Part 5

Metabolic Pathways and ATP

Synthesis
Dr Lynette Brownfield

Lecture 29
Citric Acid Cycle

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Pathways for processing food molecules for ATP synthesis

Fuel molecules




-oxidation





2
KREBS CYCLE / TCA CYCLE / CITRIC ACID
CYCLE (CAC)
glucose fatty acids

The CAC
occurs in the
mitochondria

All but one
reaction occurs in
the mitochondrial
matrix

3
Citric Acid Cycle

4
  


 

 

2 carbon acetyl-CoA is attached to 4 carbon oxaloacetate

Energy for the reaction comes from the hydrolysis of CoA
from acetyl-CoA

Because the CAC is a
cycle these two carbons need to
be removed

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5
 




  

Conversion of citrate to
isocitrate makes the
molecule susceptible to
decarboxylation

Both steps catalysed by
aconitase

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Fluoroacetate is metabolised to fluorocitrate

Fluorocitrate binds to and inhibits aconitase
(citrate to isocitrate)
 


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Conversion of citrate to
isocitrate makes the
molecule susceptible to
decarboxylation

Both steps catalysed by
aconitase

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An oxidative decarboxylation

Reaction occurs in two steps: oxidation then
decarboxylation

Energy conserved in NADH

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Another oxidative decarboxylation

Catalysed by -ketoglutarate dehydrogenase

Very similar to the pyruvate dehydrogenase reaction

Energy conserved as NADH





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Citric Acid Cycle summary of the first half

Two carbons have been
removed

Energy been conserved as
NADH

A four carbon molecule has
been regenerated
(succinyl-CoA)

The rest of the cycle is

concerned with regenerating
oxaloacetate (our starting point)
from succinyl-CoA

There are many similarities
between these reactions and
those of -oxidation
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The conversion of succinyl-CoA to succinate is like the
activation of fatty acids in reverse

The removal of the CoA releases enough energy to drive
the synthesis of GTP
GTP + ADP GDP + ATP

The 3rd substrate level phosphorylation
   

 
  


The DIRECT use of energy from a substrate molecule to
drive the synthesis of ATP (or equivalent)

You will see that oxidative phosphorylation uses the energy from a
substrate molecule INDIRECTLY to drive the synthesis of ATP 14
 



 



The reactions used to

convert succinate to
oxaloacetate are very
similar to -oxidation

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The succinate dehydrogenase (SDH) reaction is shared
between the CAC and the electron transport chain (ETC)

SDH is located in the inner mitochondrial membrane

SDH is part of Complex II of the ETC

Energy conserved in FADH2

succinate + E-FAD fumarate + E-FADH2

(E = SDH) 16
  


acetyl-CoA + 3NAD+ + FAD + 2H2O + GDP + Pi

2CO2 + CoASH + 3NADH + 3H+ + FADH2 + GTP






energy released from the oxidation of acetyl-CoA in the

CAC is conserved as:
3 x NADH
further metabolised
1 x FADH2 in the ETC

1 x GTP (ATP)

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 Pathways for processing food molecules for ATP synthesis

Fuel molecules




-oxidation





 


 




 


 


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