Gluconeogenesis

Question 1

Gluconeogenesis

Answer 1

• occurs in the cytoplasm and mitochondria, predominantly in the liver
• anabolic pathway – requires ATP
• occurs during fasting when there is a decrease in glycogen reserves
• synthesis of glucose from noncarbohydrate precursors including pyruvate, lactate, glycerol and amino acids
• inhibited by insulin
• promoted by glucagon

Question 2

What are the substrates for gluconeogenesis?

Answer 2

• glycerol 3-phosphate (from stored fats, triacylglycerols in adipose tissue)
• lactate (from anaerobic glycolysis)
• glucogenic amino acids (from muscle proteins)

Question 3

What lowers blood sugar levels?

Answer 3

insulin

Question 4

What raises blood sugar levels?

Answer 4

stimulation of gluconeogeneis and glycogenolysis by: glucagon, epinephrine, cortisol, growth hormone

Question 5

Glucogenic Amino Acids

Answer 5

• amino acids that can be converted into intermediates that feed into gluconeogenesis
• includes all amino acids except for leucine and lysine
• catabolism of one of these AAs produce either pyruvate or one of the intermediates in the Krebs Cycle

Question 6

Ketogenic Amino Acids

Answer 6

• amino acids that can be converted into ketone bodies that can be used as an alternative fuel especially during periods of starvation
• includes: leucine, isoleucine, tryptophan, lysine, tyrosine, phenylalanine
• catabolism of these AAs produces acetyl CoA or acetoacetyl CoA

Question 7

List the enzymes in the order they occur during Gluconeogenesis (11)

Answer 7

1. Pyruvate Carboxylase
2. Phosphoenolpyruvate Carboxykinase
3. Enolase
4. Phosphoglycerate Mutase
5. Phosphoglycerate Kinase
6. Glyceraldehyde 3-Phosphate Dehydrogenase
   (7. Triose Phosphate Isomerase)
7. Fructose Bisphosphate Aldose
8. Fructose 1,6-Bisphosphatase-1 (FBPase-1)
9. Phosphohexose Isomerase
10. Glucose 6-Phosphatase

Question 8

Pyruvate Carboxylase

Answer 8

• mitochondrial enzyme
• requires 1 ATP
• converts pyruvate into oxaloacetate (adds another carbon)
• activated by acetyl CoA (from beta-oxidation) and ATP
• inhibited by ADP/AMP

Question 9

Oxaloacetate

Answer 9

• CAC intermediate
• can’t leave mitochondria so is reduced to malate that leaves mitochondria via malate-aspartate shuttle then in cytoplasm malate is oxidized back to oxaloacetate

Question 10

Phosphoenolpyruvate Carboxykinase (PEPCK)

Answer 10

• located in cytoplasm
• converts oxaloacetate to PEP in a reaction that requires GTP
• phosphorylates oxaloacetate to form PEP
• activated by glucagon and cortisol

Question 11

___ and ___ enzymes are used to avoid the action of pyruvate kinase by converting pyruvate back into PEP

Answer 11

pyruvate carboxylase and PEPCK

Question 12

Fructose 1,6-Bisphosphatase (FBPase-1)

Answer 12

• located in cytoplasm
• key control point
• rate limiting step
• removes a phosphate from fructose 1,6-bisphosphate to produce Fructose 6-Phosphate
• activated by ATP
• inhibited by AMP and Fructose 2,6-Bisphosphate

Question 13

How does Glucagon effect Fructose 2,6-Bisphosphate?

Answer 13

it lowers levels of Fructose 2,6-BP which stimulates gluconeogenesis

Question 14

How does Insulin effect Fructose 2,6-Bisphosphate?

Answer 14

it increases levels of Fructose 2,6-BP which inhibits gluconeogenesis

Question 15

Glucose 6-Phosphatase

Answer 15

• found in lumen of ER in liver cells
• used to avoid glucokinase and hexokinase
• converts glucose 6-phosphate into glucose (glucose can now leave cell via GLUT transporters)
• absence of this in muscles means that muscle glycogen can’t serve as a source of blood glucose
• enzyme is also used during breakdown of glycogen

Question 16

What is the source of Acetyl CoA used in gluconeogenesis?

Answer 16

Beta-Oxidation of Fatty Acids

-this process also provides ATP for gluconeogenesis to occur

Question 17

Phosphatase vs. Kinase

Answer 17

• Phosphatase: removes phosphate groups from a molecule

- Kinase: phosphorylation of a molecule, usually using phosphate groups from molecules like ATP

Question 18

Hypoglycemic

Answer 18

• individuals that have low levels of glucose
• occurs in individuals that are missing the glucose 6-phosphatase enzyme because they are unable to from glucose during gluconeogenesis but also can’t breakdown glycogen into glucose

Question 19

Net reaction for Gluconeogenesis

Answer 19

2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H+ + 6 H2O ->

glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi