Aminomalonate as an enzyme inhibitor

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Abstract
Aminomalonate combines with acetyl-acetone, but not with ethyl acetoacetate, to form an Ehrlich-positive compound, which is probably 2-carboxy-3,5-dimethylpyrrole. Monomethyl and monoethyl aminomalonate have been synthesized, and aminomalonic acid monoamide has been prepared by a new route. The non-enzymic condensation of aldehydes with aminomalonate and related compounds under the catalytic influence of pyridoxal has been studied. The aldol condensation occurs under milk conditions and leads ultimately to [alpha]-amino-[beta]-hydroxy acids. In acid solution the principal reaction catalysed by pyridoxal is decarboxylation. Aminomalonate was a powerful competitive inhibitor of aminolaevulate synthetase from Rhodopseu-domonas spheroides and avian erythrocyte particles. The mono- and di-esters of aminomalonate were moderate inhibitors and aminomalonic acid monoamide was a weak inhibitor of the enzyme. Inhibition by aminomalonate was somewhat dependent on the concentration of pyridoxal phosphate. Serine hydroxymethyltransferase was fairly strongly inhibited by aminomalonate. Glycine acyltransferase and phosphoribosylglycina-znlde synthetase were slightly inhibited by amino-malonate, but tyrosine decarboxylase and aspartate aminotransferase were not inhibited by this compound. The mechanism of inhibition of aminolaevulate synthetase by aminomalonate and other compounds is discussed.