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Semester 2 Missed Lectures > ICPP > Flashcards

ICPP Flashcards

1
Q

What does amphipathic mean for lipid membranes?

A

One part of the lipid membrane is hydrophilic and one part is hydrophobic:
- The phospholipid head interacts with water.
- The fatty acid tails avoid water.

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2
Q

What drives the structure of the lipid membrane?

A

Energetic stability - it is the conformation that requires the least energy to maintain.

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3
Q

Which conformation of phospholipids have a kink in the fatty acid tail?

A

Unsaturated, cis conformations.

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4
Q

What are the main parts of a phospholipid and what are the different types of the hydrophilic part?

A

There is a phosphate and polar head group, a glycerol backbone and 2 fatty acid chains. The polar head group can be:
- Amines.
- Amino acids.
- Choline.
- Inositol.

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5
Q

What is the difference between sphinogmyelin and a normal phospholipid?

A

It has no glycerol backbone, and instead contains a sphingosine molecule instead.
There are no ‘kinks’ as they are all trans isomers.
The fatty acid tails are often unequal lengths.

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6
Q

What is the structure of a cerebroside? Where are they usually found?

A

Contains a sphingosine group, a fatty acid tail and a monosaccharide (usually glucose or galactose) polar head group.

They are usually found in the myelin sheath of axons in the CNS and PNS.

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7
Q

What is the structure of a ganglioside and where are they found?

A

A sphingosine, a fatty acid tail and an oligosaccharide chain.

They are found extending out from cell surfaces, and important to the CNS.

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8
Q

What are the roles of cerebrosides?

A

Stabilising membranes.
Cell-to-cell recognition.
Immune system.

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9
Q

What are the roles of gangliosides?

A

Immune system.
Cell-to-cell signalling and CNS development.
Lipid rafts.

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10
Q

What are the structural characteristics of cholesterol?

A

Hydrophilic -OH head group.
Hydrophobic planar steroid ring with a small fatty acid tail.

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11
Q

What are the functions of cholesterol in membranes?

A

Compose about 30-40% of membrane lipids.
They enhance temperature range for membrane fluidity AND stability.
Lipid raft formation.

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12
Q

What is the trade off between fluidity and stability?

A

Too stable will restrict movement of proteins and inhibits permeability.
Too fluid will lose the organisation.

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13
Q

What are the main factors affecting membrane fluidity?

A

Temperature - the greater temperature, the greater the fluidity.
Molecular mass - the greater the molecular mass, the less able to move it is.

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14
Q

How does the fluid behaviour change between saturated and unsaturated lipids and why does this occur?

A

In the body, at 37 degrees Celsius, saturated phospholipids are solid as the melting point is between 45 and 75 degrees, compared to -6 of unsaturated, making them fluid-like.

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15
Q

What causes the increased fluidity of unsaturated phospholipid molecules?

A

The C to C double bond’s cis conformation creates a kink which makes the phospholipids harder to pack in together, increasing the space between phospholipids, disrupting the lattice structure.

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16
Q

How does cholesterol exerts its effects on the lipid membrane?

A

The hydroxyl polar head group interacts with polar head groups of other phospholipids, inhibiting movement.
The rigid steroid plates inhibit movement of fatty acid tails, increasing stability.
The angle of the steroid plates interferes with the crystalline packing, increasing fluidity.

PREVENTS ABRUPT CHANGES TO MEMBRANE FLUIDITY ACROSS TEMPERATURE RANGES.

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17
Q

What is a lipid raft, and what is its function?

A

It is a specialised distribution of lipids around 100nm long, with more cholesterol, sphingomyelin and glycolipids.

It is more structured to provide a stable environment for signalling proteins and for the holding of receptors and signalling molecules.

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18
Q

What is the relevance of the fluid mosaic model for the whole body function?

A

Fluidity and flexibility is required for protein function.
Cell membranes are required for the transmission of forces throughout cells and tissues.

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19
Q

What are the 2 types of peripheral proteins?

A

External membrane face (outside the cell).
Internal membrane face (inside the cell).

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20
Q

What is the role of the cytoskeleton and peripheral protein interactions?

A

Provides flexibility and elasticity to the cell membrane.
Disperses forces across the cell, preventing mechanical disruption.

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21
Q

What are lipid anchored proteins?

A

The are proteins included in the integral protein category due to the covalent bond formation between the protein outside the cell and the fatty acids inside the cell.
They can move laterally.

