Problems in Lipide Metabolism 139 



CoA which occurs readily in liver involves a condensation with aceto- 

 acetate or acetoacetyl CoA yielding eventually /Miydroxy-£-methyl- 

 glutaconic acid.--' This substance readily yields squalene and cho- 

 lesterol in aqueous liver extracts. 23 Although this particular segment 

 of the field presents many uncertainties which need clarification, it is 

 apparent again that an overproduction of acetyl CoA (and aceto- 

 acetate?) provides a situation which is favorable for increased bio- 

 synthesis of cholesterol. That labeled acetoacetate can be incorporated 

 into cholesterol by liver slices has been well established. 24 



Our rapidly increasing knowledge of the chemical pathways involved 

 in the oxidation and biosynthesis of fat has shown us where the railroad 

 tracks go and something about the location of the switches in this 

 complicated railway system. Turnover studies tell us something about 

 the volume of traffic. We know also that, in certain situations, some 

 switches are open and others are closed. The manner in which hor- 

 monal and physiological regulation influence these biochemical path- 

 ways will challenge the best efforts of biochemists and biologists for 

 many years to come. 



It is manifestly impossible to do justice to the many outstanding 

 contributions that have been made in this difficult field. Many have 

 not been touched upon. Such problems as the nature of the linkages 

 in complexes of protein and lipide, the mode of synthesis of the long- 

 chain polyethenoid acids, the biosynthesis of carotenoids and various 

 terpenoid substances will occupy the attention of biochemists for many 

 years. An attempt has been made here only to highlight a few prob- 

 lems that happen to interest the author. Excellent review articles 

 have been published by Lehninger, 10 Green, 10 and Chaikoff. 16 



Current developments in enzymology have depended very heavily 

 upon information obtained with stable and radioactive isotopes. The 

 author was privileged to witness some of the early applications of these 

 research techniques to the study of intermediary metabolism. It is 

 therefore a source of gratification that, from these beginnings, there 

 has developed a renaissance in intermediary metabolism which is now 

 in full tide. 



References 



1. F. Knoop, Beitr. chem. physiol. Pathol, 6, 150 (1904). 



2. F. Lynen and E. Reichert, Angew. Chem., 63, 47 (1951). 



3. A. L. Lehninger, ./. Biol. Chan., 154, 309 (1944); 157, 363 (1945); Wl, 413, 

 437 (1945); 162, 333 (1946). 



4. F. Lynen, E. Reichert, and L. Rueff, Ann. Chem., 57/,, 1 (1951). 



