2. Glycolysis 1. From glucose to pyruvate; 2. 10-step reactions; 3
Glycolysis 1. From glucose to pyruvate; step reactions; 3. Three inreverseable reactions hexokinase phosphofructokinase pyruvate kinase 4. Rate limiting enzyme: phosphofructokinase-1 5. Production: ATP (net) NADH + H 6. Function: Supply energy in anaerobic condition.

3. Glycolysis in red blood cells
1. Relies exclusively on glycolysis as
fuel to produce ATP;
2. End product is lactate;
3. Produce 2,3-BPG enhancing the
ability of RBCs to release oxygen.

4. The Citric Acid Cycle Kreb’s Cycle Tricarboxylic acid cycle (TAC)
“The wheel is turnin’ and the sugar’s a burnin’”
More than 95% of the energy for the human being is generated through this pathway (in conjunction with the oxidative phosphorylation process)

5. What happened for 2 pyruvates?
Basically three options depending on the environmental conditions

6. From pyruvate to acetyl-CoA
Pyruvate + CoA + NAD Acetyl-CoA + CO2 + NADH + H+
Pyruvate produced from glycolysis must be decarboxylated to acetyl CoA before it enters TCA cycle.
Key irreversible step in the metabolism of glucose.

7. Reaction irreversible
Catalytic
cofactors
Pyruvate is first transported into mitochondria via a specific transporter on the inner membrane and then oxidized to acetyl-CoA by the catalysis of pyruvate dehydrogenase complex.

8. Pyurvate dehydrogenase complex

9. Acetyl-CoA: fuel for the Citric Acid Cycle
Coenzyme A was first discovered by Lipmann in 1945.

10. Lipoate

11. FAD

12. Nicotinamide Adenine Dinucleotide (NAD)
Reduction
Oxidation
Used primarily in the cell as an electron carrier to mediate numerous reactions

15. Oxidization of acetyl-CoA

16. Control of the Pyruvate Dehydrogenase Complex
Regulation by its products
NADH & Acetyl-CoA: inhibit
NAD+ & CoA: stimulate
Regulation by energy charge
ATP : inhibit
AMP: stimulate

17. The citric acid cycle consists of eight successive reactions

18. Step 1: citrate formation
Enzyme: Citrate synthase

19. Step 2: Citrate isomerized to isocitrate
Dehydration
Hydration
Enzyme: aconitase

20. Step 3: Isocitrate to -ketoglutarate
1st CO2 removed
1st NADH produced
Enzyme: isocitrate dehydrogenase

21. Step 4: Succinyl-CoA formation
2nd NADH produced, 2nd CO2 removed
Enzyme: -ketoglutarate dehydrogenase

22. Step 5: Succinate formation
Enzyme: succinyl-CoA synthetase
A GTP (ATP) produced

23. Steps 6: Fumarate formation
Enzyme: Succinate dehydrogenase
A FADH2 produced

24. Steps 7: Malate formation
Enzyme: fumarase

25. Step 8: Malate to Oxaloacetate
3rd NADH produced
Enzyme: malate dehydrogenase

26. Citric Acid Cycle: Overview
Input: 2-carbon units
Output: 2 CO2
1 GTP
3 NADH: 2.5X3=7.5 ATP
1 FADH2: 1.5X1=1.5 ATP
Total: ATP

27. Biosynthetic roles of the citric acid cycle

28. Summary Pyruvate is converted to acetyl-CoA by the action of
pyruvate dehydrogenase complex, a huge enzyme
complex.
Acetyl-CoA is converted to 2 CO2 via the eight-step
citric acid cycle, generating three NADH, one FADH2,
and one ATP (by substrate-level phophorylation).
Intermediates of citric acid cycle are also used as
biosynthetic precursors for many other biomolecules,
including fatty acids, steroids, amino acids, heme,
pyrimidines, and glucose.

29. In carbohydrate metabolism:
Why is citric acid cycle so important?
Citric acid cycle is of central importance in all living cells that use oxygen as part of cellular respiration.
In aerobic organisms, the citric acid cycle is part of a metabolic pathway involved in the chemical conversion of carbohydrates, fats and proteins into carbon dioxide and water to generate energy.
In addition, it provides precursors for synthesis of many compounds including some amino acids.
In carbohydrate metabolism:
1. Glycolysis to produce pyruvate;
2. Pyruvate is oxidized to acetyl-CoA;
3. Acetyl-CoA enters the citric acid cycle.

30. In protein catabolism:
1. Proteins are broken down by proteases into their constituent amino acids.
2. The carbon backbone of these amino acids are converted to acetyl-CoA and entering into the citric acid cycle.
In fat catabolism:
1. Triglycerides are hydrolyzed to into fatty acids and glycerol.
2. In the liver the glycerol can be converted into pyruvate.
3. Fatty acids are broken down through a process known as beta oxidation which results in acetyl-coA which can be used in the citric acid cycle.

31. Regulation of Citric Acid Cycle
3 control sites

32. Control of citric acid cycle
Control points:
1. Citrate synthase
2. Isocitrate dehydrogenase
3. - ketoglutarate dehydrogenase

33. Regulation of Citric Acid Cycle Site 1
Acetyl CoA + Oxaloacetate
Citrate
Enzyme: citrate synthase
Inhibited by ATP
Stimulated by ADP

34. Regulation of Citric Acid Cycle Site 2
Isocitrate -Ketoglutarate
Enzyme: isocitrate dehydrogenase
Inhibited by ATP, NADH,
succinyl-CoA
Stimulated by ADP & NAD+

35. Regulation of Citric Acid Cycle Site 3
- ketoglutarate succinyl-CoA
Enzyme:
-ketoglutarate dehydrogenase
Inhibited by ATP, NADH,
succinyl-CoA
Stimulated by ADP & NAD+

36. Aerobic oxidation of glucose

37. Aerobic oxidation of glucose – How many ATP we can get?

38. Total Energy per glucose through aerobic oxidation
Cytosol
2 ATP
2 NADH
NADH in cytosol can’t get into mitochondrion
In eukaryotes two pathways to transfer NADH into MC
transferred to FADH2
get 1.5 ATP/ FADH2
2 X 1.5 ATP = 3 ATP
Or transferred to NADH
Get 2.5 ATP/ NADH
2 NADH X 2.5 ATP= 5 ATP
Total or so either 5 or 7 ATP

39. In mitochondrion: So… Each NADH makes 2.5 ATP Each FADH2 makes 1.5 ATP
GTP = ATP
So…
From pyruvate in mitochondrion
8 NADH X 2.5 ATP = 20 ATP
2 FADH2 X 1.5 ATP= 3 ATP
2 GTP = 2 ATP
TOTAL in mitochondrion ATP