CHO metabolism

Question 1

What type of glucose transport proteins are located on the lumen of epithelial tissues?

Answer 1

Sodium symporters - energy is required to move glucose up its concentration gradient into the cell so its coupled with Na+ import

Question 2

What are the two main ways to import glucose into cells?

Answer 2

1. sodium symport

2. Facilitated glucose transporters (moves glucose down its concentration gradient)

Question 3

What would be the effect of a non-functional Na+/K+ ATPase on intracellular glucose concetrations?

Answer 3

• It Na+/K+ ATPase were ineffective the gradient of Na+ would be reduced
• This would reduce the amount of energy released by Na+ import
• Without sufficient energy symport of glucose into the cell would not be achieved

Question 4

Where can GLUT1 be found and what are its characteristics?

Answer 4

• Found in ALL mammalian tissues
• Km = 1 mM (High Affinity for glucose)
• Responsible for basal glucose uptake

Question 5

Where can GLUT2 be found and what are its characteristics?

Answer 5

• Liver and ß cells of the pancreas
• Km = 15 - 20 mM (Low Affinity)
• only kicks in after carb rich meal

Question 6

Where can GLUT3 be found and what are its characteristics?

Answer 6

• Found in ALL mammalian tissues
• Km = 1 mM
• Responsible for Basal Glucose uptake

Question 7

Where can GLUT4 be found?

Answer 7

• Muscle and Fat cells

- Km = 5 mM (Medium Affinity)

Question 8

What type of GLUT is specific for liver and ß-cells of the pancreas, and what is it job in these tissues?

Answer 8

Pancreas:
- plays a role in regulating insulin

Liver:
-Removes XS glucose from the blood

Question 9

What type of GLUT is associated with neuronal cells?

Answer 9

GLUT3

Question 10

What type of GLUT increases in muscle cells as a result of endurance training?

Answer 10

GLUT4

Question 11

What type of GLUT is upregulated by the presence of insulin?

Answer 11

GLUT2 and GLUT4

Question 12

Explain the effect of GLUT2 uptake of glucose in ß-cells of the pancreas.

Answer 12

1. Glucose enters the cell and enters glycolysis or oxidative phosphorylation producing ATP
2. ATP/ADP rises
3. Increased ATP binds to K+ channel causing it to close
4. With K+ channel closed the cell depolarizes and Ca2+ voltage-dependent channels open up releasing Ca2+ into cell
5. Elevated Ca2+ causes fusion of Insulin vesicles via vSNARE and tSNAREs
6. Insulin is released (note: insulin has a feed-forward effect on GLUT2 expression in cell)

Question 13

What type of GLUT is expressed on red blood cells?

Answer 13

GLUT 1

-NOTE: RBCs are unique in that they are very glucose dependent because they do oxidative phosphorylation

Question 14

Why does the liver need GLUT2 to be its major glucose importer?

Answer 14

• GLUT2 has a high Km (low affinity), so it will only open to let glucose in under high concentrations.
• This is important because the liver is a glycogen storage organ, if glucose could easily enter then it would get trapped as glycogen and be unavailable to the rest of the body.

Question 15

How does upregulation of GLUT4 by insulin work?

Answer 15

1. Pre-existing endosomes containing insulin are in the cells of muscle and adipose tissue
2. Insulin binds to the receptors on the cell surface and the vesicles containing the GLUT4 transmembrane protein become a part of the cell membrane

Question 16

What are the steps that are taken in GLUT proteins that allow for glucose to be transported through the transporter?

Answer 16

1. Glucose binds to the GLUT protein via interactions with glucose hydroxyl
2. Transport protein undergoes a conformational change to open the flaps and let glucose through
3. Transport protein closes as glucose is released to the other side of the membrane

Question 17

What causes lighteadedness or dizziness in hypoglycemia?

Answer 17

Decreased supply of glucose to the brain

Question 18

Why does blood glucose drop faster in the brain than in other tissues?

Answer 18

• The BBB is tightly regulated, the only way through the brain endothelial cells is through Na+/Glucose symporter on lumen side and GLUT1 or 3 transporter on the side with cerebrospinal fluid

this is caused by:

1. Very effective tight junctions
2. Narrow Intercellular spacing
3. Lack of pinocytosis
4. Continuous basement membrane

Question 19

In non-neuronal tissues, what features allow increased flow of glucose across the endothelial lining?

Answer 19

1. No tight Junctions
2. Sometimes wide intercellular gaps
3. Pinocytosis
4. Discontinuous basemement membrane
5. glucose can diffuse between cells and into interstitial fluid

Question 20

How does pinocytosis increase intracellular glucose?

Answer 20

• its the non-specific import of particles so with each vesicle imported there is a good chance that among the imported particles some will be glucose

Question 21

What are 3 pathways that use glucose 6-phosphate (G6P)?

Answer 21

1. Glycolysis —> ATP
2. Pentose Phosphate Pathway (NADPH)
3. Glycogen Synthesis

Question 22

T or F: Insulin acts as upregulator both of GLUT2 and Glucokinase?

Answer 22

True

Question 23

T or F: the reaction of glucose 6-phosphatase is irreversible?

Answer 23

True

Question 24

T or F: glucose-6-phosphatase can be found in all tissue types?

Answer 24

FALSE, its only found in the liver and kidney

Question 25

What are the 4 important domains of glucose-6-phosphatase and what are their functions?

Answer 25

T1 - Puts G6P into ER lumen
Phosphatase - remove phosphate form G6P, leaving glucose
T2 - exports phosphate to cytosol
T3 - exports glucose to cytosol

Question 26

Hexokinase…
Distribution?
Km?
Regulation?

Answer 26

• All cells
• Km = 0.1mM or lower
• inhibited by G6P (this is feedback inhibition)

Question 27

Glucokinase…
Distribution?
Km?
Regulation?

Answer 27

• Liver and ß-cells of the pancreas
• Km = 10-20 mM (far below fasting glucose of ~5 mM)
• Induced by insulin (not affected by G6P accumulation)

Question 28

Why would you see an increase in glucose-6-phosphatase activity around 2 hours after eating a meal?

Answer 28

• at this point blood glucose begins to drop back to normal levels so glycogen needs to be mobilized so that it can be used by other tissues. This requires G6Pase.

Question 29

Why does Dr. Cox’s diabetic tennis friend get light headed during tennis?

Answer 29

• Exercise depletes blood glucose and his insulin pump releases insulin that stimulates his fat and muscle to sequester glucose
• this leaves his brain in a glucose depleted state