LIPIDS 161 



heads: (1) the origin of the isoprene skeleton, (2) the mode of con- 

 densation of isoprene units to form the 40-carbon chain of the 

 carotenoids, and (3) the relation of the different carotenoids to one 

 another. 



On grounds of comparative biochemistry and especially from studies 

 on higher plants (304), the most likely route of synthesis of the iso- 

 prene skeleton involves the following steps (236, 346): 



1. Formation of acetoacetic acid from acetate and coenzyme A. 



2. Condensation of acetoacetate with acetyl-coenzyme A to form 

 ^-hydroxy, /3-methylglutaryl-coenzyme A. 



3. Conversion of /^-hydroxy, /?-methylglutaryl-coenzyme A to p- 

 methylcrotonyl-coenzyme A. This process involves more than one 

 reaction and includes a decarboxylation. 



The condensation of two 5-carbon units to yield a 10-carbon chain, 

 followed by successive reactions with new 5-carbon units, could in 

 principle yield the 40-carbon chain of the carotenoids (346). 



Evidence for the foregoing scheme in the fungi is somewhat limited, 

 but adequate to establish it as a working hypothesis. Caroteno- 

 genesis in fungi is stimulated by /?-methylcrotonaldehyde (237) and by 

 pantothenic acid and pantethine, which enter into the coenzyme A 

 molecule (249). The labeling of the ^-carotene of Mucor hiemalis 

 grown on C 14 -acetate is qualitatively consistent with the proposed 

 mechanism (247, 248, 248a). That fungi form carotenoids during 

 cultivation on acetate (463) cannot be urged as proof for the hypoth- 

 esis, although again the fact is consistent with it. 



The final set of problems is associated with the relationship of the 

 carotenoids to one another. From genetic data on higher plants, 

 Porter and Lincoln (427) proposed a unilinear sequence of formation 

 of the carotenoids by successive dehydrogenations, that is, that the 

 unsaturated hydrocarbons are derived from the saturated, as follows: 



Tetrahydrophytoene -> phytoene -» phytofluene -> ^-carotene -» 



neurosporene — > lycopene — » y-carotene — » 



/3-carotene — > a-carotene. 



Although this scheme fits the behavior of mutants of Chlorella vulgaris 

 (138), Rhodotorula rubra (89) and Neurospora crassa (264, 469), it 

 cannot be regarded as proved. Goodwin (232, 233) has argued, largely 

 on the basis of inhibitor studies, that the more saturated polyenes, 

 e.g., phytofluene, are formed by one pathway, the less saturated, e.g., 

 /3-carotene, by another, both from a common precursor. The effects 

 of added methylheptenone and /?-ionone have been interpreted as 



