1. Oxidative Decarboxylation of Pyruvate
- Pyruvate Dehydrogenase complex is a large multi-subunit complex located in the mitochondria
Irreversible reaction; Acetyl CoA cannot be converted into pyruvate
Pyruvate dehydrogenase is not a part of citric acid cycle but it a major source of fuel for citric acid cycle which is Acetyl CoA
Pyruvate Dehydrogenase complex is aggregate of three enzymes:
1- Pyruvate dehydrogenase component called (pyruvate decarboxylase)
2- Dihydrolipoyl transacetylase
3- Dihydrolipoyl dehydrogenase
Each subunit of this large complex catalyzes a part of the overall reactions.

2. The citric acid cycle oxidizes two carbon units
The citric acid cycle oxidizes two carbon units. These enter the cycle as Acetyl-CoA

3. Regulation Pyruvate Dehydrogenase complex
Product inhibition
The enzyme complex is inhibited by Acetyl CoA when it is accumulated; the production rate is higher than the cell capacity of oxidation with citric acid cycle
High NADH/NAD+ ratio inhibits this enzyme complex
Covalent modification
Two forms of the enzyme complex;
Active non- phosphorylated form
Inactive phosphorylated
The two forms can be interconverted by the action of two enzymes phosphatase and kinase
The kinase is activated by an increase in the ratio of acetyl CoA/ CoA ratio or NADH/ NAD+.
elevated ADP\ATP ratio  demand for energy  inhibits the kinase and activate the phosphatase to produce more of the active non-phosphorylated enzymes

4. Regulation Pyruvate Dehydrogenase complex
Pyruvate Dehydrogenase is regulated both allosterically and by reversible phosphorylation

5. The Citric acid cycle
- Citric acid cycle contains a series of oxidation-reduction reactions
- Carbon entering the cycle, leaves fully oxidized as CO2.
- “High energy” electrons leave the cycle with high energy electron carriers as NADH and FADH2.
- Very little ATP is made directly in the cycle.
- No oxygen is used in the cycle.
Overall reaction
3NAD+ + FAD + GDP + Pi + 2H2O + acetyl-CoA
3NADH + FADH2 + GTP + CoA + 2CO2 + 3H+

6. Krebs cycle, tricarboxylic acid cycle TCA
Citric acid cycle
Krebs cycle, tricarboxylic acid cycle TCA
The central function is the oxidation of acetyl CoA to CO2
It is the final common pathway for oxidation of fuel molecules
Acetyl Co is derived from the metabolism of fuel molecules as amino acids, fatty acids, and carbohydrates.
Citric acid cycle is also an important source of precursors
Some intermediates are precursors of amino acid
One of the intermediates is used in the synthesis of porphorins
Another is used in the synthesis of fatty acids and sterols.
Citric Acid Cycle located in the mitochondrial matrix

8. Citric acid cycle is also an important source of precursors for biosynthetic reactions

9. Citric acid cycle intermediates are always in flux

12. 4C 6C 6C 5C 4C

14. The Citric acid cycle

15. The Citric acid cycle

16. The Citric acid cycle

17. The Citric acid cycle

18. Control Points in the Citric Acid Cycle
IDH catalyzes the rate-limiting step
Regulation of the TCA cycle occurs at both the level of entry of substrates into the cycle as well as at the key reactions of the cycle.
Fuel enters the TCA cycle primarily as acetyl-CoA.
The generation of acetyl-CoA from carbohydrates is, therefore, a major control point of the cycle.
This is the reaction catalyzed by the PDH complex.

19. Control Points in the Citric Acid Cycle

20. Single molecule of glucose can potentially yield ~38 molecules of ATP

21. The end

23. Regulation of Pyruvate Dehydrogenase
Pyruvate Dehydrogenase is regulated both allosterically and by reversible phosphorylation

24. Cofactors for the Pyruvate Dehydrogenase include
CoA-SH, NAD+, TPP, FAD, Lipolate

25. Oxidative Decarboxylation of Pyruvate occurs in multi-step reactions
E1: Pyruvate dehydrogenase
E2: Dihydrolipoyl transacetylase
E3: Dihydrolipoyl dehydrogenase