Module 04 - Gluconeogenesis and Glycogen Metabolism (Section 04)

Question 1

Which 3 main sources is blood glucose obtained from?

Answer 1

1. Diet
2. Gluconeogenesis
3. Glycogen Breakdown

Question 2

What is Glucose Metabolism?

Answer 2

the net production of glucose (gluconeogenesis) and breakdown of glucose (glycolysis)

Question 3

What is Gluconeogenesis?

Answer 3

an anabolic pathway that converts pyruvate (or lactate) to glucose

Question 4

Where does Gluconeogenesis occur?

Answer 4

partially in the mitochondria and partically in the cytoplasm of liver and kidney cells

Question 5

What are the 3 most important substrates for Gluconeogenesis?

Answer 5

1. Glycerol from the breakdown of lipids
2. Lactate released into the blood from red blood cells and exercising muscles
3. Amino acids released from breakdown of proteins and converted into a-keto acids during amino acid metabolism

Question 6

What is the Cori Cycle?

Answer 6

the metabolic pathway where lactate produced by anaerobic glycolysis in exercisng muscle cells is transported to the liver to be converted back to glucose

Question 7

What happens in step 1 of the cori cycle?

Answer 7

glucose from blood is taken up by intensely exercising skeletal muscle

Question 8

What happens in step 2 of the cori cycle?

Answer 8

anaerobic glycolysis converts glucose to lactate

Question 9

What happens in step 3 of the cori cycle?

Answer 9

lactate diffuses into the blood and is taken up by the liver

Question 10

What happens in step 4 of the cori cycle?

Answer 10

liver synthesizes glucose from lactate via gluconeogenesis

Question 11

What happens in step 5 of the cori cycle?

Answer 11

glucose is released back into the blood

Question 12

How many reactions is Gluconeogenesis comprised of?

Answer 12

11 reactions, including:
- 7 reversible reactions of glycolysis
- 4 reactions unique to gluconeogenesis

Question 13

What are the 4 unique reactions to gluconeogenesis?

Answer 13

1. conversion of pyruvate to oxaloacetate
2. formation of phosphoenolpyruvate
3. dephosphorylation of fructose 1,6-bisphosphate
4. dephosphorylation of glucose 6-phosphate

Question 14

What is pyruvate carboxylated by? Where does this take place?

Answer 14

pyruvate carboxylase in the mitochondria of liver and kidney cells

Question 15

What does pyruvate carboxylase use as a coenzyme?

Answer 15

biotin

Question 16

What occurs in step 1 of carboxylation of pyruvate?

Answer 16

hydrolysis of ATP to ADP powers the formation of an enzyme-biotin-CO2 intermediate

Question 17

What occurs in step 2 of carboxylation of pyruvate?

Answer 17

CO2 is transferred to pyruvate generating oxaloacetate and release the enzyme-biotin complex

Question 18

What is pyruvate carboxylase activated by?

Answer 18

acetyl-CoA

Question 19

What is pyruvate carboxylase inhibited by?

Answer 19

ADP

Question 20

What is oxaloacetate in the mitochondria reduced to to cross the mitochondrial membrane?

Answer 20

• maltate
• NADH is oxidized to NAD+

Question 21

What happens after maltate crosses into the cytosol?

Answer 21

it is oxidized back to oxaloacetate, with NADH regenerated from NAD+

Question 22

What happens to oxaloacetate once in the cytosol?

Answer 22

it is decarboxylated and phosphorylated by PEP-carboxykinase to form phosphoenolpyruvate (PEP)

Question 23

What happens to PEP in the cytosol?

Answer 23

it undergoes reversible reactions that are part of glycolysis until it is converted to fructose 1,6-bisphosphate

Question 24

What occurs during the dephosphorylation of fructose 1,6-bisphosphate?

Answer 24

phosphate is removed from fructose 1,6-bisphosphate by fructose 1,6-bisphosphatase

Question 25

What is fructose 1,6-bisphosphatase inhibited by?

Answer 25

high levels of AMP and fructose 2,6-bisphosphate

Question 26

What is fructose 1,6-bisphosphatase activated by?

Answer 26

citrate and ATP

Question 27

What is the product of PFK-2?

Answer 27

fructose 2,6-bisphosphate

Question 28

What is PFK-2? What is it regulated by?

