Hydroxybutyric acid, conversion

One of the classic examples of a reversible reaction that is first-order in both directions is the conversion of y-hydroxybutyric acid into its lactone in aqueous solution. 

Gold, B.I. Roth, R.H. (1977) Kinetics of in vivo conversion of ganuna-l HJaminobutyric acid to gamma-[3H]hydroxybutyric acid by rat brain. J. Neurochem., 28, 1069-1073... 

Roth, R.H. Giarman, N.J. (1969) Conversion in vivo of gamma-aminobutyric to gamma-hydroxybutyric acid in the rat. Biochem. Pharmacol., 18,247-250... 

One of the classical examples of a reversible reaction is the conversion of y-hydroxybutyric acid into its lactone in an aqueous solution. In aqueous solution, the water concentration may be considered constant, so the reverse reaction follows pseudo-first-order kinetics. The following data were obtained. Determine the values of both first-order rate constants (forward and reverse). The initial acid concentration is 182.3 mol/L. 

An enzymatic process has been developed for the preparation of 4-halo-3-hydroxybutyric acid derivatives by ketoreductase-catalyzed conversion of 4-... 

Example 5.1. Reversible formation of a lactone. Results obtained for the conversion of 7-hydroxybutyric acid into its lactone... 

Figure 5.4. Conversion of y-hydroxybutyric acid into its lactone, plotted as reversible first order-first order reaction (left) and as irreversible reaction of order 1.5 (right).

In known metabolic states and disorders, the nature of metabolites excreted at abnormal levels has been identified by GC-MS. Examples of this are adipic and suberic acids found in urine from ketotic patients [347], 2-hydroxybutyric acid from patients with lactic acidosis [348], and methylcitric acid (2-hydroxybutan-l,2,3-tricarboxylic acid) [349] in a case of propionic acidemia [350,351]. In the latter instance, the methylcitric acid is thought to be due to the condensation of accumulated propionyl CoA with oxaloacetate [349]. Increased amounts of odd-numbered fatty acids present in the tissues of these patients due to the involvement of the propionyl CoA in fatty acid synthesis, have also been characterised [278]. A deficiency in a-methylacetoacetyl CoA thiolase enzyme in the isoleucine pathway prevents the conversion of a-methylacetoacetyl CoA to propionyl CoA and acetyl CoA [352,353]. The resultant urinary excretion of large amounts of 2-hydroxy-3-methylbutanoic acid (a-methyl-/3-hydroxybutyric acid) and an excess of a-methylacetoacetate and often tiglyl glycine are readily detected and identified by GC-MS. 

Similarly, the conversion of a homologous substrate has been demonstrated by using lactate oxidase. 2-Hydroxybutyric acid was measured with a lactate oxidase electrode with a sensitivity comparable with that for the normal substrate, lactate. 

The amide group of 16 can be converted to a nitrile with acetic anhydride in pyridine at room temperature to give the relatively unstable acid 18. Immediate hydrogenation of the nitrile with platinum oxide furnishes ( S)-4-amino-2-hydroxybutyric acid (19) in 30% overall yield (Scheme 1). Conversion of 18 to the stable benzhydryl ester 20 is accomplished by treatment with diazodiphenylmethane (84% yield) [26]. 

Consider the conversion of y-hydroxybutyric acid (A) into its lactone (L) in aqueous solution ... 

The metabolic pathways involved in the synthesis of P(3HB-co-4HB) from 4-hydroxybutyric acid are shown in Fig. 2.4. Transferase or thiokinase catalyzes the conversion of 4-hydroxybutyric acid into 4HB-CoA, which is then used as the substrate by the PHA synthase in the polymerization reaction. The catabolism of 4-hydroxybutyric acid also leads to the formation of intermediates such as 3-hydroxybutyryl-CoA, resulting in the accumulation of P(3HB-co-4HB) copolymer. The main catabolic pathway for 4HB is probably via succinic acid semialdehyde and succinic acid pathways, which are catalyzed by 4HB dehydrogenase and succinic acid semialdehyde dehydrogenase (Valentin et al. 1995 Lutke-Eversloh and Steinbiichel 1999). All precursor substrates for the generation of 4HB monomers are first converted into 4HB-CoA, which is the immediate substrate for PHA synthase. 

In trying to form a polyester from gamma-hydroxybutyric acid, what percent conversion is required to obtain a molecular weight of 25000. 

The conversion of acetoacetic acid to hydroxybutyric acid restitutes the 4-carbon compounds to the general metabolism because the liver contains enzymes that will activate jS-hydroxybutyric acid to yield j8-hydroxybutyric CoA, whereas acetoacetic acid cannot be acylated by the liver. 

Sajewicz, M., Kronenbach, D., Gontarska, M., and Kowalska, T. 2010. TLC and polari-metric investigation of the oscillatory in vitro chiral conversion of r-P-hydroxybutyric acid, J. Liq. Chromatogr. Relat. Technol., 33 1047-1057. 

Five-membered, unsubstituted, lactone y -butyrolactone (y-BL) was polymerised by PPL or PCL [74, 81] into small oligomers with a DP of 8-11. More recently, y-BL have yielded homopolymers of up to 50,000 [82]. Poly(y-butyrolactone) is a very useful biomaterial, since its degradation gives y-hydroxybutyric acid, a metabolite naturally occurring in the body. In the PSL-catalysed polymerisation of y-valerolactone (y-VL) and y-caprolactone (y-CL), less than 10% conversion was observed at 60 °C for 480 h [76]. 

Upon incubating rat liver extracts with DL-homoserine-2-C Matsuo et al. (74) demonstrated that the immediate reaction product was butyric acid. This compound was in part transaminated to a-aminobutyric acid and in part reduced to a-hydroxybutyric acid. Further d radation was accomplished by its decarboxylation to propionic acid. The complete oxidation then proceeds through conversion to succinic acid and the operation of the TCA cycle. 

Microbial or enzymatic conversion of renewable resources Lactic acid Succinic acid 1.3- Propanediol Itaconic acid 2.3- Butanediol 3-Amino-4-hydroxy- benzoic acid Amino acids Glucose Trehalose Glucaric acid Erythritol P-Hydroxybutyric acid P-Hydroxypropionic acid Itaconic acid Isoprene ... 

Figure 3 also shows the pathway of 4-hydroxybutyrate synthesis from 4-hydroxybutyric acid (Pathway V) [81, 143]. 4-Hydroxybutyryl-CoA is first formed, and part of it is polymerized by PHA synthase. A portion of the hydroxyacyl-CoA is however dehydrated to the corresponding enoyl-CoA, which enters the pathway of 3HB synthesis via R-3-hydroxybutyryl-CoA. According to Valentin et al. [136] it is more likely that formation of 3-hydroxybutyryl-CoA occurs via succinate semialdehyde, succinate, pyruvate, and acetyl-CoA from 4-hydroxybutyrate. A copolymer of 3HB and 4HB is thus usually produced from 4HB acid. Presence of butyric acid in the medium somewhat inhibits the conversion of 4-hydroxybutyryl-CoA into R-3-hydroxybutyryl-CoA. The apparently complete inhibition of 3HB synthesis from 4HB acid by citrate and ammonium sulfate observed by Nakamura et al. [92] has to date not been explained. Substrates which can be converted to 4-hydroxybutyric acid, such as y-butyrolactone, 1, 4-butanediol, 1, 6-hexanediol, and 4-chlorobutyric acid, also lead to the formation of 4HB monomers [143]. 

---