32 Essays in Biochemistry 



of maleylacetoacetate to fumarylacetoacetate which Knox has de- 

 scribed. 18 



It is particularly relevant to the present discussion that squalene 

 has been shown to possess the all trans configuration. 19 The present 

 hypothesis would therefore anticipate trans-methylglutaconate as a 

 precursor of the triterpene and of the steroid derived from it. Two 

 observations have been made which are consistent with the role as- 

 signed to the methylglutaconic acids. Rabinowitz and Gurin 20 have 

 shown that hydroxymethylglutarate is dehydrated by liver prepara- 

 tions, and they state that ^?w?s-methylglutaconic acid is the product. 

 Second, the cis form of the same acid has been tested in our laboratory 

 as a cholesterol precursor and found to be inactive. Neither of these 

 two observations are conclusive by themselves, but, taken together 

 with the behavior of DMA as discussed earlier, they strengthen the 

 case for a pivotal role of the cis and trans isomers of the methyl- 

 glutaconic acids in terpene and steroid biogenesis. 



Though the main object of this essay has been to indicate current 

 lines of thinking and investigation in a selected area of terpene and 

 steroid biogenesis, it has been the intent to look also briefly at the 

 origin of the branched-chain amino acids. Comparison of the two 

 areas of biosynthesis raises the interesting point why higher animals 

 can synthesize one type of carbon chain, but not another closely related 

 one. 



Acetyl units are not the precursors of the branched portions of valine 

 and leucine. 21 Instead, it appears that the carbon skeletons of these 

 amino acids are formed from two molecules of pyruvate by a mecha- 

 nism which may involve an acyloin condensation to acetolactate and 

 a subsequent pinacol rearrangement to an isovaleric acid derivative. 22 ' 23 

 There is also evidence that one of the immediate valine precursors, 

 after condensation with an acetyl unit and decarboxylation, furnishes 

 the carbon chain of leucine. 1 ' 4 It is of particular interest for the pur- 



oh on 



2CH 3 CO— COOH -> CH 3 C— COOH -^ (CH 3 ) 2 C— CO— COOH 



Valine precursor 



CO 



I 



CH 3 

 OH 



(CH 3 ) 2 C— CO— COOH + CH3COOH - ^> Leucine precursor 



