Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (690 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Ferroprotoporphyrin; Heme b; Protoheme; Protoheme IX; Haem.
Where it fits in the MeSH classification
- Broader topics
- Metalloporphyrins
- Narrower topics
- Hemin
Research landscape
PubMed indexes 23,927 records tagged with the MeSH heading “Heme” (counts retrieved 2026-10-31). 3,119 of them (13.0%) were published from 2020 onward, and the busiest period so far is through 1999 with 10,411 records.
Reviews account for 2,104 records (8.8%) and meta-analyses for 17. Randomized controlled trials number 72 (0.3%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 10,411 |
| 2000-2009 | 5,238 |
| 2010-2019 | 5,159 |
| 2020 onward | 3,119 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,104 | 8.8% |
| Meta-analyses | 17 | 0.1% |
| Randomized controlled trials | 72 | 0.3% |
Method: PubMed query "Heme"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Design of Heme Enzymes with a Tunable Substrate Binding Pocket Adjacent to an Open Metal Coordination Site | 2023 | Research article Design not recorded in structured metadata | 70 | cc by PMID 37341421 · DOI · PMC10326885 |
| Highly stable and tunable peptoid/hemin enzymatic mimetics with natural peroxidase-like activities | 2022 | Research article Design not recorded in structured metadata | 56 | cc by PMID 35641490 · DOI · PMC9156750 |
| Mitoferrin, Cellular and Mitochondrial Iron Homeostasis | 2022 | Review article Design not recorded in structured metadata | 52 | cc by PMID 36359860 · DOI · PMC9658796 |
| Proteasome-guided haem signalling axis contributes to T cell exhaustion | 2026 | Research article Design not recorded in structured metadata | 5 | cc by PMID 41851457 · DOI · PMC13658038 |
Design of Heme Enzymes with a Tunable Substrate Binding Pocket Adjacent to an Open Metal Coordination Site [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The catalytic versatility of pentacoordinated iron is highlighted by the broad range of natural and engineered activities of heme enzymes such as cytochrome P450s, which position a porphyrin cofactor coordinating a central iron atom below an open substrate binding pocket.
- Closing excerpt
- Our approach now enables the custom design of enzymes containing cofactors adjacent to binding pockets with an almost unlimited variety of shapes and functionalities.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (227 words)
The catalytic versatility of pentacoordinated iron is highlighted by the broad range of natural and engineered activities of heme enzymes such as cytochrome P450s, which position a porphyrin cofactor coordinating a central iron atom below an open substrate binding pocket. This catalytic prowess has inspired efforts to design de novo helical bundle scaffolds that bind porphyrin cofactors. However, such designs lack the large open substrate binding pocket of P450s, and hence, the range of chemical transformations accessible is limited. Here, with the goal of combining the advantages of the P450 catalytic site geometry with the almost unlimited customizability of de novo protein design, we design a high-affinity heme-binding protein, dnHEM1, with an axial histidine ligand, a vacant coordination site for generating reactive intermediates, and a tunable distal pocket for substrate binding. A 1.6 Å X-ray crystal structure of dnHEM1 reveals excellent agreement to the design model with key features programmed as intended. The incorporation of distal pocket substitutions converted dnHEM1 into a proficient peroxidase with a stable neutral ferryl intermediate. In parallel, dnHEM1 was redesigned to generate enantiocomplementary carbene transferases for styrene cyclopropanation (up to 93% isolated yield, 5000 turnovers, 97:3 e.r.) by reconfiguring the distal pocket to accommodate calculated transition state models. Our approach now enables the custom design of enzymes containing cofactors adjacent to binding pockets with an almost unlimited variety of shapes and functionalities.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37341421 · DOI · PMC10326885
Highly stable and tunable peptoid/hemin enzymatic mimetics with natural peroxidase-like activities [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Developing tunable and stable peroxidase mimetics with high catalytic efficiency provides a promising opportunity to improve and expand enzymatic catalysis in lignin depolymerization.
- Closing excerpt
- Because Pep/hemin catalysts are highly robust and tunable, we expect that they offer tremendous opportunities for lignin valorization to high value products.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
Developing tunable and stable peroxidase mimetics with high catalytic efficiency provides a promising opportunity to improve and expand enzymatic catalysis in lignin depolymerization. A class of peptoid-based peroxidase mimetics with tunable catalytic activity and high stability is developed by constructing peptoids and hemins into self-assembled crystalline nanomaterials. By varying peptoid side chain chemistry to tailor the microenvironment of active sites, these self-assembled peptoid/hemin nanomaterials (Pep/hemin) exhibit highly modulable catalytic activities toward two lignin model substrates 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 3,3',5,5'-tetramethylbenzidine. Among them, a Pep/hemin complex containing the pyridyl side chain showed the best catalytic efficiency (Vmax/Km = 5.81 × 10-3 s-1). These Pep/hemin catalysts are highly stable; kinetics studies suggest that they follow a peroxidase-like mechanism. Moreover, they exhibit a high efficacy on depolymerization of a biorefinery lignin. Because Pep/hemin catalysts are highly robust and tunable, we expect that they offer tremendous opportunities for lignin valorization to high value products.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35641490 · DOI · PMC9156750
Mitoferrin, Cellular and Mitochondrial Iron Homeostasis [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Iron is essential for many cellular processes, but cellular iron homeostasis must be maintained to ensure the balance of cellular signaling processes and prevent disease.
