Unit 11

Question 1

What is meant by the term gluconeogenesis?

Answer 1

• The biosynthesis of a carbohydrate from simpler, noncarbohydrate precursors such as oxaloacetate or pyruvate
  *converts pyruvate and related 3-4 carbon compounds into glucose

Question 2

Why is gluconeogenesis important in animals?

Answer 2

This process is important because some tissues depend almost completely on glucose for their metabolic energy and unfortunately, the supply of glucose from these stores is not always sufficient (between meals and fasting)

Question 3

In what tissues does it mainly occur?

Answer 3

Usually occurs in the liver

Question 4

Name three non-carbohydrate precursors of glucose

Answer 4

Pyruvate
Glucogenic amino acids
Triacyl-glycerols/glycerols

Question 5

What does lactate turn into?

Answer 5

Pyruvate and then into the TCA cycle

Question 6

What do glucogenic amino acids turn into?

Answer 6

Nothing, they just enter the TCA cycle

Question 7

What do triacyl-glycerols turn into?

Answer 7

Glycerol and then they enter the TCA cycle

Question 8

Why does gluconeogenesis require a pathway different than the reversal of glycolysis?

Answer 8

• Because there are three reaction son glycolysis that are essentially irreversible and cannot be used in gluconeogenesis: the conversion of glucose to glucose-6-phosphate by hexokinase, the phosphorylation of fructose 6-phosphate into fructose- 1,6- phosphate by phosphofructokinase-1, and the conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase

Question 9

Which steps of glycolysis are irreversible?

Answer 9

the conversion of glucose to glucose-6-phosphate by hexokinase, the phosphorylation of fructose 6-phosphate into fructose- 1,6- phosphate by phosphofructokinase-1, and the conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase

Question 10

Bypass 1

Answer 10

Conversion of pyruvate to phosphoenolpyruvate (PEP)

Question 11

Using structures, write balanced equations for the reactions involved

Answer 11

Pyruvate + ATP + GTP + HCO3- –> PEP + ADP + GDP + Pi + CO2

Question 12

Name the cofactor used by pyruvate carboxylase and describe its function

Answer 12

Biotin. Biotin transfers CO2 from Site 1 to Site two so it can meet with pyruvate to form oxaloacetate

Question 13

What is the role of ATP in the conversion of pyruvate?

Answer 13

To turn HCO3- into CO2

Question 14

Draw the creation of oxaloacetate using pyruvate carboxylase

Question 15

In this series of reactions, pyruvate is first carboxylated to oxaloacetate and then decarboxylated to phosphoenolpyruvate. Why is this series of steps important?

Answer 15

This carboxylation-decarboxylation sequence represents a way of activating pyruvate, in that the decarboxylation of oxaloacetate facilitates PEP formation

Question 16

Discuss two alternate pathways from pyruvate to phosphoenolpyruvate. What is the purpose of the variation in the pathway from pyruvate?

Answer 16

NADH and H+ are required to be made in the cytosol. Since starting from lactate will generate NADH in the cytosol when it turns into pyruvate, it can generate PEP in the mitochondria. However, if you start with pyruvate, you must take extra steps to convert oxaloacetate to malate and back to oxaloacetate just to generate NADH in the cytosol

Question 17

Write a balanced equation for the reaction catalyzed by fructose 1,6-bisphosphatase (FBPase-1). Name the type of reaction

Answer 17

Fructose 1,6-phosphate + H20 –> Fructose 6-phosphate +Pi

HYDROLYSIS REACTION

Question 18

Write a balanced equation for the reaction catalyzed by glucose 6 phosphate. Name the type of reaction

Answer 18

Glucose 6-phosphate + H20 –> glucose + Pi

HYDROLYSIS REACTIOn

Question 19

Summarize the bioenergetics of glycolysis and gluconeogenesis

Answer 19

glucose –> 2 pyruvate +2 ATP
2 pyruvate –> glucose -6 ATP

Question 20

Account for the 6 ATPs required for gluconeogenesis. Remember that we are dealing with the conversion of two moles of pyruvate and that energetically, ATP and GTP are equibalent

Answer 20

• 2 ATPs are used by pyruvate carboxylase (to go from pyruvate to oxaloacetate)
• 2 GTPs are used by PEP carboxykinase to go from Oxaloacetate to PEP
• 2 ATPs are used by 3-Phosphoglycerate to turn into 1,3-Bisphosphoglycerate

Question 21

Which other step in gluconeogenesis can be described as an energy input?

Answer 21

1,3-Bisphosphoglycerate –> (2) Glyceraldehyde 3 phosphate

Question 22

Why would it be wasteful for a cell to simultaneously carry out both glycolysis and gluconeogenesis? How is this prevented?

