Cellular Zinc Deficiency Impairs Heme Biosynthesis in Developing Erythroid Progenitors

Juyoung Kim, Jaekwon Lee, Moon Suhn Ryu

Research output: Contribution to journalArticlepeer-review


Anemia is the most prevalent nutrition-related disorder worldwide. Zinc is an essential trace element for various biological processes in the body, and zinc deficiency has been associated with anemia in humans. However, the molecular mechanisms by which zinc availability alters red blood cell development remain uncertain. The present study identifies the essentiality of zinc during erythroid development, particularly for normal heme biosynthesis. G1E-ER4 mouse cells were used as an in vitro model of terminal erythroid differentiation, which featured elevated cellular zinc content by development. Restriction of zinc import compromised the rate of heme and α-globin production and, thus, the hemoglobinization of the erythroid progenitors. Heme is synthesized by the incorporation of iron into protoporphyrin. The lower heme production under zinc restriction was not due to changes in iron but was attributable to less porphyrin synthesis. The requirement of adequate zinc for erythroid heme metabolism was confirmed in another erythropoietic cell model, MEL-DS19. Additionally, we found that a conventional marker of iron deficiency anemia, the ZnPP-to-heme ratio, responded to zinc restriction differently from iron deficiency. Collectively, our findings define zinc as an essential nutrient integral to erythroid heme biosynthesis and, thus, a potential therapeutic target for treating anemia and other erythrocyte-related disorders.

Original languageEnglish
Article number281
Issue number2
Publication statusPublished - 2023 Jan

Bibliographical note

Funding Information:
This study was supported by the Allen Foundation Grant and the Yonsei University Research Fund of 2021-22-0341 to M.-S.R., and by the National Institutes of Health grant DK079209 to J.L.

Publisher Copyright:
© 2023 by the authors.

All Science Journal Classification (ASJC) codes

  • Food Science
  • Nutrition and Dietetics


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