The document outlines the TCA cycle (Krebs cycle), detailing its steps, processes, and significance in energy production through the oxidation of acetyl CoA. It highlights the cycle's role in generating high-energy molecules like NADH and FADH2, as well as its importance in both catabolic and anabolic pathways. The TCA cycle is essential for metabolism, connecting various metabolic pathways and generating simple end products such as CO2 and water.

1. Presented by:
Nursad Jahan Sultana

2. Contents :
Introduction
Site
Pathway
Result
Significance
Conclusion

3. Glucose Fatty acid Amino acid
glycolysis
Pyruvate
Acetyl CoA
TCA Cycle
GTP + CO₂ + NADH & FADH₂ (high energy molecules)
ETC ATP production
Carbohydrate Fat Protein
Metabolism of some important components in our body

4. TCA Cycle:
Tri-carboxylic acid, also known as Citric acid cycle or Krebs cycle.
A series of chemical reaction to generate energy through the
oxidation of Acetyl CoA into CO₂, GTP and NADH & FADH₂.
TCA cycle also provides intermediates required for the synthesis of
amino acids, glucose, heme etc.
Acetyl CoA
CO₂ GTP
NADH
FADH₂

5. Site:
This cycle takes place in the
matrix of mitochondria in
eukaryotes & cytosol in
prokaryotes.
Mitochondria

6. Reactions of
TCA cycle:
Oxidative decarboxylation
of Pyruvate to Acetyl CoA by
PDH complex.
This step is connecting link
between glycolysis & TCA
cycle.

7. Step-1: Formation of citrate:
Oxaloacetate condenses with acetyl CoA to form Citrate, catalyzed
by the enzyme ‘citrate synthase’.
Inhibited by:
ATP, NADH, Citrate - competitive inhibitor of oxaloacetate.
Step-2 & 3: Citrate is isomerized to Isocitrate:
Citrate is isomerized to Isocitrate by the enzyme ‘aconitase’.
This is achieved in a two-stage reaction of dehydration followed by
hydration through the formation of an intermediate -cis- aconitate.

8. Step-4 & 5: Formation of α- ketoglutarate:
‘Isocitrate dehydrogenase’ catalyzes the conversion of isocitrate to
oxalosuccinate & then to α- ketoglutarate.
The formation of NADH & the liberation of CO2 occur at this stage.
Stimulated by:
Isocitrate, 𝑁𝐴𝐷+
, 𝑀𝑔2+
, ADP, 𝐶𝑎2+
Inhibited by:
NADH & ATP.

9. Step-6: Conversion of α- ketoglutarate to succinyl CoA:
Occurs through oxidative decarboxylation, catalyzed by ‘α-
ketoglutarate dehydrogenase’ complex.
“α- ketoglutarate dehydrogenase is a multienzyme complex”
At this stage, second NADH is produced & second CO2 is liberated.
Step-7: Conversion of succinate:
Succinyl CoA is converted to succinate by ‘succinate thiokinase’.
This reaction is coupled with the phosphorylation of GDP to GTP.
GTP is converted to ATP by the enzyme ‘nucleoside diphosphate
kinase’.

10. Step-8: Conversion of succinate to fumarate:
Succinate is oxidized by ‘succinate dehydrogenase’ to fumarate.
This reaction results in the production of FADH2.
Step-9: Formation of malate:
The enzyme ‘fumarase’ catalyzes the conversion of fumarate to
malate with the addition of H2O.

11. Step-10: Conversion of malate to oxaloacetate:
Malate is then oxidized to oxaloacetate by ‘malate dehydrogenase’.
The third & final NADH occurs at this stage. The oxaloacetate is
regenerated that can combined with another molecule of acetyl
CoA and continue the cycle.

12. glycolysis
Glucose (6C) Pyruvate (3C)
Acetyl CoA
Citrate
Isocitrate
Alpha-
Ketoglutate
Succinyl
CoA
Succinate
Fumarate
Malate
Oxaloacetate
NAD
NADH
CO₂
NAD
NADH
CO₂
GTP
FADH₂ FAD
NADH
NAD
Citrate synthase Aconitase
Isocitrate dehydrogenase
-Ketoglutarate
dehydrogenase
Succinyl CoA synthase
Succinate
dehydrogenase
Fumarase
6C
2C
4C
TCA Cycle Pathway

13. Result of Krebs Cycle:
3xNADH
1xFADH₂
1xGTP
2xCO₂
6xNADH
2xFADH₂
2xGTP
4CO₂

14. Significance
of TCA Cycle:
ATP generation
Synthesis of NADH & FADH2
Complete & final oxidation of 2C acetyl
CoA in the aerobic respiration.
Simple & harmless end products
such as CO2 & H2O.
Many important 4C, 5C & 6C organic
acids as intermediates.

15. Amphibolic
nature of
TCA cycle:
TCA cycle is both
catabolic & anabolic in
nature, called
amphibolic.
Since various compounds
enter or leaves from TCA
cycle, it is sometimes
called as metabolic traffic
circle.

16. Important anabolic reactions of TCA Cycle:
Oxaloacetate is precursor for aspartate.
α- ketoglutarate can be transaminated to glutamate.
Succinyl CoA is used for synthesis of heme.
Mitochondrial citrate is transported to cytoplasm and it is cleaved into
acetyl CoA to provide substrate for fatty acid synthesis.

17. Improper Occurrence of TCA Cycle:
No ATP No NADH
& FADH2
No CO2 No ATP

18. Conclusion:
TCA cycle is one of the most important
reactions that takes place in both
Eukaryotes and Prokaryotes. It is the
most important central pathway,
connecting almost all the individual
metabolic pathways.

19. Thank You