Proteins Flashcards

1
Q

What is the pH range for human blood?

A

7.35-7.45

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2
Q

What are the 3 mechanisms that maintain pH in humans?

A

The renal system
The respiratory system
Chemical buffering system

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3
Q

What are the 3 types of chemical buffers?

A

Bicarbonate, phosphate and protein

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4
Q

Describe the bicarbonate reaction:

A

The dissolution of carbon dioxide in water, catalysed by the enzyme carbonic anhydrase produces carbonic acid (a weak acid). This can then dissociate in an equilibrium to produce bicarbonate and hydrogen ions.

CO2 + H2O <> H2CO3 <> HCO3- + H+

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5
Q

Describe what the Bohr effect is:

A

The pH of blood in the lungs has a higher pH than that of the tissues which have a lower pH which promotes the release of oxygen at the tissues. Deoxyhaemoglobin has no o2 and is called the T state. The R state is the oxygemoglobin. If the T state is stabilised then the oxygen is released into the tissues

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6
Q

What are fibrous proteins?

A

Secondary structures with highly regular, repetitive amino acid sequences. They have both mechanical and structural strength

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7
Q

What are 3 examples of fibrous proteins?

A
  1. Keratin (wool)
  2. Fibroin (silk)
  3. Collagen (skin)
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8
Q

Describe the properties of a fibrous proteins (alpha helix)

A

They are helical proteins with cross linking S-S bonds. They are tough insoluble protective structures of varying hardness and flexibility. They are right handed and have 3.6 amino acids per turn. Every H does H bonding and the C=O of residue 1 H-bonds with the H-N of residue 5. They are rigid, coiled and compact.

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9
Q

Describe the properties of a fibrous proteins (B sheet)

A

They are sheet forming proteins that form soft and flexible filaments.

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10
Q

Describe the B sheet structure of fibroin (silk):

A

It is a repetitive sequence with alternating alanine and serine layers. There is variable spacing and interdigitation

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11
Q

Describe the alpha helix structure of keratin (wool/hair)

A

It contains a long alpha helix with a globular head where every 4th residue is hydrophobic. 2 molecules coil up so that the hydrophobic is in the middle and hydrophilic on the outside. Filaments are held together by hydrogen, ionic or disulfide bonds

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12
Q

Describe wet hair:

A

When the hair is wet, the water molecules break the H bonding so the alpha helices filaments can slide back and fourth and then when they are dry the hydrogen bonds form again so the hair is set in place.

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13
Q

What is the protein associated with curly hair?

A

Cystine - it forms disulfide bonds which disrupt the shape

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14
Q

Describe non polar side chains:

A

They have lots of carbons and are found on the inside of protein molecules

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15
Q

Describe polar side chains:

A

They have electronegative atoms like OH, S, NH2 etc. Acidic charged side chains are -ve i.e they have lost a proton and basic side chains are +ve because they have gained a proton

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16
Q

What is the definition of toughness?

A

The ability to absorb energy without breaking

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17
Q

Describe the structure of spindroin (spider silk):

A

Sticky, stretchy and tougher than steel and tevlon because of the mixture of beta sheet nano-crystalline regions and amphorus regions

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18
Q

What makes up a salt bridge?

A

A positive and negative charge i.e a electrostatic interaction

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19
Q

What happens when protein folding goes wrong, what diseases can you get?

A

Amyloid diseases:

  • alzeimers
  • huntingtons
  • prion disease
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20
Q

What are prions?

A

They are infectious proteins which cannot replicate themselves. They are misshapen versions of normal brain proteins which interact with normal proteins which then also becomes mis folded and exposes pieces of polypeptide chains. These molecules then aggregate into large beta sheets and accumulate deposits in the body.

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21
Q

How are proteins folded in such a short time?

A

It is very cooperative and they fold up by progressive stabilisation of intermediates structures rather than by random search. The randomly selected but correct intermediates are retained because they are slightly more stable than unfolded ones.

22
Q

What are the 2 types of unstructured proteins?

A
  1. Intrinsically unstructured proteins - don’t have a defined structure until they react with other molecules in the body
  2. Metamorphic proteins exist in an ensemble of structures of approx equal energies that are in equilibrium.
23
Q

How does fibril formation drive disease?

