Characterization and Measurement of Heme Synthetase in Normal Human Bone Marrow

Abstract

The heme synthetase step in human bone marrow has been characterized in a crude lysate as an enzymatic reaction in that it has a pH optimum of 7.4, is heat labile, and at optimum substrate concentrations is linear with time and enzyme concentration over the first 30 minutes. The Km of iron was found to be 1.7 x 10-5M and for protoporphyrin 1.8 x 10-6M. High iron concentrations do not affect the enzyme but ascorbic acid and glutathione were found to augment the activity of the enzyme. Pyridoxine and high protoporphyrin concentrations inhibit heme synthetase activity. A negative feedback control of heme synthetase by heme is present in human red cell precursors.

Ferrochelatase, glutathione peroxidase and transferrin receptor mRNA synthesis and levels in mouse erythroleukemia cells–mRNA synthesis and levels

“…Therefore, exogenous hemin could be a better iron donor for uninduced cells than for induced Friend cells, and this fact may partly clarify its effect. It is also known that hemin can inhibit ferrochelatase activity in human bone marrow cells [39] and in nonerythroid cells [40].…”

Intracellular Localization of 55Fe after Serum‐Mediated Uptake by Human Erythropoietic Cells

“…Most of the iron in these intracellular iron-transferrin complexes is known to be utilized for the synthesis of haem (Allen & Jandl 1960) but there is still uncertainty regarding some of the steps in the intracellular pathways followed by the iron before it finally becomes part of a functioning intracytoplasmic haemoglobin molecule. Two of the facts regarding this pathway which have been established are: (1) that the penultimate reaction in haem synthesis, namely the insertion of iron into the protoporphyrin IX ring, occurs within the mitochondria under the influence of the enzyme ferrochelatase (haem synthetase) which is tightly bound to the inner mitochondria1 membrane (Schwartz et a1 1959, Labbe & Hubbard 1960, Bottomley 1968, Jones & Jones 1969 and (2) that the transfer of the resulting haem from the mitochondria into the cytoplasm appears to require the participation of several poorly-characterised extramitochondrial proteins (Yoda & Israels 1972).…”

Erythropoietic protoporphyria.

“…Whether or not the anomaly is erythropoietic exclusively, or hepatic in part, could be decided by comparative studies of the enzymology of liver and bone-marrow biopsies. The former have been made by Bottomley (1968). Similar study of bone marrow is at present complicated by the difficulty of quantifying the amounts of erythroid tissue in the biopsy material.…”