Lecture 4

Question 1

What does the cell membrane consist of?

Answer 1

Double layer of amphipatic molecules, proteins and carbohydrates.

Question 2

Name 6 ways a molecule can transport through cell membranes. What determine the transport?

Answer 2

1. Diffusion
2. Facilitated diffusion (Passive transport)
3. Ion channel (Passive transport)
4. Active transport
5. Endo-/exocytosis
6. Paracellular transport

The chemical properties determine the transport.

Question 3

What is the most important mechanism for transport of organic compounds through membranes?

Answer 3

Diffusion.

Question 4

What does the molecule take advantage of to be able to transport through the membrane by diffusion?

Answer 4

It take advantage of the fact that the membrane is not frozen, it is constantly moving which means molecules can slip through the holes created.

Question 5

What kind of molecules can pass through by diffusion? Can ions pass?

Answer 5

1. Small molecules (H2O, MeOH)
2. Large (M<1000) lipophilic (hydrophobic) molecules.

Ions can’t pass. They are small but they aren’t alone, they are usually surrounded by water.

Question 6

What is the 2 most important factors for a molecule to be able to use diffusion? What is the driving force for hydrophobic molecules?

Answer 6

Its size and hydrophilicity.

The driving force is the hydrophobic interior (?).

Question 7

If a molecule is hydrophobic, does it mean it’s lipophilic or lipophobic?

Answer 7

Hydrophobic (water hating)=Lipophilic (fat loving).

Question 8

What is facilitated diffusion?

Answer 8

It is the process involving a protein on the membrane and a specific recognition. The molecule bind to a specific binding on the protein and the protein then let it pass.

Question 9

For what kind of molecules is facilitated diffusion important?

Answer 9

It’s important for hydrophilic molecules that are not small enough.

Question 10

What gradient does facilitated diffusion follow?

Answer 10

The concentration gradient.

Question 11

What is ion channels?

Answer 11

It’s a passive tranport for small ions that take place by diffusion through pores (filtration).

Question 12

What gradient does ion channels follow?

Answer 12

The concentration gradient.

Question 13

What determines if the gate is opened or closed?

Answer 13

It depends on the environmental conditions.

Question 14

What is the difference between passive transport and active transport?

Answer 14

Passive transport goes from high to low conc. while active trasport can go from low to high conc.

Question 15

What is active transport?

Answer 15

Active transport can transport a molecule against the concentration gradient but it cost energy (ATP).

Question 16

What is the most important active transport in our bodies and what does it do?

Answer 16

It’s the Na/K pump. It makes sure we have more Na+ outside of the cell than inside and less K outside than inside. Because of the active transport, the pump can kick out 3 pcs of Na+ and let in 2 pcs of K+. The pump use 10-40 % of the cells ATP production.

Question 17

Why do we need the Na/K pump?

Answer 17

Because we need a high concentration of Na in order to bind glucose from the urine. The concentration of glucose is low, that’s why it’s important to keep a low concentration in the cell.

Question 18

What is endocytosis? What is exocytosis?

Answer 18

Endocytosis: the cell take in molecules from outside of the cell by engulfing them in a vesicle.
Exocytosis: the opposite, the cell takes molecules from within the cell and kick it out.

Question 19

What kind of substances can be moved by endo-/exocytosis?

Answer 19

Larger molecules, microorganisms and waste products that can’t be moved through the lipid bilayer.

Question 20

What is paracellular transport?

Answer 20

It’s the transport between the cells.

Question 21

Explain the difference in uptaking of glucose between birds and humans.

Answer 21

Humans: glucose-facilitated diffusion.
Birds: glucose is uptaken from the intestines, between the intestine celles.

In birds, glucose can’t stay inside very long which means it has to be uptaken efficently. The problem is that a toxic molecule may be uptaken aswell which is dagnerous. In humans it is the opposite, we have long intestines so the molecules can stay there much longer.

Question 22

How can we uptake chemicals from the environment? 3 ways.

Answer 22

1. Lungs
2. Intestinal tract
3. Skin

Question 23

How can chemicals be uptaken by the lungs?

Answer 23

In the lungs, we have alveoli (a bubble) which has no protection.

Question 24

In the gut/intestines, how are small and hydrophobic molecules absorbed?

Answer 24

By diffusion.

Question 25

In the gut/intestines, how are hydrophilic molecules absorbed?

Answer 25

By facilitated diffsuion or ion channels.

Question 26

In the gut/intestines, how are large molecules absorbed?

Answer 26

By endocytosis.

Question 27

How weel is insoluble molecules absorbed?

Answer 27

They are poorly absorbed.

