P-Hydroxyisovalerate

Urinary organic acid analysis is useful for differentiating isolated carboxylase deficiencies from the biotin-responsive multiple carboxylase deficiencies. P-Hydroxyisovalerate is the most common urinary metabolite observed in isolated P-methylcrotonyl-CoA carboxylase deficiency, biotinidase deficiency, biotin holo-carboxylase synthetase deficiency, and acquired biotin deficiency. In addition to P-hydroxy-isovalerate, elevated concentrations of urinary lactate, methylcitrate, and P-hydroxypropionate are indicative of multiple carboxylase deficiency. 

Hanson, R. L., Singh, I, Kissick, T. E, Patel, R. N., Szarka, L. I, and Mueller, R. H. 1990. Synthesis of L-P-hydroxyvaline from a-keto-P-hydroxyisovalerate using leucine dehydrogenase from Bacillus sp. Bioorg. Chem.,18,116-130. 

Figure 3-3 Structures of the K+ salts of (a) [p-hydroxyisovaleric acid-/V-methyl-L-valine]3 or enniatin B and (b) nonactin.

Sabourin PJ, Bieber LL. Formation of p-hydroxyisovalerate from a-ketoisocaproate by a soluble preparation from rat liver. Dev Biochem 1981 18 149-154. 

Sabourin PJ, Bieber LL. Subcellular distribution and partial characterization of an a-ketoisocaproate oxidase of rat liver formation of P-hydroxyisovaleric acid. Arch Biochem Biophys 1981 206 132-144. 

Sabourin PJ, Bieber LL. Formation of p-hydroxyisovalerate from a-ketoisocaproate by a soluble preparation from rat liver. In Metabolism and Clinical Implications of Branched Chain Amino and Ketoacids, Walser M, Williamson JR, Eds. Elsevier North Holland, New York, 1981, pp. 149-154. 

To date, over 80 naturally occurring trichothecenes have been identified and can be classified into three distinct structural groups Simple trichothecenes, macrocyclic trichothecenes and the recently discovered tri-choverroids. The simple trichothecenes, with 38 members, contain the basic mono- or polyhydroxylated sesquiterpene skeleton, with none, one, or more of the hydroxy groups esterified by acetic, crotonic, isovaleric, lactic or P-hydroxyisovaleric acid. This grouping can be further subdivided based on the oxidation level of C-8. Table I contains those simple sesquiterpenes in which C-8 is fully reduced. Table II is comprised of those members which possess an 8a-hydroxy group, while Table III lists all the compounds in... 

Figure 30 Enzymatic synthesis of chiral synthon for tigemonam Stereoselective reductive ami-nation of a-keto-P-hydroxyisovalerate 95.

A halo acid, p-(/S-bromoethyl)-benzoic acid (87%), a hydroxy acid, yS-hydroxyisovaleric acid (9%), and an acetylated amino acid, p-(/3-acetyl-aminoethyl)4>enzoic acid (78%), have been made by this method. Attempts to prepare 3-nitro- and 4-hydroxy-benzoic acids from the corresponding acetophenones have failed. Oxidation of the methylene group of 2-acetylfluorene occurs during the reaction to give fluorenone-2-car-boxylic acid (60%). ... 

A side product, 3-(2-hydroxy-3-methyl-butyrylamino)-propionic acid (HMBPA), can accumulate to high concentrations in the cultivation broth of (7 )-pantothenate-overproducing strains [177]. HMPBA formation is caused by premature a-KIV reduction to 2-hydroxyisovalerate (a-HIV) most probably by PanE before the molecule is hydroxymethylated (Figure 7.6). PanC-catalyzed condensation of a-HIV and P-alanine delivers HMBPA. 

A soln. of N-nitroso-N-methyl-L-isoleucyl-D-a-hydroxyisovaleric acid in abs. ether stirred 20 min. at 0° with PCI5, filtered, evaporated in vacuo at 30°, the residue dissolved in abs. ether, added dropwise with vigorous stirring at —10° during 15 min. to a soln. of p-nitrobenzyl N-methyl-L-isoleucyl-D-a-hydroxyiso-valerate and triethylamine in abs. ether, allowed to warm to room temp., and the product isolated after 2 hrs. p-nitrobenzyl N-nitroso-N-methyl-L-isoleucyl-D-a-hydroxyisovaleryl-N-methyl-L-isoleucyl-D- -hydroxyisovalerate. Y 93%. F. e. s. P. Quitt, P. O. Studer, and K. Vogler, Helv. 47, 166 (1964). 

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