The relationship of the tricarboxylic acid cycle to the synthesis of δ-aminolaevulic acid in avian erythrocyte preparations

Abstract

A preparation of lysed normal chick erythrocytes has been described which actively synthesized [delta]-aminolevulic acid from glycine in the presence of various tricarboxylic acid cycle intermediates, but which does not produce porphobilinogen or porphyrins. The tricarboxylic acid cycle intermediates fall into the following decreasing order of effectiveness in [delta] -aminolevulic acid synthesis: isocitrate, citrate, [alpha]-oxoglutarate, succinate, oxaloacetate, malate and fumarate. Pyridoxal 5[image]-phosphate and coenzyme A stimulate the synthesis from all substrates examined. Adenosine triphosphate stimulates the production of [delta]-aminolevulic acid from succinate but slightly inhibits that from citrate, isocitrate and [alpha]-oxoglutarate. [alpha]-Lipoic acid enhances synthesis from citrate, isocitrate and [alpha]-oxoglutarate, but not from succinate. Use of the inhibitors fluorocitrate and parapyruvate shows that the interconversion of substrates before the formation of [delta]-aminolevulic acid is consistent with an active tricarboxylic acid cycle. Succinate inhibits the synthesis of [delta]-aminolevulic acid by suppressing the formation of succinyl-coenzyme A from citrate, isocitrate or [alpha]-oxoglutarate after itself being first converted into fumarate, malate or oxaloacetate. The inhibition is reversed by increasing concentrations of citrate or isocitrate, but is potentiated by [delta] -aminolevulic acid. 5,6-Dimethylbenzimidazole also inhibits the condensation of glycine and succinyl-coenzyme A. The inhibition here is partly relieved by increasing concentrations of glycine, but not by increasing concentrations of pyridoxal 5[image]-phosphate.