Heme Synthase (Ferrochelatase) Catalyzes the Removal of Iron from Heme and Demetalation of Metalloporphyrins

Abstract

The red pigments in meat products, including cooked cured ham, arise from the reaction of myoglobin with nitric oxide generated from exogenous nitrite. Since carcinogenic nitrosoamines may be generated by the treatment of meats with nitrite, the production of nitrite-free meat products is an attractive alternative. Raw dry-cured (Parma) hams are produced by the treatment of meats with salts other than nitrite. Analysis of pigments in raw dry-cured hams reveals that the main pigment is zinc protoporphyrin, suggesting that the conversion of heme to zinc protoporphyrin occurs via an iron-removal reaction from myoglobin heme during the processing of raw hams. Purification of the iron-removal enzyme showed that it was identical to ferrochelatase. Recombinant ferrochelatase in combination with NADH-cytochrome b5 reductase catalyzed NADH-dependent iron-removal reaction from hemin and hemoproteins. Metal ions such as zinc and cobalt were also removed from the corresponding metalloporphyrins. The addition of zinc ions led to the formation of zinc protoporphyrin. In cultured cells, the conversion of zinc mesoporphyrin to mesoheme was observed to be dependent on ferrochelatase and could be markedly induced during erythroid differentiation. This is the first demonstration of a new enzyme reaction, the reverse reaction of ferrochelatase, which may contribute to a new route of the recycling of protoporphyrin and heme in cells.

Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact

“…In 2 cases, ferrochelatases from meat (21) and from Haemophilus influenzae (22) have been shown to catalyze the reverse reaction in vitro in the presence of reductants. However, YfeX and EfeB do not have significant sequence similarities to any known ferrochelatase and thus most likely have evolved separately to achieve the reaction by a mechanism distinct from ferrochelatases.…”

Porcine Ferrochelatase: The Relationship between Iron-Removal Reaction and the Conversion of Heme to Zn-Protoporphyrin

“…Hemin-imidazole was prepared as previously described. 10) Pig kidney LLC-PK1 cells were obtained from the Japan Cell Bank (Saitama, Japan). Porcine livers and muscles were generously donated by Itoh Ham Inc. (Moriya, Japan).…”

“…8,9) Therefore, reutilization of iron, including degradation of the heme, catalyzed by heme oxygenase, is essential for the homeostasis of iron in cells. Recently, we reported that the removal of ferrous ions from heme occurred in vivo, and that FECH removed iron from heme in vitro, 10) but the role of the reaction in removing iron in vivo is not clear.…”

“…Drycured ham (Parma ham), which is nitrite-free, is made from porcine muscle with only sea salt at a suitable temperature for long periods. 13) The main component of the red pigment of the ham has been found to be Zn-protoporphyrin, 10,14) a pigment stable under air exposure and heating. 15) Although the mechanism involved in the formation of Zn-protoporphyrin during the production of dry ham is unclear, formation in the muscle may be related to mitochondria and enzyme catalysis.…”

“…15) Although the mechanism involved in the formation of Zn-protoporphyrin during the production of dry ham is unclear, formation in the muscle may be related to mitochondria and enzyme catalysis. 16) Very recently, we found that FECH is involved mainly in the formation of Zn-protoporphyrin via iron-removal reverse reaction, 10) but little attention has been paid to the characteristics and kinetic properties of the reverse reaction of FECH.…”