A study was made of the control of the enzyme 5-aminolaevulinate synthetase in the photosynthetic micro-organism R. spheroides.

The spontaneous activation of the enzyme in cell-free extracts and the suppression of this activation by culture oxygenation have been investigated. It was found that oxygenation is associated with a major disturbance of the sulphur metabolism of the organisms;​ the major intracellular amino sulphur compound, glutathione, is degraded and the cysteine released is metabolized to homolanthionine;​ there is a release of inorganic sulphate from the cells into the medium and a 60-70% fall in the total intracellular "free -SH". Suspension of cells in sulphate-deficient media produced a similar disturbance of sulphur metabolism and also suppressed the activation of ALA synthetase.

It was then shown that a number of culture treatments which prevented the effect of culture oxygenation on ALA synthetase, also prevented its effect on the sulphur metabolism of the organisms. Moreover, it was found that the total glutathione and "cysteine plus cystine" content of extracts was always directly correlated with the degree of spontaneous activation of ALA synthetase which would occur in the extract.

The "low" activity enzyme in glutathione depleted extracts was found to be activated by added glutathione, cysteine or cystine;​ the "high" activity enzyme was, however, unaffected by these sulphur compounds. Purification of the "low" activity enzyme indicated that added sulphur compounds were not interacting directly with the enzyme.

A low molecular weight activator of "low" activity ALA synthetase has been purified from R. spheroides. The compound was not positively identified but all of its properties are consistent with it being a pteridine. Evidence was obtained that the activator produces its effect by direct interaction with the enzyme. An inhibitor of "high" activity ALA synthetase has also been purified from R. spheroides.

Hypotheses have been presented for the pathway of sulphur metabolism in R. spheroides and the mechanism of the spontaneous activation of ALA synthetase. On this basis the control of ALA synthetase activity and tetrapyrrole biosynthesis in R. spheroides has been discussed.