INTERCONVERSIONS OP POLYUNSATURATED FATTY ACIDS 811 



(6) Mechanism of the Conversion. The reactions involved in the change 

 of one unsaturated acid to another have been largely a matter of conjec- 

 ture. Reiser'^^ suggested that "fragments of the ingested acids containing 

 the double bonds might combine to form the more highly unsaturated mem- 

 bers of the series." Thomasson'^ is in agreement Avith Greenberg/"'* 

 who suggests that two molecules of linoleate give rise to one arachidonic 

 acid molecule. Sinclair '^^ was likewise convinced of the synthesis of ara- 

 chidonic acid from linoleic acid, "despite the improbability of a change 

 involving the addition of two carbon atoms and desaturation at the 5:G 

 and 8:9 positions." Although the mechanism of these changes is not 

 entirely understood, Mead et aZ.'"'* demonstrated it in the intact animal. 

 These workers found that acetate was incorporated into arachidonic acid 

 by addition to an exogenous (unlabeled) Cis compound. The nature of 

 this compound was demonstrated by the fact that the carboxy group of 

 linoleic acid appeared as the third carbon in the arachidonic acid, as demon- 

 strated by Steinberg and associates.'*'^ Lack of activity beyond the third 

 carbon demonstrated that linoleate or an intact Cis derivative was indeed 

 the precursor of arachidonic acid. As was expected, acetate derived by 

 degradation of the active linoleate appeared in the carboxyl group of the 

 arachidonate. Following the feeding of carboxyl-labeled linolenate to 

 rats, no appreciable amount of activity was found in the linoleate isolated 

 from the rats, as pointed out by Mead, Steinberg ef al.^^^-"° The activity 

 did appear in the arachidic acid derived from the ether-insoluble poly- 

 bromides, however, predominantly in the first and third carbons. This 

 demonstrated that linolenate was incorporated into the twenty-carbon poly- 

 unsaturated acids, but there was some doubt that arachidonic acid was 

 involved, because of the lack of activity of the linoleic acid. Alkali-isom- 

 erization confirmed previous e\'idence that pentaene and hexaene were 

 increased following linolenate feeding, and chromatography of the poly- 

 unsaturated acids from the experiment re\'ealed that most of the activity 

 was in fractions other than that containing the arachidonic acid. These 

 data suggest that linoleate and linolenate are the progenitors of two families 

 of polyunsaturated acids formed by the addition of double bonds toward 

 the carboxy end (in the 1 :4-relationship) continued to a closest approach 



i"R. Reiser, Arch. Biochem. Biophrjs., S3, 113-120 (1951). 



!<« J. F. Mead, G. Steinberg, and D. R. Howton, /. Biol. Chem., 205, 683-689 (1953). 



1" G. Steinberg, W. H. Slaton, Jr., D. R. Howton, and J. F. Mead, J. Biol. Chem., 220, 

 257-264 (1956). 



1™ J. F. Mead, G. Steinberg, W. H. Slaton, Jr., and D. R. Howton, Univ. California 

 (Los Angeles), Atomic Energy Project, Report No. 360, Feb. 15, 1956; Federation Proc, 15, 

 313-314(1956). 



