2-Hydroxyisocaproic acid

Fig. 3-84. Separation of various monocarboxylic acids at an anion exchanger IonPac AS6 (CarboPac). - Eluent 0.0017 mol/L NaHCOj + 0.0018 mol/L Na2C03 flow rate 1 mL/min detection suppressed conductivity injection 50 pL solute concentrations 3 ppm fluoride (1), 40 ppm acetic acid (2), 20 ppm glycolic acid (3), 10 ppm a-hydroxyisocaproic acid (4), 20 ppm formic acid (5), oxamic acid (6), methanesulfonic acid (7), amidosulfonic acid (8), and a-ketoisocaproic acid (9).

Fukuda and coworkers have described one of the first applications of the enantioselective hydrolysis of nitriles (Scheme 12.1-6). Using a whole cell biocatalyst optically pure a-hydroxy acids (L-a-hydroxyisovaleric acid and L-a-hydroxyisocaproic acid) have been prepared from the racemates of the corresponding a-hydroxyni-... 

Fig. 3.22. GC separation of keto and hydroxy acids from the urine of a patient with maple syrup urine disease. Top chromatogram, the patient before dietary treatment middle chromatogram, the same patient after two days on a diet bottom chromatogram, a mixture of reference compounds. Peaks 1, lactic acid 2, 2-hydroxyisobutyric acid 3, 2-hydroxybutyric acid 4, pyruvic acid 5, 3-hydroxyisobutyric acid 6, 3-hydroxybutyric acid 7, 2-hydroxyisovaleric acid 8, 2-ketobutyric acid 9, malonic acid (internal standard) 10, 2-methyl-3-hydroxybutyric acid 11, 2-hydroxy-n-valeric acid 12. methylmalonic acid 13, 3-hydroxyisovaleric acid 14a and b, 2-ketoisovaleric acid IS, acetoacetic add 16, 2-hydroxyisocaproic acid 17, 2-hydroxy-3-methylvaleric acid 18a, L-2-keto-3-methylvaleric add 18b, D-2-keto-3-methyl-valeric acid 19, 2-ketoisocaproic acid. Reproduced from [386],...

L-Leucine is derived from L-valine by the x-keto acid elongation system, i.e., via x-ketoisovaleric acid and -carboxy-j8-hydroxyisocaproic acid as outlined in Fig. 199. The transformation of ot-ketoisovaleric acid to (X-ketoisocaproic acid closely resembles the conversion of oxaloacetic acid to (X-ketoglutaric acid in the tricarboxylic acid cycle (D 5). x-Ketbacid elongation systems also participate in the formation of L-lysine via the x-aminoadipic acid pathway (D 18) and in the biosynthesis of a number of secondary amino acids which are precursors of gluco-sinolates (D 9.4). 

L. Lactis (84 strains) AA converting activity (cell extracts from cells grown in 2 media) Activity of branched chain aminotransferase (BcaT), alpha-hydroxyisocaproic acid dehydrogenase (HicDH), and esterase individual strains showed va-y diverse regulatory responses, with the activities in the 2 media in general poorly correlated (Bachmann et al. 2009)... 

D-HADH and L-HAOX assay. The enzymatic activities were estimated following Schreiner and Jones (1988) using D-lactate as substrate for D-HADH, and glycolic acid and L-2-hydroxyisocaproic acid for L-HAOX-A and B isozymes, respectively (Duley and Holmes, 1976). 

The results indicate that Caco-2 cells showed higher D-HADH (3.38 0.63 mU/pg protein, n=6, P<0.05) than L-HAOX activities. In the case of L-HAOX, the data reveal a higher capacity to convert glycolic acid than L-2-hydroxyisocaproic acid to KMB (0.28 0.04 vs. 0.12 0.01 mU/pg protein, n=4 cultures, P<0.05), thus suggesting that, although both L-HAOX-A and B isozymes are present, the isozyme A is more active. As for KMB transamination, the results indicate that all the amino acids tested (L-Leu, L-Val, L-Ala, L-Phe, L-Pro, L-Asn, L-Gln, L-Ser, L-Tyr, L-Asp, L-Glu,... 

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.

Position of 2-hydroxy-3-methyl-n-valeric and 2-hydroxyisocaproic acids. (Redrawn with modifications from Langenback etaly 1979)... 

Enzyme-catalyzed syntheses of enantiomeric pure hydroxy acids use lactate dehydrogenases (LDH E.C. 1.1.1.27) or hydroxyisocaproate dehydrogenases (HicDH). Both kinds of enzymes are available as D- or L-specific catalysts. L-specific [5, 6] LDHs as well as D-specific [7-10] LDHs favorably catalyze the reduction of pyruvate, HicDHs (and mandelate dehydrogenase, too) convert keto acids with longer aliphatic or aromatic side chains. These enzymes can be isolated from Lactobacillus strains [11-14]. 

There are two lactate dehydrogenases (LdHs) with different stereospecificities that have been very useful for the preparation of chiral 2-hydroxy acids.33 4 L-LdH (E.C. 1.1.1.27) and D-LdH (E.C. 1.1.1.28) are obtained from various microbial sources (Table 19.1). Along with hydroxyisocaproate... 

Commercially available C. boidinii-FDH was used to recycle the NADH cofactor in stereospecific reductions by (/ )-2-hydroxyisocaproate dehydrogenase from L. casei [174]. Enantiomerically pure (R)-2-hydroxy-4-methylpentanoic acid was obtained with 88% yield. The broad substrate specificity of this enzyme enables the synthesis of a broad range of enantiomerically pure ot-hydroxy acids with aliphatic or aromatic side chains. 

Mandelic acid Benzoylformic acid Hydroxyisocaproate dehydrogenase... 

Little is known about the metabolism of branched-chain amino acids in parasites. Addition of leucine to Trichomonas vaginalis results in the production and release of a-hydroxyisocaproate synthesized via the corresponding keto acid, a-ketoisocaproate... 

DL-phenyllactic acid + NH D- and L-hydroxyisocaproate dehydrogenase + Phe dehydrogenase Eactobacillus casei ... 

Hummel W, Schiitte H, Kula MR (1985) D-2-Hydroxyisocaproate dehydrogenase from Lactobacillus casei. A new enzyme suitable for stereospedfic reduction of 2-ketocarboxylic acids. Appl Microbiol Biotechnol 21 7-15... 

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