Sodium phenylpyruvate

Biological Activity

Sodium phenylpyruvate (Phenylpyruvic acid sodium salt) inhibits amino acid formation and depresses oxygen consumption.

Enzyme inhibitor

This aromatic a-keto acid and PKU biomarker (FWfree-acid = 164.16 g/mol; CAS 156-06-9 for acid; CAS 114-76-1 for sodium salt; CAS 51828-93-4 for calcium salt); lmax = 320 nm, e = 17500 M–1 cm–1 in 0.7 M NaOH), also known as 2-oxo-3-phenylpropanoic acid and a-oxohydrocinnamic acid, is readily formed by the action of a number of aminotransferases on phenylalanine. Phenylpyruvate is only slightly soluble in boiling water but is soluble in ethanol and diethyl ether. The solid oxidizes in air and decomposes on storage, if not dry. Sodium phenylpyruvate is a watersoluble monohydrate salt. Phenylketonuria: Phenylpyruvate is present at high urinary concentrations in phenylalanine monooxygenase deficiency, better known as Phenylketonuria. Indeed, individuals suffering PKU tend to excrete urine containing large quantities of phenyl-pyruvate, phenyl-acetate and phenyl-lactate, along with phenylalanine. If untreated, mental retardation and microcephaly are evident by the first year, along with irritability, epileptic seizures, and skin lesions. Target(s): acetolactate synthase; aldehyde reductase; apyrase; branched-chain a-keto acid dehydrogenase; [branched-chain a-keto-acid dehydrogenase] kinase, or [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase; carnitine-acylcarnitine translocase; cathepsin D; choline acetyltransferase; 3-deoxy-7-phosphoheptulonate synthase, or 3-deoxy-D-arabino-heptulosonate 7-phosphate synthetase; dihydropteridine reductase; diphosphomevalonate decarboxylase; glutamate decarboxylase; glutamine:pyruvate aminotransferase; glycerate dehydrogenase, weakly inhibited; hexokinase (human brain), Ki = 2 mM; histidine decarboxylase; 4- hydroxyphenylpyruvate dioxygenase; 3a-hydroxysteroid dihydrogenase; 3b-hydroxysteroid dehydrogenase; hypothalamus acid proteinase; indolepyruvate decarboxylase, Ki = 50 μM; kynureninase; L-lactate dehydrogenase; L-lactate dehydrogenase (cytochrome); mercaptopyruvate sulfurtransferase; mevalonate-5-pyrophosphate decarboxylase; oxaloacetate tautomerase; phenylalanine ammonia-lyase; phenylalanyltRNA synthetase, weakly inhibited, Ki = 7.6 mM; pyruvate carboxylase; pyruvate decarboxylase; pyruvate dehydrogenase; pyruvate kinase (human), Ki = 8.5 mM; pyruvate oxidase; pyruvate transport; stearoyl-CoA 9-desaturase; tryptophan 2- monooxygenase; tryptophan 5-monooxygenase; tyrosinase; and tyrosine 2,3-aminomutase.

Purification Methods

The salt should have no OH broad bands in the IR at ~3000cm-1. If these are present, then they are due either to water contamination or to the presence of free acid. For the first case dry the solid thoroughly in a vacuum over P2O5, and in the latter case wash the salt well with Et2O in vacuo till free of acid. Alternatively add a slight excess of the free acid (cf p 332) in EtOH to ethanolic NaOH, evaporate to dryness and extract excess acid from the salt with dry Et2O. [Beilstein 10 I 325.]