A

When normal proteins fold, they attain low energies, when fibrils form they can be very low energy forms which drives disease as they are so stable

24
Q

What is the order of intermediates from mis folded proteins to amyloid diseases with fibril formation?

A

There is little energy difference between the native protein, unfolded protein and mis folded protein. Once the protein is mis folded it can turn into an oligomer which can then go to either a protofibril (and then a fibril) or an amphorus aggregation - which are the 2 intermolecular contacts

25
Q

Describe the protein stability of most proteins:

A

They are only just stable so there is very little energy difference between folded and unfolded states of globular proteins

26
Q

What are 2 examples of very stable proteins?

A

GFP

Antibodies

27
Q

Describe globular proteins:

A

Spherical and water soluble proteins. They fold up and are held together by many weak interaction. They are easy to unfold or denature. Marginal stability is favoured by evolution.

28
Q

What is the driving force for protein folding?

A

The hydrophobic effect

29
Q

What is the hydrophobic effect?

A

Non-polar side chains cannot interact favourably with water so they cluster together in the interior of the protein molecule where they are away from the water

30
Q

What sort of interactions does the following disrupt: reducing agents?

A

Disulfide bonds

31
Q

What sort of interactions does the following disrupt: pH

A

Affects charge interactions

32
Q

What sort of interactions does the following disrupt: heat

A

All of them

33
Q

What sort of interactions does the following disrupt: organic solvents?

A

Hydrophobic

34
Q

What sort of interactions does the following disrupt: detergents

A

Hydrophobic

35
Q

What do antibodies need to bind to antigens?

A

They must bind with high affinity and selectivity

36
Q

Define domains:

A

Separately folded parts of the same protein

37
Q

Why is there domains?

A

Efficient folding: Longer chains in domains of 100-300 amino acids. Active sites created in clefts between domains. Different activities combined, allows flexibility which allows for domains to close over a bound substance

38
Q

What is quaternary/oligomeric structure?

A

Several seperate polypeptide chains clustered together

39
Q

Describe the structure of an antibody:

A

They are multi-domain and multi-chain proteins that are Y shaped. There are 2 heavy chains folded into 4 domains each and 2 light chains folded into 2 domains each. There are flexible hinges in between domains and binding site clefts. Each site (2 identical ones) has 6 hypervariable loops, meaning there are 12 in total

40
Q

Describe an antibodies binding affinity:

A

The antibody can bind 2 antigens at the same time with adjustable distance which gives the strongest binding. They can also bind to a single antigen but the affinity is half

41
Q

Describe the 4 factors of molecular recognition:

A

Shape
Size
Charge
Polar/non-polar

42
Q

On the outside of a flu particle, which bit are the neurominidase?

A

The circles

43
Q

On the outside of a flu particle, which bit are the hemagglutinin?

A

The little squares

44
Q

Where did influenza A originate from and when was the first pandemic?

A

Domestication of animals, first was in 1580 and there was 3 per century for the past 300 years

45
Q

Describe the influenza A in 1918:

A

Originated in china, mutated in Boston and spread to France by soldiers. Killed 50-100 million people. Due to a cytokine storm so young healthy people were affected and old and immune compromised were fine

46
Q

Describe the life cycle of a flu particle:

A

It comes into contact and adheres to the the human skin using hemogluttinin (little squares). These bind to saialic acid receptors which are proteins on the outside of the cell that has a carbohydrate segment and a saialic acid on top. It goes into the cell via endocytosis it undergoes fusion and uncoating which leads to the production of viral mRNA and protein synthesis and then it tries to get out of the cell to infect other cells but it will get stuck. The neurominidase cleaves away the sailalic acid from the carbohydrate so that it can be released

47
Q

Why can humans get pig flu but not bird flu?

A

Pigs have both alpha 2,3 SA receptors (bird) and alpha 2,6 receptors (humans) so they are like mixing vessels. Humans do have the alpha 2,3, but only in their lungs and they have alpha 2,6 in their airways so there is no way for the virus to get in.

48
Q

What does neurominidase do?

A

Removes the saialic acid from the newly formed virus particles as they try to emerge which stops them sticking together and allows new particles to escape

49
Q

What does haemagglutinin do?

A

Binds to sailic acid on host cells and gives entry to cells

50
Q

What is the aim of flu drugs?

A

To block the active site of neurominidase