Membrane Structure and Transport

Question 1

describe lipid rafts, what the are rich in and what they facilitate

Answer 1

• An area with unique proteins and lipid composition which separates them from other fluid membrane areas
• Lipid rafts are rich in:
  
  • Cholesterol
  • Glycosphingolipids
  • Sphingomyelin
• Lipid rafts can facilitate signal transduction and virus infection

Question 2

describe the composition of the leaflets in the PM

Answer 2

• The outer leaflet contains
  
  • mainly PC
  • sphingomyelin
  • some PE
  • glycosphingolipids
• The inner leaflet contains
  
  • mainly PE
  • some PC
  • PS
  • PI
  • PIP2
• Glycolipids and glycoproteins are only found in the outer layer and form a glycocalyx (2-10% of the weight)

Question 3

what determines the fluidity of the PM

Answer 3

Fluidity of the PM is determined by the FA composition of phospholipids and also by the amount of free cholesterol

Question 4

what role does cholesterol play in the PM and where is it in the PM

Answer 4

• Cholesterol is present in both layers
• Cholesterol decreases the fluidity of the PM close to the polar head groups and increases the fluidity inside of the bilayer
• Cholesterol binds in the space that is generated by cis-double bonds of FA
• Cholesterol prevents drastic changes in fluidity due to high or low temps

Question 5

how does temp affect fluidity of PM

Answer 5

• Low temp: the fatty acyl groups are stiffer and cholesterol increases the membrane fluidity by separating them and prevents close packing
• High temp: the fatty acyl groups are more fluid and cholesterol decreases the membrane fluidity with its steroid ring system and slows down their movement

Question 6

describe the composition of other biomembranes

Answer 6

• Membranes inside the cell do not contain cholesterol. The fluidity is mainly regulated by the FA composition
• The inner mitochondrial membrane contain cardiolipin which is not found in other membranes
• Lipoprotein membranes are composed of a phospholipid monolayer which allows transport of nonpolar lipids (TAGs and cholesteryl ester) in the blood and lymph. Free cholesterol is found in monolayer

Question 7

what determines membrane fluidity?

Answer 7

it is determined by the FA found int he polar lipids in the membrane

Question 8

why is the FA composition especially important for intracellular membranes?

Answer 8

This is because intracellular membranes have little or no cholesterol is help regulate fluidity

Question 9

what characteristics of phospholipids make the membrane more fluid? Name 2.

Answer 9

Shorter FA and unsaturated fatty acids make the membrane more fluid. Especially arachidonic acid (20:4; w-6) and DHA (22:6, w-3) increase fluidity

Question 10

glycerophospholipids contain normally ____ fatty acid at position 1 and _____ fatty acid at position 2

Answer 10

1. Saturated
2. Unsaturated

Question 11

transport of glucose into cells: name the sodium independent glut transporters, facilitated diffusion transport

Answer 11

• GLUT 1: brain, RBC
• GLUT 2: liver, kidney, B-cells of pancreas, intestine
• GLUT-3: neurons
• GLUT 4: muscle and fat
• GLUT 5: intestine, seminal vesicles

Question 12

transport of glucose into cells: name the sodium-dependent glucose transporters, secondary active transport

Answer 12

SGLT-1: intestine (epithelial cells at the luminal side)

SGLT-2: kidney (epithelial cell in renal tubules)

Question 13

High affinity GLUT transporters are

Answer 13

GLUT1, GLUT3 and GLUT4

Question 14

Low affinity GLUT transporters are

Answer 14

GLUT2 and GLUT5

Question 15

describe the glucose uptake with GLUT1 and GLUT3

Answer 15

The uptake with GLUT1 and GLUT3 remains at a constant rate with normal and lower blood glucose concentrations

GLUT1 is abundant in RBC, and it is also found in the blood-brain barrier as well as in the kidneys

GLUT3 is dominant in neurons and brain

Question 16

which GLUT transporter is insulin-dependent?

Answer 16

• GLUT4 is insulin-dependent.
• GLUT4 is abundant in fat cells, skeletal muscle and the heart
• Insulin mobilizes the transport of GLUT4 from the endosome to the PM. Once the GLUT4 arrives at the PM, it allows the influx of blood glucose into the cell
• Insulin injection can lead to hypogylcemia due to rapid uptake of blood glucose into skeletal muscle and fat cells via the mobilized GLUT4

Question 17

what mobilizes GLUT4?

