M1: Energy Management & Glycolysis Part 1 L2

Question 1

Where does glucose get absorbed into the blood?

Answer 1

The small intestine

Question 2

Describe the process of glucose absorption from the small intestine into the blood.

(see L2.1 slide 11)

Answer 2

1. Glucose and Na+ get into the brush border epithelial cells through a symporter in the microvilli. This is secondary active transport from the gradient made by the Na+/K+ ATPase.
2. Glucose moves into the blood through a glucose uniporter. Passive transport.
3. sodium is pumped out of the enterocyte into the blood, in exchange for potassium (primary active transport through the Na+/K+ ATPase). This is to keep the Na+ concentration low in the cell, so that sodium from the intestinal lumen comes into the cell with glucose via the symporter (secondary active transport).

Question 3

Which cells uptake glucose in the pancreas?

Answer 3

Beta-cells

Question 4

At what glucose concentration does the pancreas release insulin into the blood?

Answer 4

[glucose] > 5.5 mM

Question 5

What is happening in a pancreatic Beta-cell when basal (between meals) [blood glucose] < 5.5 mM ?

(see L2.1 slide 13)

Answer 5

1. Blood glucose passively enters the Beta-cell through a Glut-2 transporter.
2. Basal glycolysis and ox-phos produces basal ATP.
3. The Potassium ATP channel (KATP) is open, and therefore pumping potassium out of the cell to maintain hyperpolarization of the membrane.
4. The insulin vesicles remain stable inside the cell, insulin is not released.

Question 6

What is happening in a pancreatic Beta-cell when stimulatory (after a meal) [blood glucose] > 5.5 mM ?

(see L2.1 slide 13)

Answer 6

1. Elevated levels of glucose are passively diffusing into the Beta-cell through the Glut-2 transporter.
2. Glycolysis and ox-phos produce an elevated level of ATP.
3. The elevated level of ATP inhibits the KATP channel which no longer allows potassium to exit the cell, therefore the membrane depolarizes.
4. there is a high concentration of calcium on the outside of the cell that enters the cell when it is depolarized. This induces vesicular release of insulin into the blood.

Question 7

What stimulates glucose uptake into tissue cells?

Answer 7

Insulin (uptake of glucose via transporters)

Question 8

Describe how glucose gets into adipose tissue & muscles.

Answer 8

The glucose transporter GLUT4 is sequestered in vesicles inside the cell. When insulin binds to an insulin receptor on the cell surface, it recruits GLUT4 to the cell surface. Now, excess glucose can come into the cell using GLUT4.

Question 9

Describe how glucose gets into liver cells.

Answer 9

In the liver, there is already GLUT2 transporters at the cell surface (passive diffusion transporter). High concentration of glucose in the blood causes it to enter the hepatocyte (liver cell). Insulin activates pathways by binding to the insulin receptors on the cell surface, that stimulate the production of glycogen in order to store glucose.

Question 10

What organ is responsible for keeping blood glucose concentration = 5.5 mM.

Answer 10

The liver.

Question 11

What is the role of the liver in the fed state?

Answer 11

Storing glucose as glycogen.

Question 12

What is the role of the liver in the fasting state?

Answer 12

1. Breaking down glycogen

2. Gluconeogenesis, when there is no glycogen left.

Question 13

What is the order of ATP expenditure during short duration, high intensity exercise?

(see L2.1 slide 21)

Answer 13

1. ATP stored in muscles
2. ATP formed from creatine phosphate and ADP.
   (P-creatine + ADP to creatine + ATP) [reversible}
3. Anaerobic glycolysis from glycogen stored in muscles.

Question 14

What does the ATP expenditure come from when you’ve reached prolonged duration exercise?

(see L2.1 slide 21)

Answer 14

ATP generated by aerobic pathway, and then finally aerobic lipolysis.

Question 15

What is the power-plant of ATP generation?

Answer 15

Oxidative phosphorylation

Question 16

What are the substrates needed to produce ATP in oxidative phosphorylation?

Answer 16

NADH, FADH2, O2

Question 17

What is the starting substrate of the citric acid cycle?What does the citric acid cycle produce?

