Pharmacology

Question 1

functions of membrane proteins

Answer 1

intercellular joining, enzymatic activity, transport, cell-cell recog, anchorage, signal transduction

Question 2

4 types of receptors

Answer 2

1. Some receptors form a channel across the membrane (1)
2. Some receptors transmit a signal across the membrane via G protein and 2nd messenger (2)
3. Some receptors are membrane bound enzymes (3)
4. Some receptors are intracellular so won’t be covered in this block (4)

Question 3

features of a receptor

Answer 3

• Several binding sites
• Bind ligands
• Releases ligand unchanged
• Can be membrane bound or free in cytosol

Question 4

features of enzymes

Answer 4

• Generally one active site
• Bind substrates
• Changes substrate into product
• Can be membrane-bound or free in cytosol

Question 5

what is a receptor

Answer 5

protein molecule that receives chemical signal from outside cell

Question 6

what is a ligand

Answer 6

molecule or drug that binds to receptor.

2 types:

• agonist and antagonist

Question 7

agonist

Answer 7

chemical capable of activating a receptor to induce a response - this is not always a positive response (increases action of a receptor)

Question 8

antagonist

Answer 8

a drug that counteracts the effects of another drug or molecule (blocks action of a receptor)

Question 9

method of action of aspirin

Answer 9

1. Aspirin (ASA) binds the active site of the COX-2 enzyme
2. This prevents Arachidonic Acid (AA) from binding
3. No Prostaglandin (PG) is produced
4. No inflammation
5. Reduced pain

Question 10

two types of COX enzyme

Answer 10

• COX-2 - Converts arachidonic acid to prostaglandin causing inflammation and pain
• COX-1 - Expressed in all cells, helps regulate the release of stomach acid. Therefore inhibition of this enzyme causes increase in stomach acid which results in stomach ulcers. At the same time, pain and inflammation in stomach decreases

Question 11

increasing selectivity of anti-inflammatory drugs

Answer 11

“coxib” drugs like celecoxib specific to COX-2 have reduced side effects but still have anti-inflammatory effects

Question 12

key groups of receptors

Answer 12

Ion channel, G-protein coupled receptor, enzymes

Question 13

receptor for alcohol

Answer 13

GABA_A​

• ionotropic, membrane bound, ligand gated chloride channel

Question 14

alcohol and GABA

Answer 14

• GABA is inhibitory - slurred speech, memory loss and reduced inhibition
• alcohol is an agonist
• Receptor is ionotropic (ion channel)
• Ethanol binds to GABAA ionotropic receptor, blocking GABA from binding
• Agonist binding opens the channel and allows chloride ions (Cl-) into the cell
• Alcohol changes AA sequence which affects secondary structure so subunit makeup of GABA receptor is changed

Question 15

receptor for cannabis

Answer 15

cannabinoid receptor

• G-Protein Coupled
• both inhibitory and stimulatory effects simultaneously
• High concentrations of CB1 in the brain
• CB2 is found around the body e.g. spleen and pancreas

Question 16

receptor for aspirin and ibuprofen

Answer 16

COX-1 and COX-2

Question 17

marijuana and cannabinoid receptor

Answer 17

• use a complex of proteins called G-proteins to send a signal from the membrane bound receptor to intracellular targets
• Targets can be internal enzymes such as adenylate cyclase (forming cAMP) or can be other receptors such as an ion channels
• Activation of CB1 causes appetite stimulation, euphoria, relaxation, anxiety and hallucinations
• Cannabis is considered to be a very good analgesic (pain killer) but it has a range of side effects including hallucinations

Question 18

why is it called fluid mosaic model

Answer 18

Membrane is made up of many different components (Glycolipids, glycoproteins, phospholipids, cholesterol, integral proteins) which gives it a mosaic appearance, which can all move around each other in a fluid manner

Question 19

structure of phospholipid

Answer 19

Two hydrophobic fatty acids and a hydrophilic phosphate connect with glycerol to form phosphatidic acid

Question 20

fatty acid chain of phospholipid

Answer 20

can be saturated (no double bonds) or unsaturated (double bonds). even number of C’s and connected by ester bond

Question 21

movement of phospholipids

Answer 21

• Move left to right and back and forth - this happens rapidly
• Can switch sides of bilayer however this is slow and rare bc polar head has to move through hydrophobic tail region - ‘flip-flopping’

