The regulation of heme biosynthesis.

Changes in the levels of the heme biosynthetic enzymes were studied in cells and protoplasts of Saccharomyces cerevisiae during glucose derepression and respiratory adaptation. On aerobic or anaerobic glucose derepression or in the presence of 3', 5' cyclic AMP the levels of beta-aminolevulinic acid dehydratase, protoporphyrinogen oxidase and ferrochelatase increased whereas the levels of the enzymes catalysing the reactions from porphobilinogen to protoporphyrinogen IX remained constant. In contrast, the level of beta-aminolevulinic acid synthetase decreased during aerobic glucose derepression and in the presence of 3', 5' cyclic AMP, but it remained unchanged during anaerobic derepression. The heme content of the cells increased during aerobic glucose derepression but no increase was observed during anaerobic derepression of the cells. It is concluded that, in yeast, the inhibitory effect of anaerobiosis on heme synthesis is due, at least in part, to the requirement for oxygen in the oxidation of protoporphyrinogen IX, and that the effect of glucose on heme biosynthesis is mediated via glucose repression of protoporphyrinogen oxidase and possibly ferrochelatase.