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22
Q

What are different protein interactions that can occur and their functions?

A

Aggregation - signalling.
Tethering externally - connect to the ECM for transmission of forces.
Tethering internally - connect to cytoskeleton for strength and flexibility.
Cell-to-cell interactions - cadherins that form tissues, transmit forces, and have a signalling role.

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23
Q

What is the function of Band 3 on RBCs?

A

HCO3-/ Cl- antiporter to transport CO2.

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24
Q

What does glycophorin do in RBCs?

A

Reduces friction forces.

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25
Q

What does ankyrin do in RBCs?

A

Anchors Band 3 to spectrin.

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26
Q

What keeps the cytoskeleton proteins of RBCs in place?

A

The polar/ ionic bonds.

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27
Q

How does cytochalasin disrupt the cytoskeleton formation?

A

Inhibits actin polymerisation, preventing the anchoring of spectrin and glycophorin occurring.

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28
Q

What type of molecules can pass straight through a lipid membrane? Give an example.

A

Hydrophobic molecules, like benzene.
Small uncharged polar molecules, like water.

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29
Q

What does Fick’s law state?

A

The rate of passive diffusion through a membrane depends on the permeability of the membrane and concentration gradient of the molecule.

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30
Q

What are the two mechanisms of bulk water flow and what are the characteristics of them?

A

Passive diffusion:
- Occurs across the entire surface of the cell membrane.
- It is bi-directional.
- Water crosses until the solute equilibrium is reached.

Facilitated diffusion - aquaporins:
- Integral membrane proteins.
- It is bi-directional.
- Equilibrium is reached rapidly.

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31
Q

What makes non-gated pores good at facilitating the ability to reach equilibrium quickly?

A

They are always open.

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32
Q

How do gated pores facilitate diffusion?

A

The molecule enters the pore, causing a conformational change, allowing the molecules to be released - it is ping-pong transport.

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33
Q

Outline the sequence of how carriers allow the movement of molecules into cells.

A

The carrier is open to molecules outside the cell.
The molecule enters the carrier, closing the cell to the outside.
The carrier undergoes a further conformational change, opening the carrier to the inside of the cell.
The molecule can then flow into the cell, and the carrier then closes off to the inside of the cell.

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34
Q

What are some characteristics of carrier proteins?

A

They allow facilitated diffusion to occur.
It involves binding and conformational changes to occur.
A limited number of substances can be moved.
The central pore is usually aqueous.

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35
Q

What are the two types of carrier proteins?

A

Uniporters - they transport one molecule at a time down the concentration gradient.

Co-transporters - these can be symporters that allow two or more substances to flow in the same direction, or antiporters that transport two or more substances in opposite directions.

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36
Q

What are some physiological roles of transport processes?

A

Maintain ionic compositions.
Maintain pH.
Maintain cell volume.
Expulsion of waste products.
Generation of ionic gradients for electrical excitability.
Metabolic fuel transport.

37
Q

What are the functions of the sodium-potassium ATPase?

A

Forms sodium and potassium gradients, necessary for electrical excitability.
Drives secondary active transport for:
- pH control.
- Cell volume regulation.
- Absorption of sodium into epithelial cells.
- Nutrient uptake (glucose or amino acids).

38
Q

What is the difference between the PMCA and NCX?

A

PMCA uses primary active transport. It has high affinity but low capacity for calcium. It is a uniporter.

NCX uses secondary active transport with a low affinity but high capacity for calcium. It is an antiporter.

39
Q

What is the exchange that occurs in the sodium-calcium exchanger (NCX)?

A

It removes 1 Calcium ion for every 3 sodium ions, making it electrogenic - one more positive charge is brought into the cell than is removed.

40
Q

What is the glucose transport mechanism in the gut?

A

Microvilli on the enterocytes express SGLT1 transporters. These co-transport sodium and glucose into the cell.
The GLUT2 molecules than transport most of the glucose into the interstitial space.

Some of the glucose also leaves via passive diffusion and the rest is utilised by the enterocyte.

41
Q

How is sucrose absorbed through the gut?

A

The sucrose-H+ ion symporter uses secondary active transport from the K+/H+ ATPase to pull sucrose into the enterocyte.
The sucrose is catabolised to glucose and fructose and then the glucose uses the GLUT2 transporter to transport the glucose into the blood.