- Closing excerpt
- Here, we review the discovery and structure of the mitoferrins, as well as the significance of these proteins in maintaining cytosolic and mitochondrial iron homeostasis for the prevention of cancer and many other diseases.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (139 words)
Iron is essential for many cellular processes, but cellular iron homeostasis must be maintained to ensure the balance of cellular signaling processes and prevent disease. Iron transport in and out of the cell and cellular organelles is crucial in this regard. The transport of iron into the mitochondria is particularly important, as heme and the majority of iron-sulfur clusters are synthesized in this organelle. Iron is also required for the production of mitochondrial complexes that contain these iron-sulfur clusters and heme. As the principal iron importers in the mitochondria of human cells, the mitoferrins have emerged as critical regulators of cytosolic and mitochondrial iron homeostasis. Here, we review the discovery and structure of the mitoferrins, as well as the significance of these proteins in maintaining cytosolic and mitochondrial iron homeostasis for the prevention of cancer and many other diseases.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36359860 · DOI · PMC9658796
Proteasome-guided haem signalling axis contributes to T cell exhaustion [4]
Abstract reading summary — source excerpts
- Opening excerpt
- The accumulation of depolarized mitochondria commits T cells to exhaustion1-3, yet the precise mechanism remains unclear.
- Closing excerpt
- Our findings identify a proteasome-guided haem signalling axis, governed by mitochondrial integrity, as a regulator of CD8+ T cell exhaustion and propose innovative therapeutic strategies that exploit this pathway to optimize adoptive cellular immunotherapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (175 words)
The accumulation of depolarized mitochondria commits T cells to exhaustion1-3, yet the precise mechanism remains unclear. Here we find that exhausted CD8+ T cells increase proteasome activity owing to the accumulation of depolarized mitochondria, which drives the selective degradation of mitochondrial proteins and the release of regulatory haem through haemoprotein breakdown. In turn, increased regulatory haem disrupts BACH2-mediated transcriptional regulation, thereby exacerbating T cell exhaustion and compromising stemness-like properties. Inhibition of nuclear import of regulatory haem prevents BACH2 degradation and enhances the anti-tumour efficacy of antigen-specific T cells. We find that the therapeutic efficacy of human CD19+ chimeric antigen receptor (CAR)-T cells in patients with B cell acute lymphoblastic leukaemia negatively correlates with the proteasome gene signature in their CAR-T cells. Manufacturing CAR-T cells in the presence of bortezomib, an FDA-approved proteasome inhibitor, prevents T cell exhaustion and improves therapeutic efficacy. Our findings identify a proteasome-guided haem signalling axis, governed by mitochondrial integrity, as a regulator of CD8+ T cell exhaustion and propose innovative therapeutic strategies that exploit this pathway to optimize adoptive cellular immunotherapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41851457 · DOI · PMC13658038
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Heme enzyme structure and function [5]
- Research article Macrophages and Iron Metabolism [6]
- Research article Heme Synthesis and Acquisition in Bacterial Pathogens [7]
- Research article Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product [8]
- Research article Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved [9]
- Research article Molecular Mechanisms of Iron and Heme Metabolism [10]
References
- Kalvet I, Ortmayer M, Zhao J, Crawshaw R, Ennist NM, Levy C, et al.. Design of Heme Enzymes with a Tunable Substrate Binding Pocket Adjacent to an Open Metal Coordination Site. . 2023. PMID 37341421 · DOI · PMC10326885
- Jian T, Zhou Y, Wang P, Yang W, Mu P, Zhang X, et al.. Highly stable and tunable peptoid/hemin enzymatic mimetics with natural peroxidase-like activities. . 2022. PMID 35641490 · DOI · PMC9156750
- Ali MY, Oliva CR, Flor S, Griguer CE. Mitoferrin, Cellular and Mitochondrial Iron Homeostasis. . 2022. PMID 36359860 · DOI · PMC9658796
- Xu Y, Shangguan Y, Chuang YM, Chang TH, Liu W, Peng JJ, et al.. Proteasome-guided haem signalling axis contributes to T cell exhaustion. . 2026. PMID 41851457 · DOI · PMC13658038
- Poulos TL. Heme enzyme structure and function. Chem Rev. 2014. PMID 24400737 · DOI · PMC3981943
- Soares MP, Hamza I. Macrophages and Iron Metabolism. Immunity. 2016. PMID 26982356 · DOI · PMC4794998
- Choby JE, Skaar EP. Heme Synthesis and Acquisition in Bacterial Pathogens. J Mol Biol. 2016. PMID 27019298 · DOI · PMC5125930
- Dailey HA, Dailey TA, Gerdes S, Jahn D, Jahn M, O'Brian MR, et al.. Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product. Microbiol Mol Biol Rev. 2017. PMID 28123057 · DOI · PMC5312243
- Bastide NM, Pierre FH, Corpet DE. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer Prev Res (Phila). 2011. PMID 21209396 · DOI
- Dutt S, Hamza I, Bartnikas TB. Molecular Mechanisms of Iron and Heme Metabolism. Annu Rev Nutr. 2022. PMID 35508203 · DOI · PMC9398995
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.