Blake_BIochem_25_Glycolysis and Gluconeogenesis

Question 1

What are the irreversable steps in Glycolysis? (3)

• Substrate to product/Enzyme
  
  • side rxns

Answer 1

• Glucose ⇒ Glucose 6-phosphate/Hexokinase
  
  • ATP to ADP
• Fructose 6-Phosphate ⇒Fructose 1,6-biphosphate/ Phosphofructokinase
  
  • ​ATP to ADP
• Phosphoenolpyruvate ⇒Pyruvate/ Pyruvate kinase
  
  • ATP to ADP

Question 2

Stage one of Glycolysis (3)

• Substrate to product/Enzyme

Answer 2

• Glucose⇒Glucose 6-phosphate/ Hexokinase
• Glucose 6-phosphate ⇔ Fuctose 6-phosphate / Phosphoglucose Isomerase
• Fructose 6-phosphate⇒Fructose 1,6-biphosphate/ Phosphofructokinase

Question 3

Stage two Glycolysis (1)

• Substrate to Products/ Enzyme

Answer 3

• Fructose 1,6-biphosphate (splits)
  
  • ⇔ Glyceraldehyde 3-phosphate (GAP)/ Aldolase
  • ⇔Dihydroxyacetone phosphate/Aldolase
    
    • Dihydroxyacetone phosphate ⇔ Glyceraldehyde 3-phosphate (GAP)/triose phosphate isomerase

So there are 2 GAPs produced from 1 Glucose => phase 3 has twice the substrate

Question 4

Stage Three of Glycolysis

• Substrate to Products/ Enzyme

Answer 4

• Glyceraldehyde 3-phosphate (GAP) ⇔ 1,3-biphosphoglycerate/ GAPDH (​P_i, NAD⁺ ⇔ NADH)
• 1,3-Biphosphoglycerate ⇔ 3-Phosphoglycerate/ Phosphoglycerate kinase
• 3-Phosphoglycerate ⇔ 2- Phosphoglycerate/ Phosphoglycerate mutase
• 2- Phosphoglycerate ⇔ Phosphoenolpyruvate/ Enolase (​H₂O released)
• Phosphoenolpyruvate⇒ Pyruvate/ Pyruvate kinase (ATP to ADP)

Question 5

Gluconeogenesis vs Glycolysis

Enzyme Glycolysis/bypass enzyme gluconeogenesis

Answer 5

• Hexokinase (glucokinase) / Glucose 6-phosphatase
• Phosphofructokinase -1/ fructose 1,6-biphosphatase
• Pyruvate Kinase/ PEP carboxykinase
• **/ pyruvate carboxylase

Question 6

Which enzyme of Glycolosis is different in the Liver?

Answer 6

Hexokinase (other tissues); Glucokinase (in Liver)

Question 7

How many ATP are used/produced in phase 1 of Glycolysis

Answer 7

No ATP produced

2 ATP consumed

Question 8

What is the strategy of the initial steps of glycolysis? (2)

Answer 8

1. Trap the glucose in the cell
2. Form a compound that can be cleaved into 2, phosphorylated, three-carbon units

Question 9

GAPDH stands for:

Answer 9

Glyceraldehyde 3-Phosphate Dehydrogenase

Question 10

Where is GLUT1 used for glucose uptake?

Answer 10

Ubiquitously, but high in RBCs adn brain

Question 11

Where is GLUT2 used for Glucose Uptake?

Answer 11

Main transporter in the Liver

Question 12

Where is GLUT3 used for glucose uptake?

Answer 12

Neurons

Question 13

Where is GLUT4 used for glucose uptake?

Answer 13

Skeletal muscle, heart, adipose tissue (insulin dependent)

Question 14

Summarize Phase 1 Glycolysis:

Answer 14

trapping and preparation

Question 15

Summarize Phase 2 Glycolysis:

Answer 15

Cleavage and isomerization

Question 16

Sumarize Phase 3 Glycolysis:

Answer 16

3 steps: producing x2 Pyruvate

• GAPDH
• Phosphoglycerate kinase/mutase
• Enolase/pyruvate kinase

Question 17

What is the rate-limitting step in Glycolysis?

Answer 17

Phosphoenolpyruvate to Pyruvate

Question 18

What are the different fates of pyruvate depending on the presence or absence of O₂?

Answer 18

with O₂: Aerobic respiration; Pyruvate to TCA cycle

without O₂: Anaerobic respiration; Pyruvate reduced to Lactate

Question 19

In what tissues is glycolysis regulated:

Answer 19

• In muscle - to meet need for ATP during Exercise
• In Liver - in response to biochemical diversity and need

Question 20

How is Glycolysis regulated in muscle tissues during rest?

What about Glycogen?

Answer 20

• Hexokinase is inhibited by Glucose 6-phosphate
• Phosphofructokinase (PFK) and Pyruvate Kinase are inhibited by ATP
• Glucose 6-phosphate is converted to glycogen

Question 21

How is glycolysis regulated in muscle tissues during exercise?

What about Glycogen?

Answer 21

• PFK is stimulated by low energy AMP
• Fructose 1,6 biphosphate feedforward stimulation of Pyruvate kinase
• Glycogen is converted to Glucose 6-phosphate

Question 22

How is glycolysis regulated in the liver?

Answer 22

• Phosphofuctokinase (PFK)
  
  • Activated by Fructose-2,6-BP
  • Inhibited by citrate
• Glucokinase is NOT inhibted by glucose 6-phosphate (like hexokinase in other tissues) therefore, glucose is permanently trapped
• Pyruvate kinase is regulated by allosteric effectors and covalent modification

Question 23

How does [Insulin] and [Glucagon] affect Phosphofructokinase (PFK) in the liver?

Answer 23

• High Insulin/low glucagon: stimulates protein phosphatases which stimulates PFK-2 to produce Fructose 2,6BP which stimulates PFK-1
• Low insulin/high glucagon increases [cAMP] which stimulates Protein kinase A which stimulates PFK-2 to produce Fructose 6-P

Question 24

How does [Insulin] and [Glucagon] affect Pyruvate Kinase (PK) in the liver?

Answer 24

• high insulin/low glucagon: stimulates protein phosphatases which stimulates PK
• low insulin/high glucagon: increases [cAMP] which stimulates protein kinase A which inhibits PK

Question 25

how is Glucokinase regulated by blood glucose?

Answer 25

low blood glucose = inhibition - don't want to trap glucose

Question 26

What is the fate of pyruvate under Aerobic Fasting conditions?

Answer 26

Gluconeogenesis

Question 27

daily glucose requirement for the brain? for the whole body? glucose in body fluids? Glucose available from glycogen?

Answer 27

120g 160g 20g 190g

Question 28

Substrates in order for Gluconeogenesis:

Answer 28

* Pyruvate * **Oxaloacetate** * phosphoenolpyruvate * 2-phosphoglycerate * 3-phosphoglycerate * 1,3-biphosphoglycerate * GAP/Dihydroxyacetone phosphate * Fructose 1,6,-biphosphate * Fructose 6-phosphate * Glucose 6-phosphate * Glucose