Ketols biosynthesis

Most known thiamin diphosphate-dependent reactions (Table 14-2) can be derived from the five halfreactions, a through e, shown in Fig. 14-3. Each half-reaction is an a cleavage which leads to a thiamin- bound enamine (center. Fig. 14-3) The decarboxylation of an a-oxo acid to an aldehyde is represented by step h followed by fl in reverse. The most studied enzyme catalyzing a reaction of this type is yeast pyruvate decarboxylase, an enzyme essential to alcoholic fermentation (Fig. 10-3). There are two 250-kDa isoenzyme forms, one an tetramer and one with an (aP)2 quaternary structure. The isolation of a-hydroxyethylthiamin diphosphate from reaction mixtures of this enzyme with pyruvate provided important verification of the mechanisms of Eqs. 14-14,14-15. Other decarboxylases produce aldehydes in specialized metabolic pathways indolepyruvate decarboxylase in the biosynthesis of the plant hormone indole-3-acetate and ben-zoylformate decarboxylase in the mandelate pathway of bacterial metabolism (Chapter 25). Formation of a-ketols from a-oxo acids also starts with step h of Fig. 14-3 but is followed by condensation with another carbonyl compound in step c, in reverse. An example is decarboxylation of pyruvate and condensation of the resulting active acetaldehyde with a second pyruvate molecule to give l -a-acetolactate, a reaction catalyzed by acetohydroxy acid synthase (acetolactate synthase). Acetolactate is the precursor to valine and leucine. A similar ketol condensation, which is catalyzed by the same S5mthase, is... 

Significant diversity exists among the CoA biosynthetic pathways of various organisms. For example, the discussions of the CoA biosynthesis enzymes above highlighted the existence in some cases of two or more distinct nonhomologous proteins that all exhibit the same activity. The transformation of ketopantoic acid 4 to pantoic acid 5 in the biosynthesis of pantothenic acid can also be catalyzed by one of the two proteins a strict KPR enzyme (the gene product EC 1.1.1.169) or the ketol-acid reductoisomerase (tfoCgene product EC... 

The conclusion was reached that the biosynthetic route was by way of a two-carbon insertion into 2-oxo-3-hydroxy-3-methylbutyric acid (CLXXIV). Taken in conjunction with the established bios3uithesis of valine (CLXXV) from pyruvic acid by way of acetyllactic acid (CLXXVI) and the ketol rearrangement to CLXXIV the biosynthesis of echimidinic acid may be formulated as in Chart VI. 

Schloss, J. V, Aulabaugh, A. Acetolac-tate Synthase and Ketol-Add Reduc-toisomerase A Search for Reason and a Reason for Search, in Biosynthesis of Branched Chain Amino Acids, Barak,... 

The last route is important for the formation of jasmonic acid. The action of allene oxide synthase on 13-hydroperoxy linolenic acid initially results in the generation of 12,13-epoxy-octadecatrienoic acid. This unstable epoxide is either chemically hydrolyzed to a- and y-ketols and racemic 12-oxo-phytodienoic acid or, in the presence of allene oxide cyclase (AOC), is further converted to enantiomeric pure 12-oxo-PDA [7]. The ring double bond of PDA is then reduced in a NADPH dependent reaction by 12-oxo-PDA reductase and after shortening of the side chain containing the carboxy group by 3 rounds of fi>-oxidation, the biosynthesis of jasmonic acid is completed. 

Support that a-aceto-a-hydroxybutyrate is on the pathway of isoleucine biosynthesis was obtained by Watanabe et al, (166), who prepared this ketol condensation product of a-ketobutyric acid and acetaldehyde and demonstrated that it was converted to L-isoleucine by cell-free extracts of baker s yeast. 

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