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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




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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

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Citric Acid Cycle

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 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

 $"!#  5

  

  

 Conversion of citrate to
isocitrate makes the
molecule susceptible to
decarboxylation
 Both steps catalysed by
aconitase

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!
 #  



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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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