Glyconeogenesis

Question 1

What are the requirements for gluconeogenesis?

Answer 1

~ availability of precursors (pyruvate, a.a.s etc.)
~ spare energy
~ enzymes present

Question 2

Gluconeogenesis

Answer 2

the generation of glucose from non-carbohydrate carbon substrates

Question 3

Which glycolysis steps are reversed in gluconeogenesis?

Answer 3

steps 4-9 but energy input is required
step 7 –> ATP
step 6 –> NADH

Question 4

Reversal of glycolysis step 10

Answer 4

~ part 1 and 2 occur in mitochondria

1. pyruvate + Ac-CoA + ATP –> oxaloacetate
2. oxaloacetate + NADH + H+ –> malate
3. malate + NAD+ –> oxaloacetate
4. oxaloacetate + GTP –> PEP

Question 5

Reversal of glycolysis step 10 - enzyme used in part 1

Answer 5

pyruvate + Ac-CoA + ATP –> oxaloacetate

pyruvate carboxylase

Question 6

Reversal of glycolysis step 10 - enzyme used in part 2

Answer 6

oxaloacetate + NADH + H+ –> malate

mitochondrial malate dehydrogenase

Question 7

Reversal of glycolysis step 10 - enzyme used in part 3

Answer 7

malate + NAD+ –> oxaloacetate

cytoplasmic malate dehydrogenase

Question 8

Reversal of glycolysis step 10 - enzyme used in part 4

Answer 8

oxaloacetate + GTP –> PEP

phosphoenolpyruvate carboxykinase

Question 9

Reversal of glycolysis step 3 and 1

Answer 9

1. fructose-1,6-bisphosphate –> fructose-6-phosphate
2. fructose-6-phosphate glucose-6-phosphate
3. glucose-6-phosphate –> glucose or glycogen

Question 10

Enzymes used in the reversal of glycolysis steps 3-1

Answer 10

1. fructose-1,6-bisphosphatase
2. glucose-6-phosphate isomerase
3. glucose-6-phosphatase (liver and kidney only)

Question 11

How many high-energy bonds are broken in gluconeogenesis compared to glycolysis?

Answer 11

glycolysis =4

gluconeogenesis = 6 = energetically unfavourable

Question 12

Gluconeogenesis/glycolysis regulation (step 3)

Answer 12

~ reciprocally regulated (only one activate at a time)
~ AMP + F-2,6-BP increase glycolysis activity and decrease glucneogenesis activity
~ Citrate decreases glycolysis activity and increases glucneogenesis activity
glycolysis = PFK
gluconeogenesis = F-1,6-BPhosphatase

Question 13

Gluconeogenesis/glycolysis regulation (step 10)

Answer 13

~ ATP decreases glycolysis activity and increases glucneogenesis activity
glycolysis = Pyruvate kinase
gluconeogenesis = Pyruvate carboxylase

Question 14

Fructose-2,6-bisphosphatase + insulin/glucagon

Answer 14

~ hormones regulate its phosphorylation
~ insulin activates phosphatase = removes phosphate
~ glucagon activate cAMP-dependent kinase which adds a phosphate

Question 15

Fructose-2,6-bisphosphatase or phosphofructokinase?

Answer 15

~ bifunctional enzyme controlled by phosphorylation
~ when phosphorylated = Fructose-2,6-bisphosphatase
- stimulates gluconeogenesis + inhibits glycolysis
~ reverse when not phosphorylated