The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle[1][2] – is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins, into adenosine triphosphate (ATP) and carbon dioxide. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions.

1. CITRIC ACID CYCLE
Faslu Rahman CK
CVAS Pookode

2. Reactions of Glycolysis are localized in
Cytosol, and do not require any oxygen.
whereas pyruvate dehydrogenase and TCA
cycle reactions take place in mitochondria
where oxygen is utilized to generate ATP by
oxydative phosphorylation.
Consumption of oxygen (respiration)
depends on the rate of PDC and TCA
reactions.

3. In Mitochondria
In Cytosol

4. History
• Sir Hans A.Krebs studied condensation of oxaloacetate
with acetyl CoA to form one tricarboxylic acid.
• He received nobel prize in 1953.
• Ogsten and potter showed that TCA formed was citric acid
.

5. • It act as source of significant fraction of
reduced coenzymes that drive the respiratory
chain.
• Components of the cycle have a direct or
indirect controlling effects on key enzymes of
other pathways.

7. Conversion of pyruvate to Acetyl CoA
CH3
O
O
O
pyruvate
CO2HSCoA
CH3
SCoA
O
acetyl CoA
NADHNAD+
pyruvate dehydrogenase complex
• 2 per glucose (all of Kreb’s)
• Oxidative decarboxylation
• Makes NADH
• -33.4kJ

8. 8
Pyruvate dehydrogenase multienzyme
complex
• Pyruvate dehydrogenase - E1
• Pyruvate + TPP –> Hydroxyethyl TPP + CO2
• Dihydrolipoyl transacetyase - E2
• HOEt-TPP + lipoamide–> Acetyl-dihydrolipoamide + TPP
• Acetyl-dihydrolipoamide + CoA-SH –> acetyl CoA +
dihydrolipoamide
• Dihydrolipoyl dehydrogenase - E3
• NAD+ + dihydrolipoamide –> NADH + H+ + lipoamide

10. Citrate Synthase Reaction (First)
acetyl CoA oxaloacetate
CoASH
citrate synthase
citrate
OH2
CH3
C
O
SCoA
C O
CH2
C
O
C
OO
O
C
OO
CH2
C
CH2
C
OH C O
O
O O
+
• Claisen condensation
• -32.2kJ

11. Aconitase Reaction
citrate
aconitase
isocitrate
C
OO
CH2
C
CH2
C
OH C O
O
O O
C
OO
CH
CH
CH2
C
C O
O
OO
OH
• Forms isocitrate
• Goes through alkene intermediate (cis-aconitate)
• elimination then addition
• Hydroxyl moved and changed from tertiary to secondary
• (can be oxidized)
• 13.3kJ

12. Isocitrate Dehydrogenase
isocitrate
NAD NADH CO2
isocitrate dehydrogenase
alpha ketoglutarate
C
OO
CH
CH
CH2
C
C O
O
OO
OH
C
OO
C
CH2
CH2
C
OO
O
• All dehydrogenase reactions make NADH or FADH2
• Oxidative decarboxylation
• -20.9kJ
• Energy from increased entropy in gas formation

13. α-ketoglutarate dehydrogenase
• Same as pyruvate dehydrogenase reaction
• Formation of thioester
• endergonic
• driven by loss of CO2
• increases entropy
• exergonic
• -33.5kJ

14. Succinyl CoA synthetase
succinyl CoA
GDP GTP CoASH
succinate
succinyl CoA
synthetase
C
CH2
CH2
C
OO
OSCoA
C
CH2
CH2
C
OO
O
O
• Hydrolysis of thioester
• Releases CoASH
• Exergonic
• Coupled to synthesis of GTP
• Endergonic
• GTP very similar to ATP and interconverted later
• -2.9kJ

15. Succinate dehydrogenase
succinate
FAD FADH2
succinyl CoA
dehydrogenase
fumarate
C
CH2
CH2
C
OO
O
O
C
C
C
C
OO
O O
H
H
• Dehydrogenation
• Uses FAD
• NAD used to oxidize oxygen-containing groups
• Aldehydes
• alcohols
• FAD used to oxidize C-C bonds
• 0kJ

16. Fumarase
fumarate
OH2
malate
fumarase
C
C
C
C
OO
O O
H
H
C
CH
CH2
C
OO
O
OH
O
• Addition of water to a double bond
• -3.8kJ

17. Malate Dehydrogenase
oxaloacetate
malate
NAD NADH
malate
dehydrogenase
C
CH
CH2
C
OO
O
OH
O
C O
CH2
C
O
C
OO
O
• Oxidation of secondary alcohol to ketone
• Makes NADH
• Regenerates oxaloacetate for another round
• 29.7 kJ

18. 18
CitricAcid Cycle
H3C C
O
COO-H3C C
O
S CoA
C
CH2
COO-
COO-
O
CH
CH2
COO-
COO-
CH
CH
COO-
COO-
HO
CH2
CH2
COO-
COO-
C
CH2
COO-
COO-
CH2
COO-
HO
CH
CH
COO-
COO-
CH2
COO-
HO
CH2
C
COO-
CH2
COO-
O
CH2
C
S
CO2
CH2
COO-
O
CoA
CO2
CO2

19. 19
CitricAcid Cycle
intermediates H3C C
O
COO-H3C C
O
S CoA
C
CH2
COO-
COO-
O
CH
CH2
COO-
COO-
CH
CH
COO-
COO-
HO
CH2
CH2
COO-
COO-
C
CH2
COO-
COO-
CH2
COO-
HO
CH
CH
COO-
COO-
CH2
COO-
HO
CH2
C
COO-
CH2
COO-
O
CH2
C
S
CO2
CH2
COO-
O
CoA
CO2
CO2
Oxaloacetate
Citrate
Isocitrate
a-ketoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
Pyruvate
Acetyl-CoA

20. Regulation of CAC:
Rate controlling enzymes:
Citrate synthatase
Isocitrate dehydrogenase
a-keoglutaratedehydrogenase
Regulation of activity by:
Substrate availability
Product inhibition
Allosteric inhibition or activation by
other intermediates

21. THANKYOU