Answer 17

1. Acetyl - CoA

2. NADH, FADH2, CO2, ATP per glucose

Question 18

What is the net production of glycolysis from one glucose?

Answer 18

2ATPs, 2NADH, 2 pyruvates

Question 19

Which process in the generation of ATP consumes oxygen?

Answer 19

Oxidative phosphorylation.

Question 20

What drives glycolysis forward?

Answer 20

Low [ATP]

Question 21

What slows down glycolysis?

Answer 21

Low [NAD+] ; High [ATP]

Question 22

What slows down the citric acid cycle?

Answer 22

High [NADH]

Question 23

What drives ox-phos forward?

Answer 23

Low [ATP]

Question 24

What slows down ox-phos?

Answer 24

High [ATP] ; Low [O2] ; Low [NADH/FADH2]

Question 25

What does glycolysis require in order to function?

Answer 25

NAD+

Question 26

In the presence of oxygen, what sequence of events leads to energy production?

Answer 26

1. Glycolysis
2. Citric acid cycle
3. Ox-phos

Question 27

What molecules must be invested in the investment phase of glycolysis?

Answer 27

2ATP per glucose

Question 28

How many molecules of NADH can be produced from one molecule of glucose? one molecule of glyceraldehyde-3-phosphate (GAP)?

Answer 28

2;1

Question 29

How many ATP’s are produced from each process of aerobic cellular respiration for one glucose?

Answer 29

Glycolysis: net = 2 ATP
Citric acid cycle = 2 ATP (1ATP per Acetyl CoA)
Ox-phos = 32 ATP

Question 30

What 3 enzymes are regulated due to the irreversibility of the glycolysis step (highly exergonic)? (in order)

Answer 30

1. Step 1: Hexokinase
2. Step 3: Phosphofructokinase (PFK1)
3. Step 10: Pyruvate kinase (PK)

Question 31

Go through the glycolysis pathway in order?

Answer 31

See L2.1 slide 27.

Question 32

What reaction and step does hexokinase catalyze in glycolysis?

Answer 32

Step 1: irreversible

Glucose + ATP —hexokinase, Mg2+—-> Glucose-6-Phosphate (G6P) + ADP

Question 33

What is the purpose of the first step of glycolysis?

Glucose -> G6P

Answer 33

1. It traps glucose inside the cell because phosphorylated compounds do not transport readily.
2. It keeps the concentration of glucose in the cytoplasm low to allow more glucose to be taken up. This allows glucose uptake without using ATP.

Question 34

What’s the substrate specificity of hexokinase?

Answer 34

Hexoses

Question 35

What is hexokinase’s tissue of prevalence?

Answer 35

All cell types

Question 36

Does hexokinase or glucokinase have a higher affinity for glucose?

Answer 36

Hexokinase (lower affinity constant = higher affinity)

Question 37

What regulates hexokinase?

Answer 37

Glucose-6-phosphate (allosteric)

Question 38

What rxn is catalyzed by glucokinase?

Answer 38

Glucose + ATP —> Glucose-6-Phosphate (G6P) + ADP

Question 39

What’s the substrate specificity of glucokinase?

Answer 39

Mainly glucose

Question 40

What is glucokinase’s tissue of prevalence?

Answer 40

Liver (and pancreas)

Question 41

What regulates glucokinase?

Answer 41

(nuclear) Glucokinase regulatory protein

Question 42

What is the metabolic consequence of having hexokinase and glucokinase catalyzing the same reaction in the liver?

Answer 42

Since hexokinase has a higher affinity for glucose, all cells will help themselves first with glucose. Then, the leftover circulating glucose will be converted to glycogen via glucokinase in the liver.

Also, hexokinase is useful when there is a small amount of glucose but it gets saturated with glucose very quickly when the glucose levels rise. Despite glucokinase’s low affinity, it has a high capacity to process the excess glucose.

Question 43

How does the glucokinase regulatory protein (GKRP) regulate glucokinase?

Answer 43

When glucose levels are low in the blood, GKRP sequesters GK in the nucleus.

When glucose levels are high, GKRP releases GK to the cytoplasm where it can produce G6P.