Characterization and measurement of heme synthetase in normal human bone marrow.

T HE INSERTION OF IRON into protoporphyrin is the final step of a series of reactions in the biosynthesis of heme.’ Several previous investigations have demonstrated that this step is enzyme-dependent and the enzyme has been named Theme synthetase” or “iron chelatase.” The enzyme has been extensively characterized in rat liver mitochondria,2 and Porra and Jones suggested that two enzymes may be involved in the reaction.3 The enzymic biosynthesis of heme from iron and protoporphyrin in erythroid tissue has mainly been described in avian erythrocyte lysates.46 Langelaan, Losowsky and Toothill7 have recently demonstrated heme synthetase activity and some properties of the enzyme in normal human peripheral blood. Decreased heme synthetase activity in peripheral blood has been reported in one patient with pyridoxine-responsive anemia8 and also in several types of hematological disorders.9 Lochhead and Goldberg’#{176} measured heme synthetase in water lysates of human bone marrow and 5teiner’ ‘ has described low heme synthetase activity in water lysates of bone marrow from patients with thalassemia. In the present studies, a method for assay of heme synthetase in human bone marrow was developed. Employing this procedure, the enzyme was characterized. Values for activity of the enzyme in normal marrow were established and, in part, confirm the work of Steiner.” In addition, some factors affecting the activity of the enzyme are described. A preliminary report of these findings has been made.’2