Hydrazinopropionic acid: a new inhibitor of aminobutyrate transaminase and glutamate decarboxylase.
This paper deals with the synthesis of 3-pyrazolidone and the biochemical action of hydrazinopropionic acid. The latter compound is formed upon alkaline hydrolysis of 3-pyrazolidone. Hydrazinopropionic acid was found in vitro to be a very potent inhibitor of bacterial aminobutyrate transaminase as well as of aminobutyrate transaminase and glutamate decarboxylase from mouse brain. This inhibition was shown to occur despite the presence of high concentrations of pyridoxal phosphate in the incubation media. Injections of 20 mg hydrazinopropionic acid/kg into mice resulted in complete inhibition of aminobutyrate transaminase in brain and approximately 20 per cent inactivation of glutamate decarboxylase. This inhibition could not be prevented or antagonized by administration of pyridoxine to the animals. Addition of pyridoxal phosphate to homogenates of brain from animals treated with hydrazinopropionic acid also failed to reactivate the enzymes. The tentative conclusion reached from these results is that hydrazinopropionic acid has inhibitory action because of its close similarity to GABA with respect to molecular size, structural configuration and molecular charge distribution. This can be demonstrated by comparing a Dreiding model of hydrazinopropionic acid with that representing GABA.
van Gelder
N M
NM
Department of Pharmacology, Tufts University School of Medicine, Boston, Massachusetts, USA.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D051379:Mice; D011736:Pyridoxine / Q000494:pharmacology; D013997:Time Factors; D014803:Vitamin B Complex / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014803:Vitamin B Complex; C063864:hydrazinoacetic acid; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D011736:Pyridoxine; D005998:Glycine