Cholesterol isovalerate

The pyrethroid insecticide fenvalerate, (a-cyano-3-phenoxybenzyl-2-(4-chlorophenyl)isovalerate, contains two centers of chirality in its structure (designated as the 2 and a positions Fig. 19) and therefore four stereoisomers, two pairs of enantiomers are possible. Initial evaluation of the mixture, by addition to the diet of a number of species, resulted in granulomatous changes in the liver, lymph nodes, and spleen. Separation and evaluation of the individual stereoisomers indicated that the toxidty was associated with one of the four, the 2i ,a5-stereoisomer, and subsequent metabolic studies found the cause to be associated with the formation and disposition of a cholesterol ester of (i )-2-(4-chlorophenyl)isovalerate (Fig. 19). A metabolic transformation shown to be stereospedfic in mice, only the 2i ,a5-stereoisomer yielding the ester both in vitro and in vivo [159]. 

Figure 19 Fenvalerate and the structure of (/ )-2-(4-chlorophenyl)isovaleric acid cholesterol ester.

A clue to the catabolism of leucine was secured from the observation of Bloch that administration of deutero leucine or isovalerate yielded a high concentration of deuterium in cholesterol and in the acetyl group of N-acetyl phenylaminobutyric acid. This demonstrated that a 2-carbon unit is a normal breakdown product of leucine and of isovaleric acid. The equivalence obtained with respect to the formation of acetate from leucine and isovaleric acid offered support to the hypothesis that conversion to... 

It can be seen that this hypothetical Cs 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 Cs 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 COj to form acetoacetate. 

Both isotopes in fatty acids. Iso- (212) propyl group more efficient source of carbons for cholesterol than acetate or carboxyl fragment of isovalerate... 

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