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Pharmacy - Year 1 > The Patient - Sem1 > Flashcards

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
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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
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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
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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

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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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16
Q

What are integral proteins?

A
  • Embedded in the membrane, usually span the entire membrane

- Usually alpha-helical structures

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17
Q

What are peripheral proteins?

A
  • Loosely associated with membranes

- Cytosolic or extracellular

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18
Q

How are membranes synthesised?

A
  • Growth of existing membranes
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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
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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
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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
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22
Q

What are multi drug transporters?

A
  • Pump a number of drugs out of cells, reducing their efficacy
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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
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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
Q

What is simple diffusion?

A
  • The movement of small molecules down a concentration gradient through a partially permeable membrane
  • Gasses and small polar molecules can pass through membrane
26
Q

What is facilitated diffusion?

A
  • The movement of small molecules down a concentration gradient through proteins embedded in the membrane
  • Faster than simple diffusion
27
Q

What is active transport?

A
  • The movement of small molecules across a membrane using energy from ATP, movement is against the concentration gradient
28
Q

What are the types of simultaneous transport of molecules?

A
  • Symport carrier proteins - Simultaneous transport of molecules in the same direction
  • Antiport carrier proteins - Simultaneous transport of molecules in opposite directions
29
Q

What are the types of proteins used in facilitated diffusion?

A
  • Channel proteins - Water filled pores that allow ion transport
  • Carrier proteins - Changes shape when solute binds (much slower than channel)
30
Q

What is saturation in terms of facilitated diffusion?

A
  • Saturation occurs when all transporters are being used
31
Q

What are the two types of transport proteins used in active transport and what are their structures? Give an example of each

A
  • 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
Q

How does the Na+/K+ pump create and maintain a concentration gradient?

A
  • 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
Q

How was DNA discovered as the cellular genetic material?

A
  • 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
Q

Describe the structure of nucleotides

A
  • 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
Q

How are nucleotides joined together?

A
  • Phosphodiester bonds between phosphate group of carbon-5 and hydroxyl group on carbon-3
36
Q

What are the 10 structural features of B-DNA?

A

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
Q

Which anti-cancer drugs target DNA and how do they work?

A
  • Cisplatin - Covalently binds to guanine to prevent unwinding of DNA, and therefore replication
  • Doxorubicin - Becomes intercalated into molecule by sliding in between bases
38
Q

What is semi-conservative replication and how was it discovered?

A
  • 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
Q

What is the role of a replication fork in DNA replication?

A
  • Replication fork formed when DNA is unwound the origin of replication - start of process
  • When two replication forks meet replication is finished
40
Q

What is the function of topoisomerase enzymes?

A
  • 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
Q

What is the function of DNA polymerase III?

A
  • Synthesis of new DNA molecules via replisome
42
Q

What is the function of DNA helicase?

A
  • H-bonds between base pairs broken using energy

- Allows strand to unwind

43
Q

What direction can DNA polymerase III work in?

A
  • 5’ to 3’
  • Leading strand synthesised continuously
  • Lagging strand synthesised in Okazaki fragments which are joined by DNA ligase
44
Q

How does DNA replication begin?

A
  • 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
Q

Which enzymes to fluoroquinolones affect and what is their method of action?

A
  • DNA gyrase (bacterial topoisomerase enzyme) - relaxes helix after unwinding
  • Topoisomerase IV - Cuts strands to unlink replicated circular chromosomes in bacteria
46
Q

What does Topotecan do?

A
  • Becomes intercalated into DNA and inhibits topoisomerase I

- Used in late stage cervical cancer and relapsed small cell lung cancer

47
Q

What does Etoposide do?

A
  • Inhibits topoisomerase II

- Used for treatment of testicular cancer/lymphoma

48
Q

What can DNA polymerase enzymes be used for in a lab setting?

A
  • PCR

- DNA sequencing

49
Q

What is meant by the central dogma?

A
  • DNA -> RNA -> Protein, by transcription and translation
50
Q

What is Rifampicin used for and how does it work?

A
  • Treatment of TB

- Inhibits bacterial RNA polymerase

51
Q

How are retroviruses treated? Give two examples with the treatments options

A
  • HIV, treated with abacavir
  • HSV, treated with acyclovir
  • Drugs inhibit action of reverse transcriptase enzyme, preventing RNA being converted to DNA
52
Q

What are introns and where are they found?

A
  • Non-coding regions of DNA

- Found in pre mRNA

53
Q

What are exons and what is their function?

A
  • Coding regions of DNA

- Can be combined in various ways to create a protein transcript

54
Q

How can one gene produce more than one type of protein?

A
  • 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
Q

What are the main features of mRNA?

A
  • 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
Q

What are the main features of tRNA?

A
  • 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
Q

What are the main features of rRNA?

A
  • 1700-3700 nucleotides in one molecule
  • “Scaffolding” for ribosomal proteins
  • About 80% of cellular RNA
58
Q

What are the three main phases of transcription?

A
  • Initiation
  • Elongation
  • Transcription
59
Q

What controls eukaryotic initiation?

A
  • Transcription factors control binding of RNA polymerase

Pharmacy - Year 1 (2 decks)

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