Answer 22

It would be wasteful because glycolysis only generates 2 ATPs while gluconeogenesis uses up 6 ATPs. If both cycles were to go at the same time, you would lose 4 ATPs which is not effective. This process is prevented through reciprocal regulation

Question 23

Discuss the reciprocal regulation of PFK-1 and FBPase-1 by AMP (DRAW THIS WHOLE DIAGRAM)

Answer 23

When AMP levels are high, it drives the activation of PFK-1 and inhibits the activation of FBPase-1. This encourages glycolysis and limits FBPase-1 so that gluconeogenesis isn’t occuring

Question 24

Discuss the reciprocal regulation of PFK-1 and FBPase-1 by fructose 2,6-bisphosphate (DRAW SIMRITA’S DIAGRAM)

Question 25

Discuss how/when fructose 2,6-bisphosphate accumulates in the cell (DRAW BOTH DIAGRAMS)

Answer 25

Fructose 2,6-bisphosphate is regulated by the enzymes insulin and glucagon which control PFK-2 and FBPase 2. Insulin activates glycolysis and inhibits gluconeogenesis. Glucagon activates gluconeogenesis and inhibits glycolysis

Insulin REMOVES a phosphate group from the PFK-2 and FBPase-2 to activate the PFK-2 and stimulate glycolysis. Glucagon adds a phosphate group to the complex to activate FBPase and inhibit PFK-2

Question 26

Discuss the reciprocal regulation of pyruvate carboxylase and the enzyme that prepares pyruvate for entry into the citric acid cycle, pyruvate dehydrogenase (DRAW DIAGRAM)

Answer 26

When pyruvate turns into acetyl-CoA, an enzyme called pyruvate dehydrogenase facilitates that pathway. When pyruvate is converted into oxaloacetate, that is done by pyruvate carboxylase and activates gluconeogenesis. Production of acetyl-CoA is the commitment to entering the citric acid cycle. When there is too much acetyl-CoA, it will inhibit the production of pyruvate dehydrogenase so no more of it can be made. It will also upregulate pyruvate carboxylase to promote gluconeogenesis

Question 27

What is teh name of the enzyme complex that forms acetyl-CoA from pyruvase?

Answer 27

PDH complex

Question 28

Write the net reaction catalyzed by the pyruvate dehydrogenase complex (DRAW IT OUT)

Answer 28

Pyruvate + CoASH + NAD+ + TPP + lipoate + FAD –> CO2 + Acetyl-CoA

Question 29

How many coenzymes are involved in the conversion of pyruvate to acetyl-CoA?

Answer 29

5:
- TPP
- lipoate
- FAD
- NAD+
- CoA-SH

Question 30

How many enzymes are involved in the conversion of pyruvate to acetyl-CoA?

Answer 30

3 enzymes:
E1, E2, E3

Question 31

Discuss “substrate channeling”. What is the advantage of having these enzymes organized into a complex

Answer 31

Movement of the chemical intermediates in a series of enzyme-catalyzed reactions from the active-site of one enzyme to that of the next enzyme in the pathway. This is advantageous because the rate increases and it prevents the loss of intermediates

Question 32

What is the function of FAD and NAD+ in the reaction pathway. Does it seem odd that FADH2 is strong enough to reduce NAD+ to NADH? Explain how this is possible

Question 33

DRAW STEP 1 OF CITRIC ACID CYCLE

Answer 33

Claisen Condensation

Enzyme that catalyzes this reaction: Citrate synthase

Acetyl-CoA + Oxaloactate –> Citroyl CoA –> Citrate

Question 34

DRAW STEP 2 OF CITRIC ACID CYCLE

Answer 34

Dehydration, Rehydration

Enzyme that catalyzes this reaction: Acoritase

Citrate (-H20) –> Cos-Acoritate –> (+H20) isocitrate
`
*OH is added to a different carbon

Question 35

DRAW STEP 3 OF CITRIC ACID CYCLE

Answer 35

Dehydrogenation

Enzyme that catalyzes this reaction:
Isocitrate dehydrogenase

Isocitrate + NAD+ –> NADH + CO2(-) + alpha-ketoglutarate

Question 36

DRAW STEP 4 OF CITRIC ACID CYCLE

Answer 36

Oxidative decarboxylation

Enzyme that catalyzes this reaction:
alpha-ketoglutarate dehydrogenase complex

Alpha-ketoglutarate + NAD+ + CoA-SH –> succinyl CoA

Question 37

How can one explain the ability of an enzyme to distinguish between the two ends of a compound like citrate?

Answer 37

Aconitate has 3 binding points that isocitrate can bind to. If the molecule is still symmetrical, it will not be able to bind to the site properly. So it will only be able to properly bind the other way

Question 38

List the four oxidation reactions of the citric acid cycle and tell which coenzymes picks up electrons and H atoms released in each of these rxns

Answer 38

• Isocitrate –> alpha-ketoglutarate (NAD)
• Alpha-ketoglutarate –> succinyl CoA (NAD)
• Succinate –> Fumarate (FAD)
• Malate –> Oxaloacetate (NAD)

Question 39

What eventually happens to these electrons and H atoms?

Answer 39

They enter the electron transport chain

Question 40

How many molecules of reduced coenzymes are produced from one molecule of glucose?

Answer 40

10 NADH
2 FADH2
4 ATP

Question 41

In the cell, the citric acid cycle is an important catabolic pathway. Name the three classes of molecules that undergo their final oxidation in the citric acid cycle

Answer 41

Fats, carbohydrates, and proteins

Question 42

List the anabolic functions of the citric acid cycle

Answer 42

Citrate –> fatty acids, sterols
Alpha-ketoglutarate –> purines, amino acids
Succinyl CoA –> heme
Oxaloacetate –> pyrimidines, amino acids

PEP –> Glucose and amino acids

Question 43

Define anaplerotic reaction and explain the metabolic importance of the above reaction

Answer 43

• An enzyme-catalyzed reaction that can replenish the supply of intermediates in the citric acid cycle
• This is important bc if all of the intermediates were used up, we would be unable to make oxaloacetate - the goal