Effect of phosphonic analogues of glutamic acid on glutamate decarboxylase

Abstract

Among the phosphonic analogues of glutamic acid, only 4-amino-4-phosphono butyric acid, the compound which shows the highest affinity for pyridoxal phosphate, inhibits competitively both Escherichia coli and rat brain glutamate decarboxylases. Phosphinothricin, 2-amino-4-(methylphosphino)butyric acid, is a strong inhibitor of the mammalian enzyme.

A Case of Transient Diabetes Insipidus Associated with Poisoning by a Herbicide Containing Glufosinate

“…Also, glufosinate inhibits glutamate decarboxylase, an enzyme that catalyzes the formation of γ-aminobutyric acid (GABA) from glutamate in vitro. 10 Our patient ingested an extremely large volume (500 mL) of undiluted BASTA herbicide and despite the unquantified loss from repeated vomiting, the serum level of glufosinate was extremely high compared with those reported in previous cases. 1 At these high levels, glufosinate might possibly have had severe effects on brain tissues.…”

Phosphonic analogues of tyrosine and 3,4-dihydroxyphenylalanine (dopa) influence mushroom tyrosinase activity

“…The inhibition frequently observed indicates that there is a structural antagonism between amino acids and their phosphonic counterparts and that numerous enzymes do recognize amino phosphonates as being more or less similar to the respective amino carboxylates. The most conspicuous examples are provided by the strong inhibition of glutamate-ammonia ligase (glutamine synthetase) (Meek & Villafranca, 1980;Lejczak et al, 1981;Leason et al, 1982), dipeptidyl carboxypeptidase I (Petrillo & Spitzmiller, 1979), adenylosuccinate lyase (Brand & Lowenstein, 1978) and alanine racemase (Adams et al, 1974;Lacoste et al, 1985) by compounds that differ from the respective substrates only by having a phosphonic or phosphinic acid function in place of a carboxylic group. Apparently these enzymes bind amino phosphonates preferentially over their amino carboxylate substrates.…”

“…Several examples indicate that many enzymes do not differentiate between CO2H and PO3H2 functions as concerns the binding to active sites (Anderson & Fowden, 1970;Lacoste et al, 1972;Biryukov et al, 1978;Brand & Lowenstein, 1978;Iron et al, 1981; Lejczak et al, 1985; Lacoste et al, 1985).…”

The Metabolites of the Herbicide L-Phosphinothricin (Glufosinate) (Identification, Stability, and Mobility in Transgenic, Herbicide-Resistant, and Untransformed Plants)

“…The toxicology of t-Pt has been intensively analyzed (Lejczak et al, 1981;Lacoste et al, 1985;Dom et al, 1986;Logusch et al, 1989) and was summarized by Ebert et al (1990). It is safe under the conditions of recommended use, but, according to European Economic Community directive 83/467/EEC, it has to be classified as harmful on the basis of testing for acute oral toxicity (Ebert et al, 1990).…”