30 Essays in Biochemistry 



counts as intermediates in terpene and steroid biogenesis. Decarbox- 

 ylation, by removal of the carboxyl group which was originally present, 

 would regenerate DMA with retention of four of the five original 

 carbon atoms. The molecule becomes reoriented, and the carboxyl 

 group which was newly introduced will now be linked to the opposite 

 end of the original molecule. If the cyclic regeneration of DMA 

 occurred at a sufficiently rapid rate, then not only would the original 

 carboxyl carbons be lost entirely but at the same time the isopropyl 

 carbons 4 and 4' would become equilibrated with carbon atom 2 (see 

 Fig. 3, reactions 2 to 6). In this event the labeling pattern in the 

 eventual product of isoprene synthesis, e.g., cholesterol, should not be 

 specific, i.e., it should be identical with that given by 2-C 14 -acetate. 

 This has actually been found to be the case with 4,4'-C 14 -isovaleric 

 acid. 



It should be emphasized perhaps that in the conversion of acetate 

 to terpenes and steroids, dimethylacrylic acid need not be a direct 

 intermediate; possibly it joins the main synthetic path merely by 

 virtue of its conversion to methylglutaconic acid, and normally this 

 dicarboxylic acid is formed chiefly from acetate and acetoacetate by 

 way of hydroxymethylglutarate. The obvious reason why the discus- 

 sion has nevertheless centered around dimethylacrylate is its superi- 

 ority over other branched-chain acids as a precursor of cholesterol. 



The arguments presented so far imply that DMA (or a coenzyme 

 derivative) is the monomeric unit which enters into the synthesis of 

 polyisoprenoid chains. This reaction would be analogous to the fi- 

 ketoacyl condensation which is the well-established mechanism for the 

 synthesis of the straight-chain aliphatic acids. One may question, 

 however, the likelihood that isopropylidene groups are sufficiently re- 



CH 3 



\ 



C=CH— COR 4- H 3 C— C=CH— COR -> 



/ I 



CH 3 CH 3 



CH 3 



\ 



C=CH— COCHoC=CH— COR 



/ "I 



CH 3 CH 3 



active to enter into a condensation of this type. By contrast the 

 methylglutaconic group possesses a methylene group which should be 



