Biosynthesis of Branched-Chain Compounds 31 



CH 2 COOH COOH 



I I 



CH 3 C=CH— COR + H 2 C— C=CH— COR -> 



I 

 CH 3 



CH 2 COOH COOH 



CH 3 C=CH— CO— CH— C=CH— COR ^> 



I 



CH 3 

 CH 3 



\ 



C=CH— CO— CH 2 C=CH— ( !OR 



/ I 



CH 3 CH 3 



more favorable for reaction in a Claisen-type condensation. In this 

 event the same Cio unit will be formed, but decarboxylation would 

 follow or at least not precede the condensation step. It will be noted 

 that the carbon atoms removed by the decarboxylation step will again 

 be the original carboxyl groups of DMA. This second mechanism 

 therefore accounts equally well for the experimental data obtained 

 with 1-C 14 DMA or isovaleric acid, but cyclic regeneration of a 5- 

 carbon compound would not be obligatory. 



The existence of methylglutaconic acid in two stereoisomeric forms 

 is the second structural feature of particular interest for polyisoprenoid 

 synthesis. The natural acyclic terpenes occur both in the cis (e.g., 

 nerol and rubber) and trans forms (geraniol, gutta-percha, and squal- 

 ene I , and it is pertinent to ask at what stage of the overall synthetic 

 process the geometric configuration of the respective products becomes 

 established. If DMA were the condensing unit, the stereospecific step 

 would follow the condensation reaction. On the other hand, the cis 

 and trans .isomers of methylglutaconic acid would constitute precursors 

 which already possess the configuration of the end product. Present 

 biochemical knowledge is too scarce to predict the nature of the stereo- 

 specific steps, although at least one prototype exists. Dehydration of 

 hydroxy acids (malic, citric, and /?-hydroxybutyric acids) is a well- 

 established enzymatic reaction which affords geometric isomers, and 

 hence the formation of methylglutaconic acid by elimination of water 

 from hydroxymethylglutarate would not be without precedent. Which 

 one of the two isomers will be formed cannot be predicted, nor can the 

 possibility be ignored that the cis and trans forms are converted into 

 each other enzymatically by a reaction analogous to the isomerization 



