The regulatory effect of heme on erythroid aminolevulinate synthase in natural erythroid cells

A major enzymatic pathway in erythroid cells is the eight-step formation of heme, starting with the erythroid isoform of aminolevulinate synthase (eALAS). We studied the regulation of eALAS synthesis by heme in natural erythroid cells. Erythroid cells from mouse blood or bone marrow were incubated with different concentrations of heme and labelled with [ 35S]methionine. This was followed by immunoprecipitation of eALAS proteins. Northern blot analysis was done on mRNA isolated from bone marrow. Incubation with heme (5–100 μM) was shown to clearly inhibit eALAS synthesis in erythroid cells of bone marrow. This inhibitory effect of heme could also be observed in peripheral blood cells at higher concentrations while the preform of eALAS was rather increased. However, at lower concentrations of heme (1–10 μM), eALAS synthesis increased. Northern blot studies argued the inhibitory effect was at the posttranscriptional level. Our results suggest that the net effect of murine eALAS regulation by heme varies with the degree of erythroid differentiation. Heme formation seems to be more tightly controlled in the bone marrow (nucleated) cells in order to prevent oxidative cell damage, compared to more differentiated erythroid cells.