Isovaleric acid decarboxylation

Leucine is a branched chain-amino acid that is essential or required in the diet. Mitochondrial catabolism of excess leucine occurs by the pathway shown in Figure 20-3. The initial transamination step (removal of the amino group) is followed by a decarboxylation reaction to produce isovaleric acid. It is this decarboxylation of the a-keto analogs of the three... 

Volatile fatty acids p resent in wine may derive from the anabolism of lipids, resulting in compounds with even number of carbon atoms, by oxidative decarboxylation of a-keto acids or by the oxidation of aldehydes. Volatile fatty acids synthesised from a-keto acids are mainly propanoic add, 2-methyl-l-propanoic acid (isobutyric acid), 2-methyl-l-butanoic acid, 3-methyl-l-butanoic acid (isovaleric acid 3-methylbutyric add) and phenylacetic add. From lipid metabolism, the following fatty acids are reported butanoic add (butyric), hexanoic acid (caproic), odanoic acid (caprylic) and decanoic add (capric) (Dubois, 1994). Although fatty adds are charaderized by unpleasant notes (Table 1), only few compounds of this family attain its perception threshold. However, their flavour is essential to the aromatic equilibrium of wines (Etievant, 1991). 

The question arises as to whether acetone is a primary product of the oxidation of isovalerate or is formed secondarily by decarboxylation of acetoacetate. The experimental results of Zabin and Bloch are in accord with a reaction mechanism in which isovaleric acid is oxidized initially at the carbon 2-position to yield a 3-carbon and a 2-carbon fragment. This conclusion is based on the high absolute C concentrations found in the methyl carbons of acetone and also in comparison to that in the methyl or methylene carbons of acetoacetate. Secondly, the C C ratios were significantly greater in the acetone fractions than in the corresponding carbon atoms of acetoacetate. This finding can be explained only if acetone is formed directly from isovaleric acid, but is at variance with the assumption that acetone arose exclusively by decarboxylation of acetoacetate. The authors also point out that it is possible that the postulated 3-carbon intermediate is not acetone, but that acetone is formed in a side reaction from a more labile 3-carbon precursor. 

The three branched chain amino acids are normally metabolized as shown in Figure 6.2. Each amino acid is converted to the corresponding Of-keto acid by a transaminase specific for that amino acid. A solitary case of valinaemia is known, caused by lack of valine transaminase [76] the patient is mentally retarded. The three a-keto acids are decarboxylated by two (or possibly three) enzyme systems, one specific for a-keto-isovaleric acid, the other acting on a-keto-isocaproic and Q -keto-j3-methylvaleric acids [77, 78]. The reaction is complex, proceeding in three distinct steps [78] and requiring coenzyme A, thiamine pyrophosphate, lipoic acid and NAD. The end products are the co-enzyme A thio-esters of the branched chain fatty acids. 

The oxidation of heptane and hexane by a strain of Pseudomonas aeruginosa was found to occur by oxidative attack of one terminal carbon atom, yielding the corresponding fatty acids, which were further degraded by j8-oxidation (Heringa et al., 1961). Evidence for a decarboxylation of the fatty acids could not be found. Two pathways of oxidation of 2-methylhexane were found. The main attack occurs in the C-6 yielding 5-methylhexanoic acid and, via /3-oxidation, isovaleric acid. The second, minor pathway involves attack of the other end of the hydrocarbon molecule, namely, the C-1, yielding 2-methylhexanoic acid (Thijsse and van der Linden, 1961). 

Mutation of the dihydrolipoate reductase component impairs decarboxylation of branched-chain a-keto acids, of pyruvate, and of a-ketoglutarate. In intermittent branched-chain ketonuria, the a-keto acid decarboxylase retains some activity, and symptoms occur later in life. The impaired enzyme in isovaleric acidemia is isovaleryl-CoA dehydrogenase (reaction 3, Figure 30-19). Vomiting, acidosis, and coma follow ingestion of excess protein. Accumulated... 

Fujii et al. (1988) reported a mechanism of isobutene formation by the yeast Rhodotorula minuta in a culture medium that contained branched-chain carboxylic or amino acids. It was suggested that the pathway leads over isovalerate that is decarboxylated to isobutene. 

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