Lecture 2

Question 1

MUC =

Answer 1

Mucins in humans

Question 2

Muc =

Answer 2

Mucins in mice

Question 3

What is the major mucin in the small intestine?

Answer 3

MUC2

Question 4

What happens to aspirin when it goes into the stomach?

Answer 4

When combined with the acid it becomes uncharged and so it can cross the cell membrane

Question 5

What happens do ethanol when it is in the stomach?

Answer 5

It has its own charge and so it can be absorbed across the stomach

Question 6

What type of organ is the stomach?

Answer 6

It is a non-absorptive organ

Question 7

What types of mucin are absorbed in the stomach?

Answer 7

MUC5AC and 6

Question 8

What is the MW of a mucin polymer?

Answer 8

2million MW and when it forms complexes the MW is 10 million

Question 9

What is the structure of a mucin polymer?

Answer 9

Has a variable tangent repeat, a density glycosylated region, Globular domains and disulphide bridges linking subunits into polymers

Question 10

What are VNTR also called?

Answer 10

An STP region as they contain serine, theronine and proline

Question 11

What can attach to the STP region?

Answer 11

Carbohydrates can attach

Question 12

What are the regions between the VNTR?

Answer 12

They are exposed to proteolytic enxymes

Question 13

How do the mucin polymers polymerise?

Answer 13

By disulphide brides - can polymerise at the C and N terminal

Question 14

What needs to happen in order for mucin to form a gel?

Answer 14

Mucin needs to be polymerised

Question 15

What can the gaps in between the VNTR be degraded by?

Answer 15

Can be degraded by pepsin

Question 16

What ends up in the colon?

Answer 16

A soluble mucin glycoprotein that can’t be further digested by proteinase, so it wont be able to form a gel.

Question 17

What type of balance is needed in the stomach?

Answer 17

A dynamic balance - between secretion and the pepsin that is degrading the mucus from the surface - a dynamic balance is needed to maintain the thickness of the mucus

Question 18

What is pepsin?

Answer 18

It is a damaging agent and is found in the stomach in gastric juice

Question 19

What pepsin subgroups are found in gastric juice in humans?

Answer 19

A and C

Question 20

Can pepsin diffuse through mucus?

Answer 20

No because it is too large

Question 21

How does pepsin get to the cell surface?

Answer 21

Mucus would need to be digested

Question 22

What pepsin is the most negatively charged?

Answer 22

Pepsin 1

Question 23

What type of pepsin is the least negatively charged?

Answer 23

Pepsin 6

Question 24

What are two ways to separate pepsins?

Answer 24

Gel electrophoresis and HPLC

Question 25

What are the main pepsins in gastric juice?

Answer 25

5,3,1- and they are separated by anion exchange

Question 26

What happens to pepsin during reflux?

Answer 26

Some of the gastric juice will end up on your larynx, this will be neutralised but the pepsin will be stuck to the larynx. Th next reflux there is a drop in pH, as the pepsin that got stuck is already sitting there

Question 27

When is pepsin activated?

Answer 27

When there is a change in pH

Question 28

What covers the active site of pepsin?

Answer 28

A lid which is formed by the n terminal

Question 29

What are the two points of cleavage on the pepsin molecule?

Answer 29

16 and 17 and 44 and 45

Question 30

Where does pepsin cleave?

Answer 30

Between 2 hydrophobic amino acids

Question 31

What is the difference between pepsin and pepsinogen?

Answer 31

Pepsin has a bit missing, and end chopped off

Question 32

What happens to the lid at a pH of 5?

Answer 32

To is held away from the active site, and it is held up by salt bridges or charge-charge interactions

Question 33

What happens above pH5?

Answer 33

Histamine, lysine and arginine and +ve charged and aspartate and glutamate are -ve charged

Question 34

What happens when the pH decreases below pH5?

Answer 34

Aspartate and glutamate will get protonated - they wont be charged anymore, they have lost the negative charge

Question 35

What happens when the bridge is lost? Below pH5

Answer 35

The lid will drop into the active site, the active site becomes activated and cleaves the end terminal between 1-16 amino acids

Question 36

What can propepsin interact with?

Answer 36

Other propepsin molecules or full active pepsin molecules

Question 37

What is the pepsin structure?

Answer 37

N terminal is slightly different to the c terminal, a central valley is where the active site is held

Question 38

What is pepsinogen structure?

Answer 38

The N and C terminals are almost identical

Question 39

What does the active site in the pepsin structure rely on?

Answer 39

Relies on two aspartate residues (32 and 215)

Question 40

What is the active site residue reliant on?

Answer 40

Relies on one aspartate being ionised and the other being protonated

Question 41

Can you reform pepsinogen from Pepsin?

Answer 41

No - because pepsin has the N terminal chopped off

Question 42

When does pepsin denature?

Answer 42

At pH8

Question 43

What is the structure/ stability of pepsin at pH 8?

Answer 43

Long and denatured, the molecule has been unfolded

Question 44

What happens if pepsin was to be refolded after it had been denatured?

Answer 44

It won’t fold properly because the n terminal is not in the right shape, instead of a valley for the active site there is a an open plane - you can reactivate pepsin once it has been denatured

Question 45

How long is pepsin in humans?

Answer 45

47 amino acids long

Question 46

Why is pepsin a good antimicrobial?

Answer 46

Because it will digest the bacteria. The bits cleaved off the pepsin will also have good antimicrobial activity