42
Q

Explain the different SGLT and GLUT transporters that are used to re-absorb kidney in the proximal convoluted tubule.

A

In the first 1/3rd. SGLT2 is used to draw about 90% glucose into the enterocyte, using 1 sodium ion - it has a high capacity but low affinity. The GLUT2 transporter then transports the glucose into the blood.

In the rest of the PCT, SGLT1 is used, which uses 2 sodium ions which has a much higher affinity but lower capacity. The remaining 10% it drawn into the enterocyte and GLUT1 then transports it into the blood.

43
Q

What is the main action of SGLT1 and SGLT2 inhibitors when treating diabetes mellitus?

A

SGLT2 inhibitors inhibit the reabsorption of glucose in the kidney.

SGLT1 inhibitors inhibit the absorption of glucose in the intestine.

44
Q

What are the 2 pathways of glucose transport in the CNS?

A

1) glucose is converted to lactate by the astrocyte and transported to the neurone.
2) glucose is transported by GLUT1 from the endothelial cells into the interstitial space and then transported into the neurone by GLUT3.

45
Q

What is the membrane potential of:
- Cardiac myocytes
- Neurones
- Skeletal muscle cells
- Smooth muscle cells

A

Cardiac myocytes = -85mV.
Neurones = -70mV.
Skeletal muscle = -90mV.
Smooth muscle = -50mV.

46
Q

How are cell membranes permeable to ions and what are the properties of them?

A

They contain ion channels that are:
- Selective to one or few ions.
- They are gated; can be opened or closed by conformational changes.
- Have a rapid movement of ions down the electrochemical gradient.

47
Q

What is the electrochemical gradient?

A

The electrical gradient is the charge difference that pulls the ions in one direction or another.
The chemical gradient is the concentration gradient of that chemical.

48
Q

What is the equilibrium potential of an ion?

A

The balance between the electrical and chemical gradient - the ion continues to move until the gradients are in equilibrium.

49
Q

What ion equilibrium potential is the resting membrane potential based off of the most and why is this the case?

A

The potassium ion as the membrane is most permeable to this ion, due to there being the greatest proportion of leaky potassium ion channels in the membrane.

50
Q

What are the equilibrium potentials for calcium, sodium, chloride and potassium ions?

A

Calcium = +120mV
Sodium = +60mV
Chloride = -70mV
Potassium = -95mV.

51
Q

What is the role of the sodium/ potassium ATPase in resting membrane potentials?

A

It is to maintain the potential by maintaining the electrochemical gradients of the ions.

52
Q

What 3 factors determines the resting membrane potentials of cells?

A

The concentrations of ions intracellularly and extracellularly.
The permeability of cell membrane to each ion via specific ion channels.
Electrogenic pump activities.

53
Q

What does depolarising mean?

A

The inside of the cell membrane becomes more positive.

54
Q

What does hyperpolarising mean?

A

The inside of the cell membrane becomes more negative.

55
Q

What do excitatory vs inhibitory transmitters do?

A

When bound to, excitatory open ligand-gated ion channels that depolarise the cell membrane, whereas inhibitory open ligand-gated ion channels that hyperpolarise the cell membrane.

56
Q

What does repolarisation mean?

A

The inside of the cell membrane becomes more positive, from a hyperpolarised state back to the resting membrane potential.

57
Q

Where in the neuron is the action potential initiated?

A

The axon hillock.

58
Q

What is the state of the sodium channels in the absolute refractory period and relative refractory period, and what does this mean?

A

ARP = they are inactivated, meaning they cannot be opened.

RRP = they are closed, meaning they can open again if they are depolarised.

59
Q

How does inactivation particle prevent sodium influx?

A

The loop enters the pore, preventing sodium ions form being able to enter.

60
Q

What is the difference in structure between a voltage-gated sodium channel and a voltage-gated potassium channel?

A

Sodium = consists of 4 repeat units forming 1 alpha subunit.

Potassium = consists of 4 individual alpha subunits that come together.

61
Q

What is the relevance of the 4th transmembrane domain of voltage-gated sodium and potassium channels?

A

They are positively charged and can sense a change in voltage, stimulating a conformational change to occur.

62
Q

In what state of the voltage-gated sodium channel does lidocaine work best in, and in what state does lidocaine block the channel?

A

When the channel is inactivated.
Lidocaine blocks the channel when it is protonated.

