Kaplan Ch.9 - Carbohydrate Metabolism 1

Question 1

What is GLUT 2?

What is it’s function?

Answer 1

A low affinity (high Km) transporter in hepatic and pancreatic cells.

In liver: it captures excess glucose in the blood from the hepatic portal vein for storage, most effective when [glucose] is high

In pancreas: serves as glucose sensor for insulin release

Question 2

GLUT 4:

1) what tissues is this transporter found in?
2) what is this protein?
3) what hormone does it respond to and how?
4) what is the Km of this transporter for glucose and what does that mean regarding meals?

Answer 2

1) muscle and adipose tissue
2) a transporter of glucose
3) respond to insulin, which stimulates movement of additional GLUT 4 transporters to the membrane via vesicles that have GLUT 4 on their membranes and then fuse with the plasma membrane to introduce more membrane and more transporters
4) Km is close to [normal blood glucose], which is 5.6mM. Thus, when eating a meal, [glucose] is much higher and all GLUT 4 transporters are saturated providing a constant rate of transport into adipose and muscle tissue.

Question 3

How is glucose uses in fat cells?

Answer 3

Glucose is used to form dihydroxyacetone phosphate (DHAP) which is converted to glycerol phosphate to store incoming fatty acids as triacylglycerols

Question 4

Where does glycolysis occur?

Answer 4

In the cytoplasm of all cells

Question 5

Glycolysis converts ___ into ___, releasing a modest amount of energy via 2 _____ and 1 _____.

Answer 5

Glucose
Two pyruvate
Substrate level phosphorylations
Oxidation reaction

Question 6

Hexokinase:

1) what does it do?
2) what cells is it located in?
3) how is this enzyme inhibited?

Answer 6

1) phosphorylates glucose to glucose 6P, which traps the glucose inside the cell so it can’t diffuse out via the GLUT transporters
2) most cells of most tissues
3) allosteric negative feedback where it is inhibited by its own product (glucose 6P)

Question 7

Glucokinase:

1) what does it do?
2) Where is this enzyme located?
3) activated by?

Answer 7

1) phosphorylate glucose to glucose 6P trapping it inside cell
2) liver and pancreas
3) Insulin

Question 8

Phosphofructokinase I (PFK I)

1) what does this enzyme do?
2) why is this step important in glycolysis?
3) what inhibited PFK-I and why?
4) what activates PFK-1 and why?

Answer 8

1) phosphorylates fructose 6P to fructose 1,6 bis P
2) it is the rate limiting step
3) High [ATP] and [citrate] inhibit PFK-1 because these are both indicators that the cell has sufficient energy so there is no need to make more
4) high [AMP] because this indicates there is not enough energy in the cell and more needs to be made

Question 9

In liver cells, what effect does insulin have on PFK-1? What effect does glucagon have?

Answer 9

Insulin stimulates, Glucagon inhibits both via PFK-2

Question 10

Explain the function of PFK-2 in liver cells.

Answer 10

Insulin stimulates PFK-2 to convert a small amount of fructose 6P into fructose 2,6 BisP which activates PFK-1. Glucagon does the opposite (inhibits). This mechanism allows liver cells to override the inhibition caused by large amounts of ATP so that glycolysis can continue to allow for glycogen and fatty acid storage.

Question 11

What is the function of glyceraldehyde 3 phosphate dehydrogenase?

Answer 11

It catalyzes an ox/redox rxn and addition of an inorganic phosphate group to glyceraldehyde 3 phosphate to form 1,3 bisphosphoglycerate and NADH (can enter ETC if oxygen is present)

Question 12

What is the function of 3-phosphoglycerate kinase?

Answer 12

Transfers a high energy phosphate from 1,3 BPG to ADP, generating 1 molecule of ATP via substrate level phosphorylation and 3 - phosphoglycerate.

Question 13

What is the function of pyruvate kinase?

Answer 13

Transfers a high energy phosphate from phosphoenolpyruvate (PEP) to ADP to form 1 molecule of ATP and 1 molecule of pyruvate.

Question 14

Fermentation:

1) what is the general process of fermentation?
2) how does this process differ in yeast?

Answer 14

1) pyruvate is reduced to lactate and NADH is oxidized to NAD+, which then is able to participate in glycolysis because NAD+ is the coenzyme for glyceraldehyde 3 phosphate dehydrogenase (convert G3P to 1,3 BPG).
2) byproducts are CO2, ethanol and heat

Question 15

What are the 3 possible fates of pyruvate?

Answer 15

1) be converted to lactate by lactate dehydrogenase and undergo fermentation
2) be converted to acetyl co A by PDH and enter the CAC or fatty acid synthesis
3) be converted to oxaloacetate by pyruvate carboxylase and enter gluconeogenesis

Question 16

What does the PDH complex require to function?

