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TCA CYCLE

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TCA CYCLE PRESENTED BY :P.ARSULA PETERBIOCHEMISTRY LECTURERemail:arshu4127@gmail.comSt.Xavier’s catholic nursing college Nagercoil
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Definition:

The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, represents one part of the three- part aerobic cellular respiration pathway. In cellular respiration, a molecule of glucose enters the pathway and adenosine triphosphate (ATP) ultimately gets produced for use as a source of energy to run cellular processes.

the krebs cycle
The Krebs Cycle
  • Occurs in the matrix of the mitochondrion
  • Aerobic phase (requires oxygen)
  • 2-carbon acetyl CoA joins with a 4-carbon compound to form a 6- carbon compound called Citric acid
tca cycle summary
TCA Cycle Summary

1 acetate through the cycle produces 2 CO2, 1 GTP, 3NADH, 1FADH2

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Citric acid (6C) is gradually converted back to the 4-carbon compound

-ready to start the cycle once more

  • The carbons removed are released as CO2

-enzymes controlling this process called decarboxylases

  • The hydrogens, which are removed, join with NAD to form NADH2

-enzymes controlling the release of hydrogen are called dehydrogenases

pyruvate oxidation
Pyruvate Oxidation

Pyruvate + CoA + NAD+

 acetylCoA + CO2 + NADH + H+

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Pyruvate Dehydrogenaseis a large complex:

pyruvate dehydrogenase (E1),

dihydrolipoyl transacetylase (E2),

dihydrolipoyl dehydrogenase (E3)

Requires 5 coenzymes:

TPP, Lipoic Acid, Coenzyme A, FAD, NAD+

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Pyruvate dehydrogenase Complex (PDC)

  • It is a multi-enzyme complex containing three enzymes associated together non-covalently:
  • E-1 : Pyruvate dehydrogenase , uses Thiamine pyrophosphate as cofactor bound to E1
  • E-2 : Dihydrolipoyl transacetylase, Lipoic acid bound, CoA as substrate
  • E-3 : Dihydrolipoyl Dehydrogenase FAD bound, NAD+ as substrate
  • Advantages of multienzyme complex:
  • Higher rate of reaction: Because product of one enzyme acts as a substrate of other, and is available for the active site of next enzyme without much diffusion.
  • Minimum side reaction.
  • Coordinated control.
reaction 1 citrate synthase
Reaction 1: Citrate Synthase

A thioester: so a high energy compound Hydrolysis helps drive this reaction forward

Allosteric,

-ATP,NADH,

succinyl-CoA

reaction 2 aconitase
Reaction 2: Aconitase

Dehydration followed by hydration

reaction 3 isocitrate dehydrogenase
Reaction 3: Isocitrate Dehydrogenase

FirstOxidative decarboxylation

Allosteric enzyme

-ATP,NADH

reaction 4 ketoglutarate dehydrogenase
Reaction 4: -Ketoglutarate Dehydrogenase

SecondOxidative decarboxylation

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Reaction 5:

Succinyl CoA synthatse:Sccinyl CoA, like Acetyl CoA has a thioester bond with very negative free energy of hydrolysis. In this reaction, the hydrolysis of the thioester bond leads to the formation of phosphoester bond with inorganic phosphate. This phosphate is transferred to Histidine residue of the enzyme and this high energy, unstable phosphate is finally transferred to GDP resulting in the generation of GTP.

reaction 6 succinate dehydrogenase
Reaction 6: Succinate Dehydrogenase

Oxidation

2

e- carrier is FAD

succinate dehydrogenase
Succinate Dehydrogenase
  • Part of electron transport chain in the inner membrane of mitochondria.
  • Removal of H across a C-C bond is not sufficiently exergonic to reduce NAD+,but it does yield enough energy to reduce FAD.
  • Malonate is a competitive inhibitor
reaction 7 fumarase
Reaction 7: Fumarase

Hydration

trans-addition of the elements of water across the double bond, forms L-malate

reaction 8 malate dehydrogenase
Reaction 8: Malate Dehydrogenase

Oxidation

This and the previous two reactions form a reaction triad

+

tca cycle summary22
TCA Cycle Summary

1 acetate through the cycle produces 2 CO2, 1 GTP, 3NADH, 1FADH2

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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

energetics
Energetics
  • Energy is conserved in the reduced coenzymes NADH, FADH2 and one GTP
  • NADH, FADH2 can be oxidized to produce ATP by oxidative phosphorylation

1.5

1.5

7.5

ETS

1.5

7.5

7.5

atp energy from glycolysis aerobic
ATP Energy from Glycolysis(Aerobic)
  • In the electron transport system

NADH = 3 ATP

FADH2 = 2 ATP

  • Glycolysis

Glucose 2 pyruvate + 2 ATP + 2 NADH

NADH in cytoplasm FADH2 mitochondria

Glucose 2 pyruvate + 8 ATP

atp energy from pyruvate
ATP Energy from Pyruvate

2 pyruvate 2 acetyl CoA + 2 CO2 + 2 NADH

2 pyruvate 2 acetyl CoA + 2 CO2 + 6 ATP

atp energy from citric acid cycle
ATP Energy from Citric Acid Cycle

One turn of the citric acid cycle

3 NADH x 3 ATP = 9 ATP

1 FADH2 x 2 ATP = 2 ATP

1 GTP x 1 ATP = 1 ATP

Total = 12 ATP

Glucose provides two acetyl COA molecules for two turns of citric acid cycle

2 acetyl CoA 24 ATP + 4 CO2

atp from glucose
ATP from Glucose

For 1 glucose molecule undergoing complete oxidation

Glycolysis8ATP

2 Pyruvate to 2 Acetyl CoA 6 ATP

2 Acetyl CoA to 4 CO224 ATP

Glucose + 6 O2 6 CO2 + 6 H2O + 38 ATP