p
 



 
p
 


 
„ Fatty acids are synthesized by an a
 

  
a,
which is responsible for the complete synthesis of palmitate from
acetyl-CoA in the cytosol.
„ Jn most mammals, glucose is the primary substrate for lipogenesis,
but in ruminants it is acetate, the main fuel molecule produced by
the diet.
„ Jn birds, lipogenesis is confined to the liver, where it is particularly
important in providing lipids for egg formation.
¦
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¦
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¦
¦

„ ¦his system is present in many tissues, including

liver,kidney, brain, lung, mammary gland, and adipose
tissue.
„ Jts cofactor requirements include NADPH, A¦P, Mn2+,
biotin, and HCO3ð (as a source of CO2).
„ a
 is the immediate substrate, and free
palmitate is the end product.


 
  
a  
  
  
a 




a

„ picarbonate as a source of CO2 is required in the initial reaction for the

carboxylation of acetyl-CoA to    in the presence of A¦P and
a
  a
„ Acetyl-CoA carboxylase has a requirement for the vitamin 
 
„ ¦he enzyme is a 
a  a 
a containing a variable number of
identical subunits, each containing biotin, biotin carboxylase, biotin
carboxyl carrier protein, and transcarboxylase, as well as a regulatory
allosteric site.
„ ¦he reaction takes place in two steps: (1) carboxylation of biotin involving
A¦P and (2) transfer of the carboxyl to acetyl-CoA to form malonyl-CoA.
p
 


 
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„ ¦a 



a a  aa
aa

a 
a
„ ¦hrough outthe process, the intermediates remain covalently
attached as thioesters to one of two thiol groups of the
synthase complex. One point of attachment is the -SH group
of a Cys residue in one of the seven synthase proteins
(beta -ketoacyl-ACP synthase); the other is the -SH group of
acyl carrier protein.
„   a 
a   Ô





a

  







a
a a
„ ¦he 4-phosphopante-theine prosthetic group of ACP is
believed to serve as a flexible arm, tethering the growing
fatty acyl chain to the surface of the fatty acid synthase
complex while carrying the reaction intermediates from one
enzyme active site to the next.

 
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„ pefore the condensation reactions that build up the fatty
acid chain can begin, the two thiol groups on the enzyme
complex must be charged with the correct acyl groups.
„ First, the acetyl group of acetyl- CoA is transferred to the
Cys -SH group of the - ketoacyl-ACP synthase. ¦his reaction
is catalyzed by acetyl-CoA²ACP transacetylase ,¦he second
reaction, transfer of the malonyl group from malonyl-CoA to
the -SH group of ACP, is catalyzed by malonyl-CoA²ACP
transferase , also part of the complex.
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„ º


  
 



 







of a fatty acid chain is condensation of the activated acetyl
and malonyl groups to form a
a

Jn this
reaction, catalyzed by a
a
  
a 
 
„ º


 




 





 ACP formed in the condensation step now
undergoes reduction of the carbonyl group at C-3 to form D-
- hydroxybutyryl-ACP. ¦his reaction is catalyzed by 
a
  a

a 
 

a aa


  is NADPH.
„ º


 



 







  
from C-2 and C-3 of D--hydroxybutyryl-ACP to
yield a double bond in the product, à
 à
 ACP.
¦he enzyme that catalyzes this dehydration is - hydroxyacyl-
ACP dehydratase (HD).
„ º

!
 





" 
2 

 à  
bond of à
à
   
à
à to form
butyryl-ACP by the action of enoyl-ACP reductase (ER);
again, NADPH is the electron donor.
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„ Nearly all the acetyl- CoA us Jntramitochondrial acetyl-CoA
first reacts with oxaloacetate to form citrate, in the citric
acid cycle reaction catalyzed by 

a 
a 
„ Citrate then passes through the inner membrane on the
citrate transporter. Jn the cytosol, citrate cleavage by 

a
 a regenerates acetyl-CoA in an A¦Pdependent reaction.
ed in fatty acid synthesis is formed in mito-

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