63
Q

What is the length constant of an action potential? What is the relevance of this for velocity?

A

The distance it takes for the potential to fall to 37% of the original value.
This means that the greater the length constant (the greater the distance), the greater the velocity.

64
Q

Where are the voltage gated sodium and potassium channels located along the myelinated axon?

A

Sodium = nodes of Ranvier.

Potassium = juxtaparanode.

65
Q

What is the optimum ratio of diameter of axon to diameter of neuron?

A

d/D = 0.7 gives the greatest conduction velocity.

66
Q

What is the effect of increasing action potential frequency at the nerve terminal?

A

Increasing the concentration of calcium influx, increasing the amount of neurotransmitter released.

67
Q

Describe the process of neurotransmitter release at a neuromuscular junction?

A
68
Q

Where are ryanoide receptors located and what do they do?

A

They are located on the sarcoplasmic reticulum membrane and efflux calcium ions into the cytoplasm for a greater force of muscular contraction.

69
Q

Activation of which receptors, with what agonist can cause bronchoconstriction?

A

M3 receptors with acetylcholine.

70
Q

What are orphan receptors?

A

Receptors that do not have identified ligands.

71
Q

What is a ligand?

A

A molecule that can bind specifically to a receptor.

72
Q

What is association and dissociation?

A

Association is the ability for a ligand to bind to a target, and dissociation is the ability of a ligand to come off of a target.

73
Q

How can we measure binding, experimentally?

A

Fluorescently label the ligand.
Introduce a known concentration of ligand to a known concentration of receptor.
Determine how much of the ligand is bound to the receptor.

74
Q

What 3 things does potency depend on?

A

The affinity and intrinsic efficacy of the drug for the receptor, and tissue-dependent factors.

75
Q

What is selective efficacy?

A

Where a drug has a greater intrinsic efficacy for one site of action over another.

76
Q

What is selective affinity?

A

Where a drug has a higher affinity for one site of action over another.

77
Q

Explain how the treatment of asthma is functional antagonism.

A

The binding of a ligand to the beta-2 adrenoceptors causes relaxation of the bronchial smooth muscle, causing bronchodilation. This means that more air can flow into the lungs and oxygenate the blood.

78
Q

What are some tissue-dependent factors?

A

How much a muscle can contract.
How much a gland can secrete.

79
Q

Explain the term functional antagonism.

A

There is antagonism of a cell or tissue, due to the binding of a ligand to its site of action.

Note: it is the cell or tissue, not the receptor, that is being antagonised.

80
Q

What is IC50?

A

The concentration of antagonist required to inhibit 50% of the maximal response.

81
Q

What is the orthosteric site?

A

The site at which the endogenous ligand binds.

82
Q

What are the similarities and difference between facilitated diffusion and secondary active transport in drug absorption?

A

Similarities:
- They both use OATs and OCTs.

Differences:
- Facilitated diffusion allows the drug to move down the concentration gradient.
- Secondary active transport uses another ions electrochemical gradient to move the drug against its concentration gradient.

83
Q

Where does first pass metabolism occur and what kind of enzymes are involved?

A

It occurs in the gut lumen, where at here are some gut/ bacterial enzymes.
It occurs in the gut wall, and in the liver, where there are phase I and phase II enzymes.

84
Q

What are phase I and phase II enzymes?

A

Phase I = cytochrome P450 enzymes.
Phase II = conjugating (cytosolic) enzymes.

85
Q

Define bioavailability.

A

The fraction of a defined dose which reaches its way into a specific bodily compartment.

86
Q

What is bulk flow and diffusion of a drug?

A

Bulk flow is the large distance that the drug moves via arteries to capillaries.

Diffusion is the small distance that the drug moves across the capillaries into the interstitial fluid and cell targets.

87
Q

What are the barriers to diffusion?

A

Interactions - more common in charged molecules.
Local permeability - the type of capillary.
Non-target binding - often seen with protein binding.

88
Q

How do drugs bind to albumin and what is the affect?

A

It binds non-covalently, meaning that it can be displaced.
It binds to multiple binding site.
It decreases the therapeutic effect.

89
Q

What can affect the apparent volume of distribution?

A

Hypoalbuminaemia - increases free drug concentration.
Changes of blood flow to certain areas.
Other drugs.
Renal, liver or heart failure.
Pregnancy.
Paediatrics.
Geriatrics.

Semester 2 Missed Lectures (5 decks)

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