Answer 28

a bifunctional protein that is regulated by the hormones insulin and glucagon

Question 29

What occurs during the dephosphorylation of glucose 6-phosphate?

Answer 29

- glucose 6-phosphate is transported to the lumen of the ER and dephosphorylated by glucose 6-phosphatase - once formed, glucose is shuttled back to the cytoplasm

Question 30

What does gluconeogenesis use/produce?

Answer 30

- uses 2 pyruvate, 4 ATP, 2 GTP, and 2 NADH - produces 1 glucose molecule

Question 31

How do glucagon levels stimulate gluconeogenesis?

Answer 31

1. decreases fructose 2,6-bisphosphate which activates fructose 1,6-bisphosphatase and inhibits PFK-1 2. leads to phosphorylation of pyruvate kinase, inactivating it which diverts PEP to glucose synthesis

Question 32

How does substrate abailability regulate gluconeogenesis?

Answer 32

in an energy poor state, proteins are broken down and amino acids provide substrates for gluconeogenesis

Question 33

How does allosteric activation of pyrucate carboxylase by acetyl-CoA regulate gluconeogenesis?

Answer 33

during starvation, breakdown of lipids results in increased acetyl-CoA

Question 34

Where does glycogen synthesis and degradation occur?

Answer 34

in the cytoplasm of cells

Question 35

Where is glycogen stored?

Answer 35

in the liver and skeletal muscle

Question 36

What does liver glycogen do?

Answer 36

maintains blood glucose levels, primarily during the initial stages of fasting

Question 37

What does muscle glycogen do?

Answer 37

functions as a fuel reserve for ATP synthesis during muscle contraction; muscle cells do not share their glycogen with the rest of the body

Question 38

Describe the structure of glycogen.

Answer 38

- branched-chain homopolysaccharide made up of a-D-glucosse held together by glycosidic bonds

Question 39

Describe the formation of glycosidic bonds of glycogen.

Answer 39

- primary bond is an a(1-4) linkage - after 8-10 glucose moecules, there is a branch formed by an a(1-6) linkage

Question 40

What is the source of all glucose molecules added to glycogen?

Answer 40

a-D-glucose attached to uridine diphosphate (UDP)

Question 41

Which two enzymes catalyze glycogen synthesis

Answer 41

- glycogen synthase: makes a(1-4) linkages - branching enzyme: makes a(1-6) linkages

Question 42

What occurs at the beginning of flycogen synthesis (glycogenesis)?

Answer 42

- UDP-glucose is synthesized from glucose 1-phosphate and UTP by UDP-glucose pyrophosphorylase

Question 43

What is UDP-glucose? How does it act in glycogensis?

Answer 43

- an activated, high energy form of glucose - acts as another source of energy, like ATP

Question 44

What occurs in the middle of glycogenesis?

Answer 44

glycogen synthase requires a primer fragment of glycogen; in the absence of a glycogen fragment, glycogenin can accept glucose molecules on the -OH of a Tyr side chain

Question 45

What occurs at the end of glucogenesis?

Answer 45

- chain elongation proceeds with the transfer of the glucose from UDP-glucose to the non-reducing end of the growing chain - chain branching is catalyzed by branching enzyme, which transfers a chain of 6-8 glucose by breaking a(1-4) bonds and forming an a(1-6) link

Question 46

What occurs during glycogen degradation (glycogenolysis)?

Answer 46

- produces glucose 1-phosphate from breaking a(1-4) glycosidic bonds and glucpse from breaking a(1-6) glycosidic bonds

Question 47

Which two enzymes do degradation of glycogen need?

Answer 47

- glycogen phosphorylase - debranching enzyme

Question 48

What does glycogen phosphorylase do?

Answer 48

cleaves a(1-4) linkages

Question 49

What does debranching enzyme do?

Answer 49

- glycosol (4,4) transferase activity removes the out 3 or 4 glucose molecules from the branch to the straight chain forming a new a(1-4) bond - a(1,6) glucosidase removes the remaining glucose

Question 50

What is synthesis of glycogen stimulated by?

Answer 50

high levels of glucose and ATP (well-fed state)

Question 51

What is breakdown of glycogen stimulated by?

Answer 51

low glucose and energy levels (fasted state)