Answer 17

Insulin and vigorous exercise of the skeletal muscles

Question 18

describe the efficiency and rate of glucose transport with GLUT2

Answer 18

GLUT2 (low-affinity transporter) is capable of transporting large amounts of glucose molecules at a high glucose concentration (1/2 maximal transport of glucose is reached at 10-15 mmol/L)

Question 19

where is GLUT2 found?

Answer 19

• Intestinal mucosal cells and facilitates release of dietary sugars into portal vein
• Hepatocytes: GLUT2 takes up glucose when there are high levels of dietary sugars. During fasting, glucose is released into the blood from hepatocytes with the concentration gradient
• Renal tubular cells for the re-uptake of glucose
• B-cells of pancreas: GLUT2 transports large amounts of glucose and is used to “measure” high blood glucose levels

Question 20

summarize the transport rates for GLUT3, GLUT4 and GLUT2 related to fasting blood glucose levels

Answer 20

Question 21

why is GLUT5 different?

Answer 21

• GLUT5 prefers the transport of fructose over glucose
• GLUT5 transports mainly dietary fructose. Dietary glucose only at very high level of glucose concentration

Question 22

where is GLUT5 found?

Answer 22

• Found in the intestinal mucosal cells on the luminal side of the intestinal membrane
• GLUT5 is also found in seminal vesicles which release fructose into semen. The seminal vesicles use blood glucose to form fructose to supply the energy metabolism of sperm cells

Question 23

describe problems that arise from GLUT1 deficiency and what it causes

Answer 23

• Deficiency of GLUT1 leads to microcephaly and epilepsy-like seizures in the first few months of life
• As individuals mature they develop the follwing:
  
  • Ataxia
  • Delayed psychomotor development
  • Movement disorders
  • Impaired speech

Question 24

how does the Na/K/ATPase pump work?

Answer 24

By cleaving ONE ATP, 3 Na+ are pumped out and 2 K+ ions are pumped into the cell.

Question 25

describe what SGLT1 is

Answer 25

* It is a symporter that transports Na ions and glucose or galactose into the intestinal mucosal cell * The transport of glucose or galactose is performed against a gradient and the Na/K ATPase has to be active

Question 26

what are ABC transporters?

Answer 26

* ATP Binding Cassette * In eukaryotes, ABC transporters allow the active transport of molecules from the cytosol to the extracellular space: * This process needs hydrolysis of ATP * The transported molecules are often lipids or lipid-related compounds * Example: liver releases bile salts, cholesterol and conjugated bilirubin into the bile ducts using ABC transporters

Question 27

what is the CFTR?

Answer 27

* It is a gated channel with a pore for chloride ions. This pore can be opened or closed following a stimulus. * Although a few molecules of ATP are cleaved the transport is considered PASSIVE TRANSPORT which leads to many chloride ions flowing through the open channel

Question 28

describe the CFTR

Answer 28

* Cystic fibrosis transmembrane conductance regulator is a special ABC transporter which is more a chloride ion channel than a transport protein * CFTR does NOT pump Cl ions--they flow with the gradient once channel is opened

Question 29

name the epithelial cells where CFTR is present

Answer 29

* Reproductive ducts * Intestinal lumen * Pancreatic ducts * Airway ducts * Skin

Question 30

describe the structure of CFTR

Answer 30

* CFTR consists of 2 transmembrane domains * 2 groups of 6 alpha helices * Each is connected to an ATP-binding site * One regulatory domain of the channel is intracellular

Question 31

what are symptoms of deficient CFTR?

Answer 31

* In the newborn the early sign are salty skin * Later in life * Recurrent lung infections * Chronic pancreatitis * Steatorrhea (abnormal amount of fat in feces)

Question 32

describe the normal process of sweating

Answer 32

* In a typical epithelia cell, Cl ions are first accumulated inside the cell which generates a higher Cl ion concentration than in the extracellular space * These negatively charged Cl ions are then released with the gradient into the extracellular lumen via CFTR, where sodium ions and water follow * In the sweat gland coil, large amounts of Na and Cl ions are released along with water * The sweat formed in the coiled section of the sweat gland has a higher concentration of NaCl than the sweat actually released * In the secretory duct, the Cl ions flow back into epithelial cells via CFTR. * This allows the salvage and re-uptake of Cl ions by the epithelial cells using passive transport (with graident)