Membrane proteins

Question 1

what is the function of the membrane

Answer 1

1. The plasma membrane separates the cellular contents from the outside
2. The internal membranes separate the contents of organelles from the rest of the cell
3. Control the passage of molecules in and out of the cell

Question 2

what happens if there are no membranes

Answer 2

No membranes, no gradients, no energy

Question 3

What are the variation of the membranes

Answer 3

• Typical membrane = 50% protein, 50% lipid
• Mitochondria = 75% protein, 25% lipid
• Myelin sheath = 25% protein, 75% lipid (for insulation)

Question 4

what does the protein content part of membranes allow for

Answer 4

he protein component is what accounts for its selective permeability – the gateways into cells

Question 5

what are the different examples of protein in the body

Answer 5

• Different proteins – e.g. single/multiple alpha helices, rolled up beta sheets, glycosylated membrane lipids that do not cross membrane but are attracted to membrane because they’re lipidated - anchors that they insert into bilayer, some also associate with bona fide membrane proteins but do not themselves attach

Question 6

what are the 3 main types of lipidation

Answer 6

• 3 main types of lipidation: myristoyl, palmitoyl, farnesyl anchors.
Longer chain =more stable. Used to recruit/detach proteins from membranes

Question 7

apical and basal membranes contain….

Answer 7

different proteins,

- tight junctions enable this

Question 8

what are the different types of membrane proteins and give examples of them

Answer 8

• Channels – opens and allows flow, often very selective for particular ion (Cytic Fibrosis Transmembrane Regulator – effectively a chloride channel)
• Transporters – allow transport against the concentration gradient (ABCB1 hydrolyses ATP and pumps things out of cells e.g. drugs). Can concentrate a solute on one side of the membrane
• Integrins - involved in adhesion – attach cells to ECM
• Adhesins/connexins – attach cell to cell (connexin 26 – allows K+ ion flow between cochlear cells – mutations cause deafness)
• Receptors – transmit signals across the membrane (FGFR3 – bound to fibroblast growth factor receptor – tyrosine receptor kinase. Mutations cause achrondroplasia (short stature). Can either endocytose the ligand or the ligand will cause a conformational change in the receptor, causing a signal inside cells
• Enzymes – catalyse reactions (phospholipase C – recruited to membrane. influences cell behaviour. protein kinase C activation and stimulates Ca2+ release from the ER)

Question 9

what is passive diffusion

Answer 9

• Passive diffusion is when molecules than diffuse DIRECTLY through the phospholipid bilayer

Question 10

what is facilitated diffusion

Answer 10

• Facilitated diffusion is when a molecule moves through the phospholipid bilayer using a membrane protein but NO ATP
• Net flux depends on the electrochemical gradient
• Movement will stop will equilibrium is reached

Question 11

given an example of facilitated diffusion

Answer 11

• Moves ions such as Na+ and larger molecules such as glucose by Glut1-7

Question 12

describe Vmax and Km in facilitated diffusion

Answer 12

• Has Vmax where Km is at half Vmax and a low Km means high affinity transport
• Vmax is the maximum rate of reaction when the enzyme is saturated with substrate
• Vmax is the maximum rate of reaction when the enzyme is saturated with substrate
• Km is the concentration of substrate which permits the enzyme to achieve half Vmax. An enzyme with a high Km has a low affinity for its substrate, and requires a greater concentration of substrate to achieve Vmax

Question 13

what is active transport

Answer 13

• Active transport is when a molecule moves through the phospholipid bilayer using a membrane protein and ATP. Moves AGAINST the concentration gradient
- uses transporter proteins

Question 14

what are the type of active transport

Answer 14

primary and secondary

Question 15

what can passively diffuse

Answer 15

• Small and polar so they can penetrate the bilayer
• Small and non polar
• Polar – uncharged can cross
  The larger the molecule the less likely they are to move through the bilayer

Question 16

describe the electrochemical gradient

Answer 16

• Molecules move from an area of high concentration to an area of low concentration.
• They also move according to charge.
• In this example they move from an area that is very positive to an area that is less positive (more negative).

Question 17

Describe channel proteins

Answer 17

• This is a continuous pore through the membrane
• Use facilitated diffusion to move molecules from an area of high to low concentration through a membrane protein
• Uses charge to be selective for example a channel may be negatively charged to attract a positively charged solute and repel a negatively charged solute to allow only certain molecules to enter the cell
• Move large amounts of solutes -high bulk flow
• Regulated
• Charge across the membrane influences efficiency of diffusion – e.g. negative on the inside enhances gradient

Question 18

describe the action of passive membrane transporters

Answer 18

1. Solute binds to the binding sites on the outside of the membrane
2. The solute binding causes transporter to change shape (conformational change)
3. Solute can now move into the cell
   - Movement is dependent on the electrochemical gradient, - solutes must move from a high concentration to a low concentration
   - Low capacity

Question 19

describe the action of active membrane transporters

Answer 19

1. Solute binds to binding sites on the outside of the membrane.
2. This causes ATP to bind to the transporter and split to ADP and phosphate.
3. The energy created is used to change the shape of the transporter (conformational change)
4. The solute can move into the cell
   - Movement is dependent on ATP so can move against the electrochemical gradient

Question 20

describe primary active transport

Answer 20

• ATP hydrolysis provide the energy to move the molecular against the electrochemical gradient

Question 21

what is an example of primary active transport

Answer 21

• E.g. Na+/K+ ATPase
• Na+/K+ pump maintains the resting membrane potential across the cell membrane. It moves three sodium ions out of the cell for every two potassium ions brought in meaning that the outer membrane remains mainly positive.

