Ferric pyridoxal isonicotinol hydrazone can provide iron for heme synthesis in reticulocytes |
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Authors: | Premysl Ponka Herbert M Schulman Ania Wilczynska |
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Institution: | 1. Department of Physiology and Division of Hematology, McGill University, Canada;2. Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Saint Catherine Road, Montreal, Quebec H3T 1E2, Canada |
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Abstract: | We have examined whether reticulocytes depleted of transferrin might incorporate 59Fe from 59Fe-labelled pyridoxan isonicotinoyl hydrazone (PIH). Transferrin-depleted reticulocytes showed a time-, temperature- and concentration-dependent incorporation of 59Fe when incubated with 20–200 μM 59Fe-PIH. The amount of 59Fe incorporated with 200 μM 59Fe-PIH is equal to or higher than that taken up from transferrin at 20 μM 59Fe concentration. After 60 min about 60% of the 59Fe taken up by the cells is recovered in heme while the remainder is probably still bound to PIH. 1 mM succinyl acetone (a specific inhibitor of heme synthesis) inhibits PIH-mediated incorporation of 59Fe into heme by about 79% indicating that 59Fe from 59Fe-PIH is incorporated into de novo synthesized protoporphyrin. As is the case with transferrin, erythrocytes do not incorporate 59Fe from 59Fe-PIH. Pretreatment of reticulocytes with pronase does not inhibit their ability to incorporate 59Fe from 59Fe-PIH, suggesting that, unlike the uptake of Fe from transferrin, membrane receptors are not involved in the uptake of Fe-PIH by the cells. |
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Keywords: | Hydrazone derivative Iron source Heme synthesis (Reticulocyte) |
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