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Bcem 431 > Lecutre 13 > Flashcards

Lecutre 13 Flashcards

(49 cards)

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1
Q

What is an example of a protein that has a gpi anchor

What disease does it contribute to

A

The prion protein on its c terminal domain

Mad cow disease

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2
Q

What causes mad cow disease

A

Being prion protien being resistant to Proteinase K

Can’t be chopped up and causes other protiens to misfold

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3
Q

What is does a normal prion protein look like (prpc)

A

Has a hydrophobic region

Binds cu2+ in square pyramidal geometry (binds nitrogen’s so intermediate)

Has glycosylated recptors

Has an octa repeat peptide

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4
Q

What is the sequence of the octa repeat residues in the prion protien

A

PH GGG WGQ

these repeats bind the copper ions

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5
Q

What is the disease version of the prion protein

A

Prpsc

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6
Q

What are the types of prion diseases

A

Creutzfeild Jakob disease : due to old age or exposure to infected cow/human brain)

BSE: when cows are exposed to infected cow brain (mad cow diease)

Kuru: humans ingest infected human brain

Fatal familial insomnia : rare Mutation in PRNP (prion protien) gene

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7
Q

What are prion protiens important for

A

Neuroprotection

Signalling in the brain due to gpi anchor

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8
Q

What is the role of the phospholipase enzyme (PI-PLC)

A

It can cleave the gpi anchor chain from the membrane

So I release the proton and the anchor in the extracellular space

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9
Q

Cysteine Thiol groups are

A

Redox sensitive (oxidative vs reducing environment)

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10
Q

What is HSA

A

Human serum albumin

Most important protein in the blood serum

Has 7-9 fatty acid binding sites

Heart shaped

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11
Q

Where is HSA mainly made, as what type of protein

A

In the liver

As a preproprotein

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12
Q

Molecular weight of HSA

A

66kDa

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13
Q

The half-life of HSA is

A

Long

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14
Q

HSA in the plasma is

A

Very densely packed

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15
Q

Is HSA a glycoprotien

A

No

Rare because extracellular proteins are usually glycosylated

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16
Q

How much of protein in the blood serum is HSA

A

60%

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17
Q

Is there more HSA outside the blood vessels or inside

A

More HSA outside the blood vessel

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18
Q

What is the function of HSA in the blood vessels

A

To maintain the osmotic pressure of plasma inside the cells

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19
Q

What can you say if HSA is not found in the urine

A

This means that HSA doesn’t usually leave the blood

We don’t lose HSA, very kept inside the blood

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20
Q

What does HSA bind

Study These Flashcards
A

fatty acids 7-9 in the plasma

steroid and thyroid hormones (like thyroxine)

Hemin

Metal ions like cu ni zn 2+ (intermediate metals)

21
Q

What is hemin

Study These Flashcards
A

Same as hemoglobin but instead of oxygen bound to fe , cl is bound

The chlorine turns fe2+ to 3+ (ferric)

22
Q

Structure of thyroxine

23
Q

How many binding sites does HSA have

Study These Flashcards
A

Multiple

Ex. Binds 1 hemin and 7 fatty acids at the same time

24
Q

HSA is mainly ______

How many domains is HSA

how many subdomains

What is it cross linked by

How many drug binding sites

Study These Flashcards
A

Alpha helical

3

2 in each of the 3 domains

Disulphide bonds

2

25
Why does HSA have disulphide bonds
Because it is outside the cell in oxidize environment
26
How many free cysteine in HSA
1 rest are disulphide bonds
27
Where do the disulphide linkages occur in HSA
Only in between the subdomain in each of the three domain None in between the three domains
28
Where can we make recombinant HSA and why
Only in yeast strains since ecoli can’t make disulphide bonds
29
Where can we make recombinant HSA and why
Only in yeast strains since ecoli can’t make disulphide bonds
30
What is the ATCUN site
This is the site in the HSA that binds copper and nickel at the amino terminal Binds cu2+ and ni2+ (square planar, intermediate)
31
What is the most importantly amino acid in the HSA ATCUN site
The histidine Since it’s imidazole ring binds the intermediate metals via nitrogen
32
What where does HSA deliver cu2+
Important do cu2+ going To the liver
33
What is the largest pool of copper? Second largest
Ceruloplasmin HSA
34
HSA also has a _____ binding site
Zinc2+ But doesn’t binds to the ATCUN site
35
What amino acids and in which domains make the zinc binding site in HSA
Between domains 1 and 2 two his side chains
36
What releases the zinc from the zinc binding site
If a fatty acid binds to HSA Then the two his that bind the zinc are too far apart and the zinc is released So zinc being there depends on fatty acid binding
37
How many fatty acids can bind to HSA What types does it bind to
7-9 sites for each fatty acid They are buried in the HSA because they’re hydrophobic Binds both saturated and unsaturated fatty acid
38
What drug binds to site 1 of HSA Site 2
Warfarin (blood thinner, prevent blood clot forming, block rectivation of vitamin K) Diazepam (also called Valium, anti anxiety drug)
39
Ka=1/kd
Okay slide 17
40
Why does HSA bind many drugs and synthetic drugs
It’s like a drug and fatty acid buffer If you have a drug that has a high response rate to the dose HSA binding allows for the drug to diffuse and transport through the blood so we don’t get high dose response rate and high dose in one area
41
What is propofol
It’s a drug that is very dangerous because it has a high dose response rate and doesn’t bind to HSA Killed Micheal Jackson
42
Where is the third drug binding site in HSA What binds there
The 1B domain Billiverdin and hemin bind here
43
Is there competition for drugs at the different binding sites of HSA What types of interactions do these binding sites have
Yes Allosteric interaction (binds one then the other with higher affinity)
44
Where is drug binding site 1 located What about 2
Domain 2a Domain 3a
45
If a drug is hydrophobic it’ll bind to
Fatty acid binding sites
46
What is methotraxate How can it get displaced and what’s the result
Used as a drug in treating cancer in high doses and rheumatoid artheritis in low doses NSAIDS (naproxen) displace methotrexate and increase free methotrexate levels in the plasma (toxic competition)
47
How can cancer tumours benefit with HSA How do we stop this
They bind HSA and use it as a source of nitrogen We can bind anti cancer drugs to HSA so the the tumour attached to HSA dies Not specific tho, just randomly binding hsa
48
What another example of coupling drug to HSA
The one free cysteine (cys34) get drugs attached to it
49
How many cys in hsa How many disulfide binds What does this mean
34 17 One free cys (cys 34)

Bcem 431 (33 decks)

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