1. بسم الله الرحمن الرحيم

2. Glycolysis By Amr S. Moustafa, M.D.; Ph.D.
Assistant Prof. & Consultant, Medical Biochemistry Dept.
College of Medicine, KSU

3. Glucose Transport Na+-Independent Facilitated Diffusion
Glucose Transporters (GLUT 1-14)
With concentration gradient
Energy Independent
Na+-Monosaccharide Cotransporter:
Against concentration gradient
Energy dependent
Carrier-mediated (SGLT)
Coupled to Na+ transport
Small intestine, renal tubules & choroid plexus

4. Glucose Transport: Facilitated Diffusion

5. Glucose Transporters Tissue-specific expression pattern
GLUT-1 RBCs and brain
GLUT-2 Liver, kidney & pancreas
GLUT-3 Neurons
GLUT-4 Adipose tissue & skeletal muscle
GLUT-5 Small intestine & testes
GLUT-7 Liver (ER-membrane)
Functions:
GLUT-1, 3 & 4 Glucose uptake from blood
GLUT-2 Blood & cells (either direction)
GLUT-5 Fructose transport

6. Glucose Transport & Insulin

7. Metabolic Pathway Definition Site: Cellular (tissue) and Subcellular
Reactions
Rate-limiting enzyme(s)
Regulatory mechanism(s):
Rapid, short-term:
Allosteric Covalent modification
Slow, long-term:
Induction/repression

8. Glycolysis

9. Aerobic Vs Anaerobic Glycolysis

10. Aerobic Glycolysis: Total Vs Net ATP Production

11. Aerobic Glycolysis-1
Hexokinase
Glucokinase

12. Aerobic Glycolysis-2

13. Aerobic Glycolysis: 3-5

14. 2 2
Aerobic Glycolysis: 6 -10 2 2 2 2

15. Aerobic Glycolysis-1
Hexokinase
Glucokinase

16. Hexokinase Vs Glucokinase
Site
Most tissues
Hepatocytes
Islet cells (pancreas)
Kinetics
Low Km
Low Vmax
High Km
High Vmax
Regulation
G-6-phosphate
F-6-phosphate
Insulin: Induction
Function
Low glucose conc.
High glucose conc.
Glucose sensor

17. Hexokinase Vs Glucokinase -2

18. Glucokinase Regulatory Protein

19. PFK-1 : Regulation

20. F – 2,6 – Bisphosphate and PFK-2

21. Aldolase and Triose Isomerase

22. Glyceraldehyde 3-Phosphate Dehydrogenase2 2 2 2 2 2

23. Phospho- glycerate Kinase2 2
Phospho- glycerate Kinase
Substrate-
Level
Phosphorylation 2 2 2 2

24. 2 2 2
Substrate-
Level
Phosphorylation 2 2
Pyruvate Kinase 2

25. Pyruvate Kinase Covalent Modification

26. Pyruvate Kinase Deficiency Hemolytic Anemia

27. Summary: Regulation of Glycolysis
Regulatory Enzymes (Irreversible reactions):
Glucokinase/hexokinase
PFK-1
Pyruvate kinase
Regulatory Mechanisms:
Rapid, short-term:
Allosteric
Covalent modifications
Slow, long-term:
Induction/repression
Apply the above mechanisms for each enzyme where applicable

28. Aerobic Glycolysis: ATP Production
ATP Consumed:
2 ATP
ATP Produced:
Substrate-level 2 X 2 = 4 ATP
Oxidative-level 2 X 3 = 6 ATP
Total ATP
Net: – 2 = 8 ATP

29. Shuttle Mechanisms 2 ATP 3 ATP A. Glycerol-phosphate Shuttle
B. Malate - Aspartate
Shuttle
3 ATP

30. Anaerobic Glycolysis

31. Lactate Dehydrogenase

32. Lactate Consumption Lactate Pyruvate LD NAD+ NADH
Liver: Pyruvate to glucose (Gluconeogenesis)
Pyruvate to active acetate (CO2 + H2O, Krebs)
Heart: Pyruvate to active acetate (CO2 + H2O, Krebs)

33. Lactate Lactate in muscle: Muscle cramps
Lactate in blood: Lactic acidosis
Blood lactate level: Monitors patient’s recovery
Oxygen debt

34. Anaerobic Glycolysis: ATP Production
ATP Consumed:
2 ATP
ATP Produced:
Substrate-level 2 X 2 = 4 ATP
Oxidative-level 2 X 3 = 6 ATP
Total ATP
Net: – 2 = 2 ATP

35. Anaerobic Glycolysis: RBCs 2,3-BPG Shunt

36. Glycolysis in RBCs: ATP Production
ATP Consumed:
2 ATP
ATP Produced:
Substrate-level 2 X 2 = 4 ATP
1 X 2 = 2 ATP
Oxidative-level 2 X 3 = 6 ATP
Total ATP
Net: – 2 = 2 ATP
2 – 2 = 0 ATP OR OR

37. Glycolysis in RBCs: Summary
End product:
Lactate
No net production or consumption of NADH
Energy yield:
No 2,3-BPG 2 ATP
2,3-BPG shunt 0 ATP
PKD hemolytic anemia depends on:
Degree of PKD
Compensation by 2,3-BPG