Dihydroxy methyl valeric acid

Tavormina, P. a., and M. H. Gibbs The metabolism of p, y-dihydroxy-j5-methyl valeric acid by liver homogenates. J. Amer. chem. Soc. 78, 6210 (1956). 

Following the ketol condensation to yield a-acetolactate and a-aceto-a-hydroxybutyrate the question arises as to whether the pinacol rearrangement occurs first to form a-keto-jS-hydroxyisovaleric acid and a-keto-i9-hydroxy- 8-methylvaleric acid (Fig. 7, III), or whether there is prior reduction. The evidence favoring pinacol rearrangement followed by reduction of the a-keto- 3-hydroxy acids is that enzymes have been found in Neurospora and E. coli which catalyze the reduction of synthetically prepared a-keto-(8-hydroxyisovaleric acid and a-keto-j8-hydroxy-/3-methyl-valeric acid to the corresponding a,/8-dihydroxy acids (166, 167). 

The subsequent conversion of 2-oxobutyrate to isoleucine involves four enzymes. The same enzymes are considered to participate in the biosynthesis of valine (Fig. 4). Thus, 2-oxobutyrate and its three carbon analogue, pyruvate, would be alternate substrates of acetohydroxyacid synthase. This parallel reaction sequence (Fig. 4) is initiated by the addition of a two-carbon fragment to the 2-carbon of the 2-oxobutyrate or pyruvate. The resultant acetohydroxyacids are reduced with concomitant isomerization to form dihydroxy acids. Dehydration yields oxoacids which are then transaminated to synthesize isoleucine and valine. Both 2-oxoisovalerate and 2-oxo-3-methyl-valerate have been identified as components of plant extracts (Kretovich and Gejko, 1964). 

The oil has been exhaustively examined by E. R. Miller, who finds the following substances present therein d-o-pinene, i -a-pinene, p-cymene, one or two unidentified terpenes, butyric aldehyde, iso-valeric aldehyde, a third aldehyde, possibly piperonal, carvacrol, thymoquinone, hydro-thymoquinone, dihydroxy-thymoquinone, dihydrocuminic alcohol, an unidentified alcohol, acetic acid, butyric acid, valeric acid, caproic acid, basic substances, and (in the aqueous distillate) acetone, formaldehyde, methyl alcohol, formic acid, and acetic acid. 

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