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Citric acid cycle
1. Citric acid cycle or Krebs cycle or
Tricarboxylic acid cycle
• Citric acid cycle is the most important metabolic
pathway for energy supply to the body.
• 70% of the ATP out of total ATP is synthesized in the
cycle out of total ATP .
• Citric acid cycle essentially involves the oxidation of
acetyl CoA to CO2 and H2O.
• The cycle utilizes two third of total oxygen consumed
by the body
Citric acid cycle is the final common oxidative pathway
for carbohydrates fats and amino acids.
2. Central metabolic pathway
• The cycle is not only supplies energy but also
provides many intemediates required for synthesis of
amino acids, glucose , heme etc..
• Krebs cycle is the most important central pathway
connecting almost all the individual metabolic
pathways
• The cycle was proposed by Hans adolf krebs in 1937
• The pathway is located in Mitichondrial Matrix in
close proximity to the electron trasport chain
3. Steps involved in the cycle
Conversion of pyruvate to acetyl CoA
1. Pyruvate dehydrogenase
• Citrate formed from acetyl CoA and Oxaloacetate
4. Conversion of Acetyl CoA to Citrate
2. Citrate synthase
• Addition of C2 unit (acetyl) to the keto double bond of C4
acid, oxaloacetate, to produce C6 compound, citrate
5. Conversion of citrate to isocitrate
3. Aconitase
• Elimination of H2O from citrate to form C=C bond of cis-
aconitate
• • Stereospecific addition of H2O to cis-aconitate to form
isocitrate
6. Conversion of isocitrate to α-ketoglutarate
3. isocitrate dehydrogenase
• Hydride ion from the C-2 of Isocitrate is transferred to NAD+ to
form NADH to form Oxalosuccinate which is decarboxylated to
a-ketoglutarate
7. Conversion of α-ketoglutarate to SuccinylCoA
4. α-ketoglutarate dehydrogenase
• It occurs through the oxidative decarboxylation
• This enzyme is depedent on five cofactors- TPP,
lipoamide,NAD+ , FAD and CoA. Similar to pyruvate
dehydrogenase complex
8. Conversion of succinyl CoA to succinate
5. succinate thiokinase
• Free energy in thioester bond of succinyl CoA is conserved as GTP o
• ATP in higher animals (or ATP in plants, some bacteria)
• Substrate level phosphorylation reaction
9. Conversion of succinate to fumarate
6. Succinate dehydrogenase
• Embedded in the inner mitochondrial membrane
• Electrons are transferred from succinate to FAD and then to
ubiquinone (Q )in electron transport chain
• Dehydrogenation is stereospecific; only the trans isomer is
formed
10. Conversion Fumarate to Malate
7. Fumarase
• Stereospecific trans addition of water to the double bond of
fumarate to form L-malate
• Only the L isomer of malate is formed
11. Conversion of Malate to Oxalosuccinate
• Malate is oxidized to form oxaloacetate
13. Energy caliculations
The events of krebs cycle may be summerized as
AcetylCoA + 3NAD+ + FAD + GDP +Pi +2H2O
2CO2+ 3NADH +3H+ +FADH2+GTP+CoA
3NADH = 9ATP
FADH2 = 2ATP
GTP = ATP
TOTAL = 12ATP
This energy is for utilization of one Acetyl CoA
14. The citric acid cycle is amphibolic
• The cycle is involved in theaerobic catabolism of
carbohydrates, lipids and amino acids.
• Intermediates of the cycle are starting points for many
anabolic reactions
Krebs Cycle is a Source of Biosynthetic Precursors