Question 22

what affects membrane fluidity

Answer 22

1. temperature
2. type of fatty acid
3. presence of cholesterol

Question 23

effect of temperature of membrane fluidity

Answer 23

At higher temperatures, the phospholipids have more energy, and thus move around more AND the energy input breaks the Van der Waals interactions → phospholipids cannot pack close together → membrane fluidity increases

Question 24

effect of type of fatty acid on fluidity

Answer 24

• Unsaturated fatty acids increase the fluidity of a membrane by preventing the phospholipids from packing close together because a double bond in a hydrocarbon tail kinks the fatty acid chain
• Shorter fatty acid chains have fewer Van der Waals interactions between them, hence an overall weaker interaction between adjacent hydrocarbon tails compared to long ones, increasing the fluidity of the membrane

Question 25

effect of cholesterol on fluidity at low temperature

Answer 25

cholesterol is a bidirectional regulator - it prevents too close packaging of phospholipids when its hydrophobic rings interacts with/binds to adjacent hydrocarbon tails, partly immobilising those phospholipids → membrane fluidity is maintained at low temperatures and freezing (crystallization) is prevented

Question 26

effect of cholesterol on fluidity at high temperature

Answer 26

bidirectional regulator - many cholesterol molecules inserts themselves in the membrane (as there is more space between the phospholipids). The hydrophobic rings of the cholesterol interacts with/binds to adjacent hydrocarbon tails, partly immobilising those phospholipids → decrease membrane fluidity

Question 27

sphingolipids

Answer 27

* type of membrane lipid * based on sphingosines (amino alcohols) instead of glycerol * abundant in myelin sheaths around nerve cells

Question 28

glycolipids

Answer 28

side chains attached by glycosidic (sugar-like) linkage (common in plants)

Question 29

how are proteins attached to lipid bilayers

Answer 29

* Proteins can be attached to lipid bilayers by partially inserted proteins * Fatty acids can be used to anchor proteins in the membrane - post-translational addition of lipids

Question 30

channel proteins

Answer 30

* when open, a channel is open to both the intracellular and extracellular space * Forms a polar core through which polar molecules can move down their concentration gradient * can open and close spontaneously or be regulated (“gated”) * rate of transport can approach rate of diffusion: 107 -108 molecules per second * e.g. aquaporin

Question 31

transporter proteins

Answer 31

* transporters are open to either the intracellular or the extracellular space * binding induces a conformational change * rate of transport: 102 -103 molecules per second * transporters have several features in common with enzymes * Can only transport specific molecules * e.g. glucose transporter GLUT

Question 32

permeability coefficient

Answer 32

describes how easy and fast a molecule can move across a membrane

Question 33

transport of non-polar molecules e.g. O2 and CO2

Answer 33

* Small, non-polar molecules, e.g. oxygen and carbon dioxide, are so small that they can fit through the spaces in the membrane * More hydrophobic = more permeable = moves through membrane faster * Larger concentration gradient = increase rate of transport for a non-polar molecule across a lipid bilayer

Question 34

non mediated

Answer 34

does not require protein

Question 35

mediated

Answer 35

requires protein (facilitated)

Question 36

passive

Answer 36

down a conc gradient

Question 37

active

Answer 37

requires an input of energy to move a molecule up its concentration gradient. Energy may come from the hydrolysis of ATP (primary active transport) or the co-transport of another molecule down its concentration gradient (secondary active transport)

Question 38

symport cotransport

Answer 38

* both molecules move in the same direction. * Molecules should be moving in opposite gradient directions. * E.g. Na+ down a gradient which releases energy. * Glucose uses this energy to move up a gradient. * Both moving in the same direction

Question 39

antiport cotransport

Answer 39

* the two molecules move in opposite directions. * e.g. Na+ down a gradient. Ca+ up a gradient. * Moving in opposite gradient directions

Question 40

Na+/K+ ATPase

Answer 40

1. cytoplasmic Na+ binds to Na+/K+ pump 2. Na+ binding stimulates phosphorylation by ATP 3. phosphorylation causes conformational change in protein, expelling Na+ to outside 4. extracellular K+ binds to protein triggering release of phosphate group 5. loss of phosphate restores proteins original conformation 6. K+ is released and Na+ sites are receptive again