CHEM 445 / BIOL 445
Biochemistry II

J. D. Cronk
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21. header

Lecture 21. Fatty acid metabolism: Synthesis

Friday 9 March 2007

Ketone bodies: Utilization of acetoacetate. Fatty acid synthesis - general features. Fatty acid synthase: a multifunctional enzyme complex and the structural features of fatty acid synthesis. Sources of NADPH.

Reading: BTS6, Ch.22, pp.631-640.

 

21. Summary

Lecture 21 Summary

Ketone bodies and acetoacetate metabolism

The formation of acetoacetate provides an alternate way of mobilizing two-carbon units in soluble form for distribution to peripheral tissues. This synthesis of so-called "ketone bodies", mostly in the form of acetoacetate, is performed mainly by the liver. We refer to this as a "synthesis" since the product is built up starting from two molecules of acetyl CoA. Acetooacetate is a soluble 4-carbon unit that can be carried in the bloodstream, much like glucose.

Fatty acid synthesis: Key points

¶ The synthesis of saturated, C16 fatty acid (palmitate) requires eight enzyme-catalyzed reactions: the seven listed in Table 22.2, p.636, BTS6) - which includes acetyl CoA carboxylase - plus the release of palmitate catalyzed by palmitoyl thioesterase.

¶ These enzymes are separable polypeptide chains in E. coli, but in eukaryotes these enzymatic activities (excepting acetyl CoA carboxylase) reside within one or two large protein molecules that form multifunctional complexes.

¶ Formally the reverse of fatty acid oxidation, fatty acid synthesis is a distinct pathway that differs from the latter in five principal respects (see table below).

Table: Principal differences between fatty acid synthesis and degradation


 
fatty acid synthesis fatty acid degradation  

 
subcellular localization cytosol mitochondrial matrix  
electron donor/acceptor NADPH FAD and NAD+  
acyl group carrier acyl carrier protein (ACP) coenzyme A  
C2 unit donor/product malonyl CoA acetyl CoA  
stereochemistry of 3-hydroxyacyl intermediate D L  

 

 


Study questions

  • What are ketone bodies and what is their significance?
  • Summarize the differences between b-oxidation, fatty acid synthesis in E. coli.
  • Summarize the differences between fatty acid synthesis in E. coli, in yeast, and in mammals.
  • Explain the advantages of a multifunctional enzyme complex.

Page updated 12-27-06

References

1. Berg, Tymoczko, and Stryer. Biochemistry (BTS): 6th edition (2007, Freeman) Ch.22, pp.631-640.

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