3- Hydroxyisobutyric

J Hasegawa, M Ogura, H Kanema, N Noda, H Kawaharada, KJ Watanabe. Production of D-(3-hydroxyisobutyric acid from isobutyric acid by Candida rugosa and its mutant. J Fermen Technol 60 501-508, 1982. 

Polymerization of hexamethylcyclotrisiloxane with 3-butadienyllithium afforded butadienyl-ended polysiloxane macromonomer,20 [27], Polycondensation of a chiral methyl (3-hydroxyisobutyrate at a temperature higher than 150 °C with Ti(0-nBu)4 afforded directly a biodegradable polyester macromonomer, 21 [28]. 

C4H,jN02 13027-88-8) see Dimcthadionc D(-)-3-hydroxyisobutyric acid (C4Hb02 1910-47-0) see Captopril a-hydroxyisobutyric acid (C4H 04 594-61-6) see Diinethadione... 

For example, the method potentially opens an access to compounds with a doubly chiral isopropyl unit (Scheme 14). In the pro-5-selective enzymatic hydroxylation of isobutyric acid (88) to (S)-/3-hydroxyisobutyric acid (89) the stereochemistry of the hydroxylation at C-3 is not known. It could be studied by preparing 88 in a doubly chiral form via stereocontrolled ami-SN2 reaction of dimethyl cuprate with the tosy-late 90 to give 91 which is then degraded by Lemieux- and then Baeyer-Villiger oxidation to 88. 

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],...

Hydroxyisobutyric aciduria Methylmalonic acidemia Multiple carboxylase def. 

Hydroxyisobutyric aciduria 2-Ketoglutarate dehydrogenase complex def. Fumarase def. 

Methylmalonate semialdehyde dehydrogenase deficiency [8] has been described in a single patient. This patient, a boy, came to attention because of an elevated concentration of methionine on routine neonatal screening. The value exceeded 1000 imol/l. By 4 years of age he had developed normally. A valine load was followed by an increase in 3-hydroxyisobutyric acid excretion. Incubation of fibroblasts from the patient with 2-valine or p-[1- C]-alanine led to no production of C02 from valine and very little from )ff-alanine in contrast to control cells. 

Examination of plasma and urine revealed elevated quantities of jff-ala-nine, 3-hydroxypropionic acid, (R)- and (S)-3-aminoisobutyric acid, (R)-and (S)-3-hydroxyisobutyric acid and (S)-2-hydroxymethylbutyric acid. Direct enzymatic assay of methylmalonate semialdehyde dehydrogenase is unavailable revealed homozygosity for DNA analysis 1336 G>A transversion which substituted an arginine for a highly conserved glycine at amino acid residue 446. 

Hydroxyisobutyric aciduria and no defined defect in the methylmalo-nate semialdehyde dehydrogenase. 

Table 7.5. 3-Hydroxyisobutyric acidemia due to methylmalonate semialdehyde dehydrogenase deficiency...

Table 7.6. 3-Hydroxyisobutyric acidemia with normal methylmalonate semialdehyde dehydrogenase ...

Normal response no change in anything but valine concentration. Patient ketoacidosis HCO3, 10 mEq/1 3-hydroxybutyrate, 2-6 mmol/1. Modest decrease in glucose and increase in lactate in blood. Massive increase in 3-hydroxyisobutyrate in urine over 30% of administered valine recovered as 3-hydroxyisobutyrate. 

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