Heme as key regulator of major mammalian cellular functions: Molecular, cellular, and pharmacological aspects
Abstract
Heme (iron protoporphyrin IX) exists as prosthetic group in several hemoproteins, which include respiration cytochromes, gas sensors, P450 enzymes (CYPs), catalases, peroxidases, nitric oxide synthases (NOS), guanyl cyclases, and even transcriptional factors. Hemin (the oxidized form of iron protoporphyrin IX) on the other hand is an essential regulator of gene expression and growth promoter of hematopoietic progenitor cells. This review is focused on the major developments occurred in this field of heme biosynthesis and catabolism and their implications in our understanding the pathogenesis of heme-related disorders like anemias, acute porphyrias, hematological malignancies (leukemias), and other disorders. Heme is transported into hematopoietic cells and enters the nucleus where it activates gene expression by removing transcriptional potential repressors, like Bach1, from enhancer DNA sequences. Evidence also exists to indicate that heme acts like a signaling ligand in cell respiration and metabolism, stress response adaptive processes, and even transcription of several genes. Impaired heme biosynthesis or heme deficiency lead to hematological disorders, tissue degeneration, and aging, while heme prevents cell damage via activation of heme oxygenase-1 (HO-1) gene. Therefore, heme, besides being a key regulator of mammalian functions, can be also a useful therapeutic agent alone or in combination with other drugs in several heme-related disorders.
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In mammals, most iron is present as heme, a hydrophobic iron-containing tetrapyrrole that binds iron through nitrogen atoms.
“In mammals, the large majority of Fe exists in the form of heme, a hydrophobic Fe-based compound in which four methane-bridged pyrroles form a tetrapyrrole ring that binds Fe through nitrogen atoms (7, 8).”
From Innate Nutritional Immunity (2018) · cites this paper as [7]
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- Authors
- Tsiftsoglou, A. S., Tsamadou, A. I., & Papadopoulou, L. C.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- Corresponding author
- Tsiftsoglou, Asterios S.
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 111
- Issue
- 2
- Pages
- 327-345
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W2035707213
- Cited by
- 281
- References
- 186
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 19 · 2023: 9 · 2022: 15 · 2021: 11 · 2020: 14 · 2019: 12 · 2018: 13 · 2017: 16 · 2016: 12 · 2015: 19 · 2014: 20 · 2013: 14 · 2012: 15
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Secretaría de Ciencia y Técnica, Universidad de Buenos Aires
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- heme, heme biosynthesis, heme degradation, heme oxygenase-1, anemia, acute porphyria, hematologic malignancies, heme proteins, cytochromes, cytochrome P450, nitric oxide synthase, guanylate cyclase, transcriptional regulation, BACH1, stress response, aging, therapeutic agents
- MeSH terms
- Animals, Cell Differentiation, Heme, Hemeproteins, Hemin, Humans, Signal Transduction, Cell Proliferation
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