BIOSYNTHESIS 237 



acetate. In the case of the corticosteroids, experiment has shown that they 

 are formed from cholesterol molecules brought to the gland in the plasma. 

 The formation of cholesterol from acetate takes place through the inter- 

 mediate stage of acetoacetate, as has been shown in numerous experiments. 



An examination of the distribution in the cholesterol molecule of the 

 carbons from methyl and those from the carboxyl of acetate, does not 

 immediately suggest the mode of synthesis. But it does limit the 

 possibilities. 



The addition of a further acetic acid residue to the keto-group of aceto- 

 acetic acid, followed by a decarboxylation, yields a Cs branched chain 

 (three carbons arising from methyl groups and two from the carboxyl of 

 acetate) . 



It can be seen that this hypothetical C5 compound can be superimposed, 

 with respect to the origin of the carbon atoms, on the terminal part of the 

 side chain of the cholesterol molecule (Fig. 61). If we now consider the 

 distribution in the ring, we see that the latter can also be conceived of as a 

 polymer of the same C5 chain. It has however been objected that this makes 

 isovaleric acid appear to be a possible precursor of cholesterol. In reality, 

 this happens only by way of acetoacetate. Isovaleric acid (and also leucine) 

 gives an isopropyl residue which combines with CO2 to form acetoacetate. 



What is the nature of the substance with the C5 chain? Let us recall the 

 synthesis of isoprene, the starting point for carotenoids and terpenes, from 

 acetate; we see that this synthesis leads to the C5 arrangement we are 

 seeking. Arguments have been advanced previously to implicate the iso- 

 prenoid, squalene, in the biosynthesis of steroids. Squalene is not limited 

 solely to the tissues of the selachians. Traces have been found everywhere 

 in animal tissues where it has been sought. When we consider that isoprene 

 units, as we have already indicated, are derived from acetate, we may 

 represent squalene as in Fig. 62 and compare it with Fig. 61. 



