Gluconeogenesis- Lecture 66

Question 1

What conditions trigger gluconeogenesis?

Answer 1

low glucose/carb diet
fasting/starvation
diabetes

Question 2

Where is glucose synthesized?

Answer 2

mostly by the liver and small amounts by the kidney

Question 3

What are the primary substrates for synthesizing glucose?

Answer 3

lactate, pyruvate, gluconeogenic amino acids, and glycerol from breakdown of triglycerides (less of the time)

Question 4

What is the net reaction for gluconeogenesis?

Answer 4

2 Pyr + 2 GTP + 4 ATP + 2 NADH –> Glucose + 2GDP + 4 ADP + 2 NAD+ + 6 Pi

Question 5

What enzymes differ between glycolysis and gluconeogenesis?

Answer 5

Original: pyr kinase/pyruvate dehydrogenase (step 10), PF-1K (step 3), GK/HK step (step 1)
New: PEP carboxykinase/pyruvate carbozylase (step 10), F1,6bisPhase (step 3), G6Pase (step 1)

Question 6

Describe the pathway of gluconeogenesis from lactate.

Answer 6

1. Lactate –> pyruvate
   (via lactate dehydrogenase)
2. pyruvate + ATP + CO2 –> OAA + ADP + Pi
   (via pyruvate carboxylase only in mitochondria)
3. OAA + GTP –> PEP + CO2 + GDP
   (via PEPCK)
   4-11. 2 PEP –> F1,6bisP reversal of glycolysis
   (via enolase, phosphoglyceromutase, phosphoglycerokinase, G3PDH, and aldolase)

Question 7

What regulates gluconeogenic enzymes PEPCK and pyruvate carboxylase?

Answer 7

Glucagon/epi increase levels

insulin lowers levels

Question 8

What regulates gluconeogenic enzyme pyruvate kinase?

Answer 8

Acetyl CoA inhibits

Question 9

What regulates pyruvate carboxylase?

Answer 9

Acetyl CoA stimulates

Question 10

____ high energy bonds are required to synthesize glucose via gluconeogenesis because of the need to _______.

Answer 10

6

overcome irreversible steps of glycolysis

Question 11

Which reactions would result in futile cycles if unregulated?

Answer 11

the three irreversible reactions of glycolysis running at the same time as their gluconeogenesis counterparts

Question 12

What is a futile cycle?

Answer 12

when energy is lost because two reactions are occurring simultaneously in opposite directions

Question 13

What regulates the PK and PC/PEPCK futile cycle?

Answer 13

glucagon increases PEPCK and PC but inhibits PK
insulin increases PK activity but decreases PEPCK
high energy signals stimulate PC but inhibit PK

Question 14

What regulates the PFK and F1,6bisPhase futile cycle?

Answer 14

glucagon increases F1,6bisPhase but inhibits PRK (via F2,6bisP cycle)
insulin decreases F1,6bisPhase but increases PRK (via F2,6bisP cycle)
ATP and citrate stimulate F1,6bisPase but inhibit PFK
low energy signals (AMP, Pi, NH4) inhibit F1,6bisPhase but stimulate PFK

Question 15

What regulates the HK/GK and G6Pase futile cycle?

Answer 15

glucagon increases G6Pase but inhibits GK

insulin inhibits G6Pase but increases GK