2-Oxo-3-methyl-n-valerate

Fig. 10.4 Chromatogram of organic acids extracted from the same urine of the patient illustrated in Fig. 10.3, separated as their O-n-butyloxime and trimethylsilyl derivatives under the conditions described in the legend to Fig. 10.2. Peak identifications are 1, lactate 2, glycollate 3, unidentified 4, 2-hydroxy-n-butyrate plus 3-hydroxy-propionate 5, sulphate 6, 3-hydroxybutyrate and 3-hydroxyisobutyrate 7, 2-hydroxyisovalerate 8, 3-hydroxyisovalerate 10, 2-hydroxyisocaproate 11,2-hydroxy-3-methyl-n-valerate 12, phosphate 13,2-oxoisovalerate (peak 1) 14,2-oxoisovalerate (peak 2) 15, 2-oxo-3-methyl-/i-valerate (peak 1) 16, 2-oxo-3-methyl-n-valerate (peak 2) 17, 2-oxoisocaproate 18, citrate 19, 4-hydroxyphenyl-lactate 20, n-tetracosane (standard) 21, n-hexacosane (standard). The separation of O-n-butyloxime-TMS derivatives of the keto acids from the TMS-hydroxy acids and other components is apparent (compare with Fig. 10.3). Note the apparent loss of 4-hydroxyphenylpyruvate. (The horizontal axis represents the time elapsed in minutes from sample injection.)...

Fig. 10.5 Mass spectra of the ethoxime-trimethylsilyl derivatives of (a) 2-oxoisovaleric, (b) 2-oxo-3-methyl-n-valeric (peak 1), (c) 2-oxo-3-methyl-/i-valeric (peak 2) and (d) 2-oxoisocaproic acids and the trimethylsilyl derivatives of (e) 2-hydroxyisovaleric, (f) 2-hydroxy-3-methyl-rt-valeric and (g) 2-hydroxyisocaproic acids.

Fig. 10.3 Chromatogram of organic acids extracted from the urine of an untreated patient with branched-chain keto aciduria (maple syrup urine disease), extracted and separated as described in the legend to Fig. 10.2. The chromatogram illustrates the overlapping peaks in the regions occupied by 3-hydroxybutyric, 2-hydroxyisovaleric and 2-oxoisovaleric acids (peak 1) and 2-oxo-3-methyl-valeric, 2-hydroxyisocaprioic and 2-oxoisocaproic acids (peak 2) and phosphate (peak 3). Other peaks of interest are (4) citric, (5) 4-hydroxyphenyl-lactic, (6) 4-hydroxyphenylpyruvic, (7) n-tetracosane (standard) and (8) -hexacosane (standard). (Compare with Fig. 10.4.)...

Hydroxy-n-valeric acid is perhaps the most frequently observed urinary metabolite after methylcitrate and 3-hydroxypropionate, and 3-oxo-/r-valeric acid may also occur during severe ketosis. During non-ketotic periods, when propionyl-CoA accumulation still occurs, two molecules of this substrate may condense via the action of a j3-ketothiolase to form 2-methyl-3-oxovaleryl-CoA, resulting ultimately in the excretion of 2-methyl-3-hydroxyvaleric and 2-methyl-3-oxovaleric acids in the urine (Lehnert et ai, 1978 Truscott et al., 1979). The occurrence of these keto acids explains the presence of long-chain ketones in the urine, formed by decarboxylation in an analogous manner to the formation of acetone from acetoacetate (Fig. 11.6). 

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