Lecture 4: Specialized membrane proteins

Question 1

What are the two types of cell membrane proteins?

Answer 1

Integral membrane proteins

Peripheral membrane proteins

Question 2

Integral membrane proteins

Answer 2

Integral membrane proteins are associated with one or both layers of the
lipid bilayer membranes

Question 3

Peripheral membrane proteins

Answer 3

associated peripherally with the cell membrane

Question 4

How are integral membrane proteins associated to the membrane?

Answer 4

One of the lipid bilayers with a covalent lipid linker

One of the lipid bilayer with a non-covalent lipid linker

Or with an integral protein

Question 5

Functions of membrane proteins

Answer 5

Pores: to allow passage of metabolites or nutrients.

Ion channels: for intake and output of electrolytes.

Transporters: to allow the movement (entry and exit) of molecules Enzymes: to catalyze reactions.

Receptors: to receive and propagate signals.

Cell adhesion proteins: to connect cells for cellular communications.

Structural proteins: to give mechanical properties to cells.

Question 6

What are defects in the function of membrane proteins associated with?

Answer 6

Diseases

Question 7

Why are integral membrane proteins difficult to purify?

Answer 7

They have significant hydrophobic regions designed to interact with the lipid membrane bilayer.

Question 8

What types of secondary structures do integral membrane proteins have?

Answer 8

Alpha helical (coiled) and beta sheets

Most integral membrane proteins use one or more alpha sheets. But the can also form beta pleated barrels

Question 9

What does polytonic mean?

Answer 9

Transmembrane, span entire membrane

Question 10

What does monotonic mean?

Answer 10

Integral protein that only associates with one leaflet of the bilayer

Question 11

How do monotonic integral membrane proteins interact with the membrane?

Answer 11

1. amphipathic alpha helix
2. hydrophobic loops
3. a covalently attached lipid group
4. electrostatic or ionic interactions with membrane phospholipids

See figure

Question 12

Specific functions of integral membrane proteins

Answer 12

allow cells to interact with and communicate with their environment.

gatekeepers of the cell — entry and exit route for ions, nutrients, waste products, and proteins.

Receive and transmit signals from both long range (hormones, growth signals) and short range (cell: cell communication)

Question 13

Transport of small molecules and inorganic ions across the membrane

Answer 13

See table

Question 14

What is facilitated diffusion?

Answer 14

passive movement of molecules/substrates across the cell membrane by a carrier/transporter protein that does not require an external energy source (i.e. metabolic energy/ATP) directly or indirectly.

Question 15

What molecules use facilitated diffusion?

Answer 15

Water soluble molecules (ex: glucose)

Question 16

Which way does substrate move in facilitated diffusion?

Answer 16

Down the concentration gradient

Question 17

What type of proteins does facilitated diffusion require?

Answer 17

Integral transmembrane proteins

Question 18

What kind of interaction occurs between the solute and the carrier in facilitated diffusion?

Answer 18

substrate has to bind specifically and non-covalently to the carrier

Question 19

Rate of diffusion during facilitated diffusion

Answer 19

carrier is saturable; and the rate of diffusion is directly proportional to the concentration gradient.

Question 20

How can glucose carriers be inhibited?

Answer 20

Glucose analogs

Question 21

How are glucose transporter isoforms different from each other?

Answer 21

Where they are located

Affinity for glucose may differ

Activity may depend on insulin

Question 22

Regulation of GLUT4 in membrane

Answer 22

In the absence of insulin, the GLUT4 transporters are located inthe intracellular vesicles just inside the plasma membrane

In the presence of insulin, it binds to the insulin receptor and initiates a signal transduction cascade; one result from this cascade is that the GLUT4 containing vesicles fuse with the plasma membrane, allowing it to function.

Question 23

Clinical implications of GLUT4

Answer 23

A mutation at amino acid position 383 has been found in a small number of patients with non-insulin dependent diabetes

A fungal mycotoxin, cytochalasin B, can inhibit both GLUT1 and GLUT4 (among other affects)

Indinavir, an HIV protease inhibitor, is also an inhibitor of GLUT4, leading to metabolic side effects seen in many patients taking this dru

Question 24

What is the sodium-glucose symport essential for?

Answer 24

sodium dependent glucose transport in the apical membrane of the small intestine (SGLT1) or the apical membranes in the proximal tubules of the kidney (primarily SGLT2, small amount of SGLT1)

Question 25

What do sodium- glucose symports need to function?

Answer 25

require the Na+ gradient generated by the Na+-K+-ATPase on the basolateral membrane

Question 26

Efficiency of sodium-glucose symports

Answer 26

extremely efficient transporters

100% of the glucose filtered in the kidney is reabsorbed from the filtrate via sodium co-transport

Question 27

A model for sugar transport across the enterocyte showing the brush-border SGLT1 and GLUT5 transporters and the basolateral Na+-K+-pumps and sugar transporter GLUT2.

Answer 27

See figure

2 types of glucose transporters working in concert

Question 28

What causes defects in SLC5A1?

Answer 28

congenital glucose/galactose malabsorption (GGM)

characterized in the first few weeks of life in infants by severe diarrhea and dehydration, which are usually fatal unless glucose and galactose are eliminated from the diet.

Question 29

How should diarrhea be treated?

Answer 29

Oral rehydration therapy with solutions of glucose and salt is an extremely important treatment for acute diarrhea (esp. with cholera)

Glucose and sodium are transported into the enterocytes and then to the blood stream; water follows by osmosis, leading to rehydration

Question 30

What is essential for the functioning of transport proteins?

Answer 30

Conformational changes