Possible Occurrence of a Succinate-glycine Cycle in Rhodospirillum rubrum

Abstract

In Rhodospirillum rubrum it was shown that δ-aminolevulinate was actively metabolized through a new pathway in addition to the pathway for tetrapyrrole biosynthesis. The major metabolic products produced through the new pathway from [4-¹⁴C] δ-aminolevulinate were δ-amino-γ-hydroxyvalerate, α-hydroxyglutarate and glutamate. Based on the formation of α-hydroxyglutarate and glutamate, a cyclic pathway (a succinate-glycine cycle), which involves γ,δ-dioxovalerate and α-hydroxyglutarate as key intermediates, was proposed. Additional data in support of the proposed mechanism were as follows: (1) dioxovalerate was incorporated into glutamate in vivo as well in vitro; (2) [¹⁴C] glutamate formation from [4-¹⁴C] dioxovalerate in a cell-free system was strongly inhibited by D-α-hydroxyglutarate, indicating that the hydroxy acid is an intermediate; (3) [¹⁴C] glutamate derived from [4-¹⁴C] δ-aminolevulinate was preferentially labeled at its carbon-2. The existence of the succinate-glycine cycle was further substantiated by demonstration of two enzyme activities, a glyoxalase system [EC 4.4.1.5 and EC 3.1.2.6] and D-α-hydroxyglutarate dehydrogenase in cell-free extracts. Some properties of these enzymes were described. Of the reaction steps of the proposed pathway, only the enzymatic mechanism of dioxovalerate formation from δ-aminolevulinate remains to be elucidated. The possible significance of the succinate-glycine cycle in regulating tetrapyrrole biosynthesis was discussed.