KONRAD BLOCK 



j3-ethyl derivatives, respectively, of a-aminobutyric acid. Ta- 

 tum and Adelberg, working with Neiirospora mutants, have ob- 

 tained evidence that a precursor common to both amino acids is 

 formed by a "methyl" condensation of acetate with a 4-carbon 

 hydroxy-keto acid (22). Their results point to a 6-carbon 

 dicarboxylic acid as a common intermediate which can be 

 metabolized by either one of two pathways: (7) the "acetate" 

 carboxyl is reduced and the reduction product converted fur- 

 ther to isoleucine; (2) the same carboxyl group is removed by 

 decarboxylation, leaving the carbon skeleton of valine (Figure 7). 

 By analogy one may visualize a branching of the isooctenyl 

 side chain of lanosterol through attachment of an acetate unit 

 to G24, affording an intermediate with 32 carbon atoms. Either 

 one of two pathways may then be followed : ( 7) reduction of the 

 branched portion to an ethyl group to yield the C32 precursor of 

 the plant sterols, or (2) decarboxylation to a hypothetical ergos- 

 terol precursor containing 31 carbon atoms. Finally, removal 

 of the methyl groups at 044. and G14 and introduction of the 

 appropriate double bonds will afford either ergosterol or the C29 

 sterols (Figure 7). 



What is proposed here is admittedly highly speculative, and 

 one would wish for some evidence at least capable of supporting 

 the proposed mechanism for the biogenesis of plant and myco- 

 sterols. One single finding may be cited that is relevant, al- 

 though negative in nature. According to Hanahan and Wakil 

 (12), C28, the branched carbon of ergosterol, is not derived from a 

 carboxyl group of acetate, as one would expect from the scheme 

 postulated in Figure 7. 



It has been the object of this discussion to emphasize how 

 critically the progress of biochemical research, in some areas at 

 least, depends upon the discovery and identification of novel 

 structures in natural sources. Had it not been for the isolation 

 of squalene from shark liver or of lanosterol from wool fat, the 

 task of recognizing intermediates in the complex transformation 

 of acetic acid to cholesterol would have been infinitely more 

 difficult. Similarly, with the discovery of the polyporenic acids, 



490 



