Phosphinothricin

Uses

Glufosinate, a phosphinic acid analogue of glutamic acid, is a herbicide which is converted by plant cells into PT (L-phosphinothricin). Glufosinate exerts neurotoxic activity[1][2].

Definition

ChEBI: 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid is a non-proteinogenic alpha-amino acid that is 2-aminobutanoic acid which is substituted at position 4 by a hydroxy(methyl)phosphoryl group. It is a member of phosphinic acids and a non-proteinogenic alpha-amino acid.

in vivo

Enzyme inhibitor

This dephospho transition-state analogue (FW = 177.10 g/mol; CAS 51276- 47-2) is naturally occurring glutamate analogue, first isolated from Streptomyces viridochromogenes. Phosphonothricin is a slow, tight-binding inhibitor of glutamine synthetase that binds at the glutamate binding site and stabilizes the flap of a glutamyl residue in a position blocking glutamate entry into the active site, thereby trapping the inhibitor on the enzyme. Phosphinothricin undergoes an ATP-dependent phosphorylation. Note: Phosphinothricin is a component of the antibiotics bialaphos and phosalacine. The monoammonium salt of the racemic compound, also called glufosinate-ammonium, is a post-emergent herbicide.

Metabolic pathway

When 14C-phosphinothricin [homoalanin-4-yl- (methyl)phosphinic acid] is incubated in the cell suspension cultures of soybean, wheat, and maize, in maize cells which take up to 50% of the applied radioactivity, four different metabolites are detected which are identified as 4-methylphosphinico-2-oxo- butyric acid, 4-methylphosphinico-2-hydroxybutyric acid, 4-methylphosphinicobutyric acid, and 3- methylphosphinicopropionic acid. In soybean and wheat cultures, 10 and 6% of the applied radioactivity is taken up, respectively. In soybean, only one metabolite, 3-methylphosphinicopropionic acid, is detected, whereas in wheat, 4-methyl- phosphinicobutyric acid is additionally present.

References

[1] áy Z, et al. The effect of high concentrations of glufosinate ammonium on the yield components of transgenic spring wheat (Triticum aestivum L.) constitutively expressing the bar gene. ScientificWorldJournal. 2012;2012:657945. DOI:10.1100/2012/657945
[2] Feat-Vetel J, et al. Multiple effects of the herbicide glufosinate-ammonium and its main metabolite on neural stem cells from the subventricular zone of newborn mice. Neurotoxicology. 2018 Dec;69:152-163. DOI:10.1016/j.neuro.2018.10.001
[3] Ebert E, et al. Summary of safety evaluation toxicity studies of glufosinate ammonium. Food Chem Toxicol. 1990 May;28(5):339-49. DOI:10.1016/0278-6915(90)90108-y