10 II. BIOSYNTHESIS 



2. The Biosynthesis of Saturated Fat ty Acids 



The remarkable fact that practically all natural fats are composed of 

 fatty acids with even numbers of carbons is convincing evidence that 

 they are synthesized by the condensation of an intermediate containing an 

 even number of carbon atoms. In fats such as butterfat, definite amounts 

 of all of the even-numbered saturated fatty acids from butyric (C4) to 

 arachidic (C20) occur. Since the differences in chain length are stepwise 

 and amount to two carbons each, it is only natural to postulate that a two- 

 carbon compound forms the building stone in the synthesis of the different 

 fatty acids. As early as 1907, Raper^ stated that "the formation of fatty 

 acids in animals, from carbohydrates,. . suggests that these acids are pro- 

 duced by the condensation of some highly reactive substance containing 

 two carbon atoms and formed in the decomposition of sugar." The subject 

 of the synthesis of fat from such two-carbon fragments as acetate has 

 been reviewed by Bloch,^'* by Kleinzeller/ by Popjak,^ and by Folley.^ 

 Medes, Spirtes, and Weinhouse^ described a method for estimating the 

 rate of fattj^ acid synthesis in liver slices, which consists in incubating slices 

 of tissues with labeled acetyl precursors and comparing the specific activi- 

 ties of the acetoacetate and fatty acids. 



(1) Possible Building Stones of Fatty Acids 



a. Acetaldehyde as the Two-Carbon Fragment Required for Fatty Acid 

 Synthesis. Acetaldehyde (CHs-CHO) was first assumed to be an inter- 

 mediate in the synthesis of fatty acids from glucose. Nencki^ discovered 

 that two molecules of acetaldehyde were formed from each molecule of 

 glucose when sugar was fermented by yeast; he further reported that these 

 acetaldehyde molecules condensed in an alkalhie medium to give aldol 

 (CH3-CHOH-CH2-CHO). It was suggested that this compound might 

 be converted to butyric acid. This theory was further expanded by Magnus- 

 Levy^ and by Raper^ to explain the formation of long-chain acids as a re- 



1 H. S. Raper, J. Chem. Soc, 91, 1831-1838 (1907). 



2K. Bloch, Physiol. Revs., 27, 574-620 (1947). 



3 K. Bloch, Cold Spring Harbor Symposia Quant. Biol, 13, 29-34 (1948). 



* A. Kleinzeller, Advances in Enzymol, 8, 299-341 (1948). 



^ G. Popjdk, Fat Synthesis from Small Molecules, in R. T. Williams, Lipid Metabolism, 

 Biochem. Soc. Sj-mposia, No. 9, Cambridge Univ. Press, 37-51 (1952). 



* S. J. FoUey, Aspects of Fat Metabolism in the Ruminant, with Special Reference to the 

 Biosynthesis of Milk Fat, in R. T. Williams, Lipid Metabolism, Biochem. Soc. Symposia, 

 No. 9, Cambridge Univ. Press, 52-65 (1952). 



' C. Medes, M. A. Spirtes, and S. Weinhouse, J. Biol. Chem., 205, 401-408 (1953). 



8 M. Nencki, /. prakt. Chem. [2], 17, 105-124 (1878). 



3 A. Magnus-Levy, Arch. Anat. Physiol., Physiol. AM., 1902, 365-368. 