Answer 16

Numerous cofactors and coenzymes, such as thiamine, pyrophosphate, lipoic acid, CoA, NAD+ and FAD

Question 17

What inhibits PDH?

Answer 17

Build up of acetyl CoA

Question 18

Where does glycogen synthesis and storage occur?

Answer 18

In the liver and skeletal muscle

Question 19

In the cell, where is glycogen stored? How is it stored?

Answer 19

Stored in the cytoplasm in the form of granules. Granules have a protein core with glucose chains radiating outward to form a sphere

Question 20

What is glycogen stored in the liver used for? In skeletal muscle?

Answer 20

Liver: prevent low blood sugar between meals
Muscle: energy reserve for muscle contraction

Question 21

Explain the process of glycogenesis.

Answer 21

Begins with core protein called glycogenin. Glucose 6 phosphate is converted to glucose 1 phosphate, which then combines with a molecule of UDP and becomes activated as UDP-Glucose. This releases a pyrophosphate. Glycogen synthase can then add this activated glucose to the growing glucose chain radiating from the protein core.

Question 22

Glycogen synthase:

1) why is this step important?
2) what kind of glycosidic linkages does it form?
3) what is it stimulated by?
4) how is it inhibited?

Answer 22

1) it is the rate limiting step
2) alpha 1,4 (linear)
3) glucose 6P and insulin
4) epinephrine, increased [AMP], and glucagon all initiate a cascade that results in phosphorylation of glycogen synthase thus inhibiting it’s activity

Question 23

Branching enzyme: what does this enzyme do?

Answer 23

in glycogenesis, it makes alpha 1,6 linkages which produces a branch

Question 24

Describe glycogenolysis.

Answer 24

Glycogen is broken down into individual oligosaccharides via glycogen phosphorylase.

Question 25

Glycogen phosphorylase:

1) what does it break? How?
2) what does it release?
3) what can it not break?
4) activated by ___ in liver
5) activated by ___ in skeletal muscle
6) inhibited by?

Answer 25

1) alpha 1,4 linkages using an inorganic phosphate group instead of water
2) releases glucose 1P which is converted to glucose 6P by glucose 6 phosphatase
3) cannot break alpha 1,6 linkages
4) glucagon
5) AMP and epinephrine
6) ATP

Question 26

Debranching enzyme: what is the function of this enzyme?

Answer 26

Deconstructs the branches of glycogen. Does this by breaking an alpha 1,4 bond adjacent to branch point, moving that chain to the exposed end of the other chain forming a new alpha 1,4 bond, cleaning the alpha 1,6 bond of the remaining glucose molecule that was from the branch.

Question 27

Gluconeogenesis:

1) what is it?
2) what activates this process? Inhibits it?
3) what are the important substrates?

Answer 27

1) formation of glucose from sources other than food or glycogen stores
2) activated by glucagon and epinephrine, inhibited by insulin
3) glycerol 3 P (from fatty acids), lactate (from anaerobic glycolysis), amino acids

Question 28

Glucogenic amino acids

Ketogenic amino acids

Answer 28

AAs that can be converted to intermediates that enter gluconeogenesis

AAs that are made into ketone bodies which can also be used for fuel

Question 29

Give a brief explanation of the pathway of gluconeogenesis.

Answer 29

In mitochondria of the liver, beta oxidation of fatty acids produces acetyl CoA which activates pyruvate carboxylate which turns pyruvate into oxaloacetic acid. OAA is converted to Malate, then leaves the mitochondria via the malate aspartate shuttle to the cytoplasm where it is converted back to OAA. Phosphoenolpyruvate carboxykinase (PEPCK) then converts OAA to PEP. PEP then undergoes several reversible steps of glycolysis in the reverse direction of glycolysis to form fructose 1,6 bisP. Fructose 1,6 bisP is converted to fructose 6P via fructose 1,6 bisphosphatase (removes Pi). This is the rate limiting step for gluconeogenesis as it was for glycolysis. Fructose 6 P is converted to glucose 6P by isomerase and then glucose 6P is converted to glucose by glucose 6 phosphatase. The last step occurs in the ER of the liver cells and the free glucose is transported out of the ER to the cytoplasm where it can diffuse out of the liver cell and into the blood stream to maintain blood sugar.

Question 30

What is the importance of the pentose phosphate pathway?

Answer 30

(1) It makes ribose 5 phosphate, and when combined with a nitrogenous base this makes nucleic acids
(2) it makes NADPH

Question 31

What is NADPH and why is it important in cells?

Answer 31

It is a powerful reducing agent (helps other molecules become reduced and is itself oxidized).

It is important in biosynthesis and creation of glutathionine which protects against reactive oxygen species (free radicals)