Problems in Lipide Metabolism 



SAMUEL GURIN 



It is now half a century since Knoop x fed w-phenyl-substituted 

 aliphatic acids to dogs and isolated as excretory products either hip- 

 puric or phenaceturic acids, depending upon the number of aliphatic 

 carbon atoms in the administered acids. Ever since that time, and 

 with a great crescendo during the past decade, biochemists have sought 

 for a definitive explanation of the way in which fatty acids are oxidized 

 by living tissue. The problem could undoubtedly have been epitomized 

 by a certain well-known writer of detective stories as "The Case of 

 the Mysterious Two-Carbon Fragment." Had an imaginary writer 

 begun his story in 1904, it is only now that he would be able to write 

 his concluding chapter. 



Evidence that 2-carbon fragments arise during the biological oxida- 

 tion of fatty acids has come from so many sources and in such over- 

 whelming volume that there is very little point in belaboring the matter. 

 The isolation of acetyl coenzyme A by Lynen and his group in 1951 - 

 brought the field to a new turning point and settled conclusively the 

 nature of the active 2-carbon fragment. It is fitting to pay tribute 

 to the fine work of Lipmann, Nachmansohn, and others who uncovered 

 the role of coenzyme A and ATP in the activation of acetate. 



That fatty acids must have their carboxyl groups free prior to their 

 utilization was strongly indicated by Lehninger's work 3 with mito- 

 chondria. Lynen's 4 hypothesis, that long-chain acyl CoA derivatives 

 are produced before fatty acids can be oxidized, fitted beautifully with 

 such a notion. 



It should of course not be forgotten that the demonstration by Drys- 

 dale and Lardy 5 and Mahler 6 that oxidation of fatty acids could be 

 achieved in mitochondrial extracts paved the way for the spectacular 

 advances in this field. With an appropriate electron acceptor it was 

 clearly established that fatty acids could be activated, oxidized, and 



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