Question 22

what is secondary active transport

Answer 22

• The energy stored in the electrochemical gradient of a solute moving down its electrochemical gradient is used to transport another solute move actively against its concentration gradient

Question 23

describe an example of secondary active transport

Answer 23

• E.g. SGLT1
  SGLT1 (Sodium glucose linked transporter) found in the intestinal epithelium. Uses the absorption of sodium down its concentration gradient to transport glucose into cells against the concentration. This means that all glucose possible is absorbed from food and none is lost in the stool
• Both solute and ion bind at the same time, transporter changes conformation, free energy released as the contransported ion moves down its electrochemical gradient, can drvie the solute up its electrochical gradient- secondary active transport

Question 24

what is co transport

Answer 24

• This is a form of secondary active transport

Question 25

what are the two types of cotransport

Answer 25

symport and antiport

Question 26

what is antiport

Answer 26

opposite directions (so one is pumped out while one is pumped in) – Na+/K+ ATPase

Question 27

what is symport

Answer 27

pumped in the same direction (they are both pumped inwards) SGLT1

Question 28

Describe the receptor mediate endocytosis

Answer 28

• Particles bind to the receptor on the cell surface membrane
• The membrane bends and folds over on itself (invaginates) and forms a vesicle.
• Particles contained in that vesicle can be transported around inside the cell.
• Solute binds to the receptor on the surface and internalises the complex by endocytosis

Question 29

what is an example of receptor mediate endocytoiss

Answer 29

• Ldl receptor binds through extracellular domain, internal domain changes conformation, recruits clathrin
• Causes membrane to invaginate inti liposome and close around the protein with the attached ligand
• E.g. LDL receptor taking up LDL , harvest choestrol

Question 30

describe glucose transport

Answer 30

• Secondary active symport
• Glucose brought in via SGLT1 in the apical/luminal membrane with Na+
• Glucose diffuses (therefore passive) out Glut2 in the basal membrane into the extracellular fluid and enters the bloodstream down its conc gradient via facilitated difusion
• Sodium pumped out of cell and potassium pumped in by Na+K+ATPase in basal membrane which creates a lower concentration of Na+ inside the cell so drives the facilitated diffusion of sodium into the cell, bringing with it glucose

Question 31

describe progressive familia intrahetic cholestasis

Answer 31

• Cholestasis: When bile cannot flow from the liver to the duodenum
• PFIC: A rare fatal disease of childhood that causes:
• Jaundice, itchy skin, failure to thrive, hepatosplenomegaly and dark urine.
• This is caused by mutation in these two transporters:
• ABCB4
• ABCB11
• ABCB4 is also known as MDR3. MDR3 transports phosphatidyl choline into the bile.
• ABCB11 also known as BSEP is a type of bile salt transport pump

Question 32

describe familia hypercholetrolemia

Answer 32

• A recessively inherited disease which causes high cholesterol.
• It is caused by a deficiency in receptor mediated endocytosis.
• No low density lipoproteins are taken into cells so stay in the blood increasing blood cholesterol levels.
• This is caused by deletion of the clathrin domain on the low density lipoprotein receptor.
• Clathrin is the component of the receptor that allows it to invaginate and form a vesicle

Question 33

what kind of mutation is cystic fibrosis

Answer 33

• An autosomal recessively inherited disease caused by mutations in the channel protein CFTR.

Question 34

where is the protein channel CFTR found

Answer 34

• Found in the plasma membrane of epithelial cells of the lungs pancreases and intestine

Question 35

what does the CFTR mutation cause and how do you treat it

Answer 35

• CFTR – Cystic fibrosis transmembrane regulator
• Type of channel protein that transports Cl- outside of the cell
• Mutation means that the channels are not brought the cell membrane.
• Treated with Lumacaftor and Ivacafor

Question 36

what does cystic fibrosis cause and how does it cause it

Answer 36

• Chloride thins mucus secretions from cells. It does this by inducing the flow of Na and H20 out of cells by creating an electrochemical gradient. As a result the mucus becomes more watery and thinner. If the CFTR proteins are not there no chloride ions can enter the secretions causing them to become thick. This affects cells in the intestines, pancreas, liver kidney, sweat gland, reproductive tract and lungd.

Question 37

how is cystic fibrosis treated

Answer 37

• Lumacaftor helps the mutated CFTR (ΔF508) to fold and be transported to the cell surface membrane where it can work.
• Ivacaftor is a gene therapy that acts on CFTR channel to improve transport of chloride ions.