Question 28

What kind of environment does the stomach have? And the intestines? Acid/base?

Answer 28

Stomach: acid
Intestines: base

Question 29

What is the function of the liver?

Answer 29

The liver transform some molecules into a useful form and then pump it back into the blood. Toxic molecules will also be metabolized and then excreted —> will go back to the intestines.

Question 30

In the stomach, where we have a low pH, will benzoic acid stay in a neutral and non-charged form or in its deprotonated form?

Answer 30

It will stay in its neutral, non-charged form since its deprotonated form is in basic environments.

Question 31

Is benzoic acid fast or slow in the stomach (low pH) and in the intestines (pH~7-8)?

Answer 31

Stomach: fast
Intestines: slow (will stay in the ionic form and ions aren’t easily absorbed)

Question 32

Aniline has a protonated form (R-NH3+) and neutral form (R-NH2). Which belong in the acid environment and which is in the basic environment?

Answer 32

R-NH3+: acid

R-NH2: basic

Question 33

Is aniline fast or slow in the stomach, respectively intestines?

Answer 33

Since NH3+ is in acid environments, like the stomach, and ions are difficult to absorb, it will be slow in the stomach. It will be fast in the intestines (pH~7-8) since the neutral molecule is basic.

Question 34

Are aromatic amines toxic?

Answer 34

Yes!

Question 35

Is absorption through the skin efficient? Why/why not?

Answer 35

No, it’s not efficient. The skin has tight layers of epidermis which means molecules won’t be easily diffused.

Question 36

How are molecules absorbed by the skin? Which molecules can be absorbed?

Answer 36

The molecule must penetrate the epidermis by diffusion before reaching the blood vessels. Small, nonpolar molecules can pass easily (e.g. MeOH, HgMe2).

Question 37

Name two molecules that can ease the permeability of the skin?

Answer 37

DMSO and water can swell the skin which allow other molecules to enter.

Question 38

What is xenobiotics?

Answer 38

Molecules that comes from the outside.

Question 39

What 3 factors does the distribution of xenobiotics depend on?

Answer 39

1. Solubility (lipophilic, hydrophilic)
2. Biological barriers (e.g. blood-brain barrier, “BBB”)
3. Transformations/Conversions

Question 40

What tissues does lipophilic molecules, hydrophilic molecules and Pb/F go to?

Answer 40

1. Lipophilic molecules go to lipophilic tissues (like brain, body fat)
2. Hydrophilic molecules go to blood, eyeballs, muscles
3. Pb, F go to the bones

Question 41

What is the blood-brain barrier (BBB)? What molecules does it restrict/allow access to?

Answer 41

BBB is a semipermeable border that restricts the passage of pathogens, solutes in the blood and large or hydrophilic molecules. It allows the diffusion of hydrophobic molecules (O2, CO2, hormones) and small non-polar molecules.

Question 42

What molecules can/can’t pass the BBB?

Answer 42

Can pass: 
- water, glucose
- small, lipophilic molecules
Can’t pass:
- large, hydrophilic molecules
- ions

Question 43

What does a high logP value mean? And a low value?

Answer 43

High (positive) value: higher hydrophobicity

Lower (negative) value: higher hydrophilicity

Question 44

What are the 3 most common excretion ways?

Answer 44

1. Via the kidneys (most important one)
2. Via the liver
3. Via the lungs

Question 45

What molecules use the kidneys as their major excretion route? Name one molecule.

Answer 45

Hydrophilic and small molecules, like penicillin.

Question 46

What’s the overall aim of metabolism?

Answer 46

To increase the water solubility in order for them to be excreted in the kidney. It’s the most efficient way to get rid of molecules.

Question 47

What’s the advantage and disadvantage of excretion via the liver?

Answer 47

Advantage: can get rid of large molecules (M>500).
Disadvantage: not very efficient.

Question 48

What is enterohepatic circulation?

Answer 48

It’s the circulation that extends the time that a lipophilic xenobiotic stay in the body. The molecule goes from the liver to the bile, then to the small intestine where it is absorbed by the blood and it’s transported back to the liver.

Question 49

What kind of compunds can be excretion in the lungs? What molecule has this as its major route?

Answer 49

Volatile compounds. Diethyl ether use this as its major route.

Question 50

How does excretion via the lungs work?

Answer 50

Volatile compounds can go from the blood to the air in the lungs and then be exhaled.

Question 51

Why can you do alcohol testing via blowing air into a machine?

Answer 51

Ethanol is polar but it doesn’t have a very high boiling point, which means there’s some excretion via the lungs but the major route is via the kidneys. Some ethanol is excreted via the lungs which is why you can test alcohol by blowing air.