluoroquinolones affect and what is their method of action?
- DNA gyrase (bacterial topoisomerase enzyme) - relaxes helix after unwinding
- Topoisomerase IV - Cuts strands to unlink replicated circular chromosomes in bacteria
46
What does Topotecan do?
- Becomes intercalated into DNA and inhibits topoisomerase I
| - Used in late stage cervical cancer and relapsed small cell lung cancer
47
What does Etoposide do?
- Inhibits topoisomerase II
| - Used for treatment of testicular cancer/lymphoma
48
What can DNA polymerase enzymes be used for in a lab setting?
- PCR
| - DNA sequencing
49
What is meant by the central dogma?
- DNA -> RNA -> Protein, by transcription and translation
50
What is Rifampicin used for and how does it work?
- Treatment of TB
| - Inhibits bacterial RNA polymerase
51
How are retroviruses treated? Give two examples with the treatments options
- HIV, treated with abacavir
- HSV, treated with acyclovir
- Drugs inhibit action of reverse transcriptase enzyme, preventing RNA being converted to DNA
52
What are introns and where are they found?
- Non-coding regions of DNA
| - Found in pre mRNA
53
What are exons and what is their function?
- Coding regions of DNA
| - Can be combined in various ways to create a protein transcript
54
How can one gene produce more than one type of protein?
- Introns removed from pre mRNA by spliceosomes
| - Exons can be combined in a number of different ways, creating a number of different mature mRNA strands
55
What are the main features of mRNA?
- At least one transcript per gene
- About 1200 nucleotides in mature mRNA
- Carry message from nucleus to ribosomes
- About 5% of all cells RNA
56
What are the main features of tRNA?
- About 75 nucleotides in one molecule
- ADAPTOR MOLECULE: transfer amino acids to peptide chain (therefore mRNA to protein)
- Amino acid attached to 3' end of tRNA
- About 15% of cellular RNA
57
What are the main features of rRNA?
- 1700-3700 nucleotides in one molecule
- "Scaffolding" for ribosomal proteins
- About 80% of cellular RNA
58
What are the three main phases of transcription?
- Initiation
- Elongation
- Transcription
59
What controls eukaryotic initiation?
- Transcription factors control binding of RNA polymerase
