io8 



INTERMEDIARY METABOLISM AND GROWTH 



(Kennedy, 1953). At the same time, the a-glycerol phosphate becomes labelled. Moreover, 

 a-glycerol phosphate-"? is itself incorporated into phosphatidic acid and mitochondrial 

 phospholipids. The mechanism of lecithin and phosphatidyl ethanolamine formation may 

 be a general one, applicable to the synthesis of serine phosphatides and acetal phosphatides. 

 Sphingomyelin, although not a glycerophosphatide, has a phosphoryl choline moiety like 

 that of lecithin and it is possible that CDP-choline may be a precursor of this portion of 

 the sphingomyelin molecule. 



Phosphoglycerol choline and phosphoglycerol ethanolamine also occur in aqueous 

 extracts of tissues. However, these compounds are probably degradation products rather 

 than precursors of phosphatidyl choline or ethanolamine (Dawson, 1955). 



G. Vitamin Biosynthesis 

 I. Cholesterol and vitamins A and D^^ 



Carotenoids are present in virtually all plants. It is probable that the carotenoids 

 are formed by the polymerization of an "isoprene-like precursor" compound. The 

 distribution of the carbon atoms in vitamin A conforms to that expected from the 

 polymerization of four isoprene units. The five carbon compound, [i-methyl- 

 crotonyl-CoA, is probably closely related to the "isoprene-like" precursor. This 

 compound is an intermediate in the catabolism of leucine and can also be formed 

 from acetyl-CoA and acetoacetic acid by animal tissues (Fig. 48). 



COOH 



HC— NHj 



I 



CH 



/\ 



H3C CH3 



Leucine 



COOH 



I 



c=o 



I 



CH, -COs 



C-S-CoA 



I 

 CH, 



2H' 



CH 



/\ 



HX CH. 



CoA 



a - Ketoi socaproate 



CH 



/\ 



H3C CH3 



Isovaleryl- 

 CoA 



O 



II 

 C-S-CoA 



I 

 CH 



C 



/\ 

 H3C CH3 



o 



II 



CH^C-S-CoA 



CH^— CO — CH„— COOH 



o 



II 



C-S-CoA 

 I 

 =- CH, -== 



I 



H,C-C-OH 

 I 

 CHj-COOH 



y6 - Hydroxy-fi - methyl- 

 gkJtaryl-CoA 



^-Methyl 

 crotonyl- CoA 



+ H2O 



O 

 II 

 C-S-CoA 



AMP^COz 

 -CO, 



CH. 



I ' 



HX— C-OH 

 ' I 

 CH3 



^~ Hydroxy- isovaleryl 

 CoA 



Fig. 48. Conversion of leucine and acetyl-CoA to P-methylcrotonyl-CoA. 



The synthesis of p-methyl-[li-OH-glutaric acid and ^-methyl crotonic acid from 

 acetate-^'*C or pyruvate- i-^'*C is catalyzed by rat liver enzymes (Rabinowitz and 

 Gurin, 1954; Rabinowitz, 1954). The ^-methyl crotonic acid is formed by the 

 dehydration of ^-hydroxy-isovaleric acid, a reaction catalyzed by the enzyme 

 crotonase (Stern et al., 1956a). Enzymes have been ptirified from heart tissue which 

 catalyze the formation of [3-methyl-p-hydroxyglutaryl-CoA from ^'*CO-, (Bach- 

 hawat^/fl/., 1956a). A high energy adenyl-C02 compound is apparently an inter- 



