L9, 10, 11: Glucose Metabolism

Question 1

Sources of glucose

Answer 1

1. Dietary carbohydrates
2. Amino acids (gluconeogenesis)
3. Glycerol (gluconeogenesis)
4. Glycogen (glycogenolysis)

Question 2

***Pathways involved in glucose metabolism

Answer 2

1. Glycolysis / gluconeogenesis —> pyruvate, 2 net ATP
2. TCA cycle (Krebs/citric acid) —> 3 NADH, 1 FAD2H
3. Oxidative phosphorylation —> ATP
4. Pentose phosphate pathway —> NADPH, ATP, Pentose phosphate for nucleic acid synthesis
5. Glycogenesis —> glycogen (glycoconjugates) from UDP glucose
6. Produce TAG (glycerol + FA from TCA cycle) + Amino acids

Question 3

Glucose metabolism pathway

Answer 3

Glucose —> G-6-P —> F-6-P —> F-1,6-BP —> phosphoenolpyruvate —> pyruvate —> Acetyl-CoA —> (OAA —> Citrate)

Question 4

How glycolysis produce ATP

Answer 4

• 1,3 biphosphoglycerate —> 3 phosphoglycerate (Phosphoglycerate Kinase)
• phosphoenolpyruvate —> pyruvate (Pyruvate Kinase)

—> produce ATP by cleavage high energy phosphate bond in these substrate
***—> substrate level phosphorylation (Independent on OXYGEN)

Question 5

How oxidative phosphorylation produce ATP

Answer 5

Oxidation of FADH2 and NADH —> produce H gradient across mitochondrial membrane —> drive ATP synthase

1. 2,4-dinitrophenol, Pentachlorophenol: Uncoupling agent transmembrane H carrier
   —> dissipate H gradient
   2 Cyanide, Carbon monoxide: prevent electron flow

Overall effect: dercrease in oxidation of NADH and FADH2 lead to accumulation of:

• pyruvate —> lactate
• fatty acid —> TAG

Question 6

Regulation of Glycolysis (PFK1,2 + pyruvate kinase)

Answer 6

***1. PFK1,2 (F-6-P —> F-1,6-BP)
(stimulated by AMP, insulin, F-2,6-BP, inhibited by ATP, glucagon)
- Insulin —(removal of phosphate from PFK2) —> dephosphorylated PFK2 —> F-2,6-BP —> PFK1 —> F-1,6-BP
- Glucagon —(addition of phosphate to PFK2) —> phosphorylated PFK2 - -> F-2,6-BP —> PFK1 —> F-1,6-BP

2. Pyruvate kinase (Phosphoenolpyruvate—> Pyruvate)
   (stimulated by AMP, insulin, F-1,6-BP, inhibited by ATP, glucagon, Alanine)
   - Insulin —(removal of phosphate from PK)—> active pyruvate kinase —> phosphoenolpyruvate—> pyruvate
   - Glucagon —(addition of phosphate to PK) —> phosphorylated PK - -> phosphoenolpyruvate—> pyruvate

Question 7

Regulation of Gluconeogenesis

Pyruvate Carboxylase, Phosphoenolpyruvate Carboxykinase, F-1,6-Biphosphatase

Answer 7

1. Pyruvate Carboxylase (Pyruvate —> OAA)
   - stimulate by Acetyl-CoA
2. Phosphoenolpyruvate Carboxykinase (OAA —> Phosphoenolpyruvate)
   - gene transcription stimulated by glucagon / inhibited by insulin
3. F-1,6-Biphosphatase (F-1,6-BP —> F-6-P)
   - inhibited by F-2,6-BP

Question 8

Regulation of Glycogenolysis and Glycogenesis

Answer 8

Glycogen phosphorylase (Glycogen —> G-1-P): stimulated by glucagon, inhibited by insulin

Glycogen synthase (G-1-P —> Glycogen): stimulated by insulin, inhibited by glucagon