Biochemistry under metabolism

1. The Glycolytic pathway
Likando Chababa, 2024
M.Sc Biochemistry (UNZA)

2. Outline of Catabolic Pathways

3. Carbohydrate Metabolism

4. Glucose Metabolism at Subcellular Level
CYTOSOL
MITOCHONDRION
CYTOSOL
MITOCHONDRION
CYTOSOL
MITOCHONDRION

5. Fates of Glucose

6. Reactions of Glycolysis

7. The pathway

10. Step 1: Phosphorylation of Glucose
Nucleophilic attack of the C6 –
OH group of glucose on the 
phosphate of an Mg-ATP
..
Kinase: Enzyme that transfers phosphoryl groups between ATP and
metabolite
First ATP
Utilization

11. Step 2: Conversion of glucose 6-phosphate to fructose
6-phosphate

12. Step 3: Phosphorylation of fructose 6-phosphate to
fructose 1,6-bisphosphate
Second ATP utilization

13. Step 4: Cleavage of fructose 1,6-bisphosphate

14. Step 4: Cleavage of fructose 1,6-bisphosphate

15. Step 5: Interconversion of the triose phosphates

16. 3-phosphoglycerate
2-phosphoglycerate
Phosphoenolpyruvate
Pyruvate
1,3-bisphosphoglycerate
Glyceraldehyde 3-phosphate
Payoff or Redox Phase

17. • NAD+
is the primary oxidizing agent of glycolysis
• NADH produced here must be continually reoxidized to keep this pathway
supplied with NAD+
Step 6: Oxidation of glyceraldehyde 3-phosphate to 1,3
bisphosphoglycerate
Compound with high phosphate
group-transfer potential

18. Step 7: Phosphoryl transfer from 1,3-bisphosphoglycerate
to ADP to make ATP
First ATP generation step of glycolysis

19. Step 8: Conversion of 3-phosphoglycerate to 2-phosphoglycerate

20. Step 9: Dehydration of 2-phosphoglycerate to phosphoenolpyruvate

21. Phosphoenolpyruvate , PEP

22. Step 10: Transfer of a phosphoryl group from PEP to
ADP

23. Regulation of Metabolic Reactions

24. Energetics of Glycolysis
The elegant evidence of regulation!
• Standard state G values are scattered:
+ and -
 G in cells is revealing:
– Most values near zero
– 3 of 10 reactions have large, negative G
• Large negative G reactions are sites of
regulation!

25. Regulation of glycolytic pathway

26. Regulation of
Glycolysis

27. Enzyme Inhibitors Activators
Hexokinase G6P
PFK1 ATP, citrate ADP, AMP, F2,6BP, F6P
PK ATP F1,6BP
Some effectors of the regulatory enzymes of
glycolysis

28. inhibition activation
ADP
AD
P
AD
P
ADP
F-1,6-BP
F-1,6-BP
Allosteric enzymes
•F6P binds preferentially to R state
•ATP binds to regulatory site in T state only
•Citrate is an allosteric inhibitor
• F2,6BP is an allosteric activator
PFK-1 and its regulation

29. Complete oxidation of Glucose to CO2

31. Lactic Acid Fermentation
Ethanol Fermentation
Fates of Pyruvate

32. Fates of Pyruvate in Man
2CO2
Cholesterol
CO2
Lactate
Pyruvate
Acetyl CoA
Citric
Acid
Cycle
A
m
i
n
o
A
c
i
d
s
A
m
i
n
o
A
c
i
d
s
Protein Fatty
Acids

33. Anaerobic fates of Pyruvate
Ethanol
fermentation in
yeast and other
microorganisms
Lactic acid fermentation in
several types of animal cells
and some microorganisms