Editing Heme (section)

==In health and disease==
Under [[homeostasis]], the reactivity of heme is controlled by its insertion into the "heme pockets" of hemoproteins.{{Citation needed|date=December 2016}} Under oxidative stress however, some hemoproteins, e.g. hemoglobin, can release their heme prosthetic groups.<ref>{{cite journal|last1 = Bunn|first1 = H. F.|last2 = Jandl|first2 = J. H.|date = Sep 1966|title = Exchange of heme among hemoglobin molecules|journal = Proc. Natl. Acad. Sci. USA|volume = 56|issue = 3|pages = 974–978|pmid = 5230192|doi = 10.1073/pnas.56.3.974|pmc=219955|bibcode = 1966PNAS...56..974B|doi-access = free}}</ref><ref>{{cite journal|last1 = Smith|first1 = M. L.|last2 = Paul|first2 = J.|last3 = Ohlsson|first3 = P. I.|last4 = Hjortsberg|first4 = K.|last5 = Paul|first5 = K. G.|date = Feb 1991|title = Heme-protein fission under nondenaturing conditions|journal = Proc. Natl. Acad. Sci. USA|volume = 88|issue = 3|pages = 882–886|pmid = 1846966|doi=10.1073/pnas.88.3.882|bibcode = 1991PNAS...88..882S|pmc=50918|doi-access = free}}</ref> The non-protein-bound (free) heme produced in this manner becomes highly cytotoxic, most probably due to the iron atom contained within its protoporphyrin IX ring, which can act as a [[Fenton's reagent]] to catalyze in an unfettered manner the production of free radicals.<ref>{{cite journal|last1=Everse|first1=J.|first2=N.|last2=Hsia|title = The toxicities of native and modified hemoglobins|journal = Free Radical Biology and Medicine|volume = 22|issue = 6|pages = 1075–1099|date=1197|pmid = 9034247|doi = 10.1016/S0891-5849(96)00499-6}}</ref> It catalyzes the oxidation and aggregation of protein, the formation of cytotoxic lipid peroxide via lipid peroxidation and damages DNA through oxidative stress. Due to its lipophilic properties, it impairs lipid bilayers in organelles such as mitochondria and nuclei.<ref>{{cite journal|last1=Kumar|first1=Sanjay|last2=Bandyopadhyay|first2=Uday|title=Free heme toxicity and its detoxification systems in humans|journal=Toxicology Letters|date=July 2005|volume=157|issue=3|pages=175–188|doi=10.1016/j.toxlet.2005.03.004|pmid=15917143}}</ref> These properties of free heme can sensitize a variety of cell types to undergo [[programmed cell death]] in response to pro-inflammatory agonists, a deleterious effect that plays an important role in the pathogenesis of certain inflammatory diseases such as [[malaria]]<ref name="pmid17496899">{{cite journal|last1=Pamplona|first1=A.|last2=Ferreira|first2=A.|last3=Balla|first3=J.|last4=Jeney|first4=V.|last5=Balla|first5=G.|last6=Epiphanio|first6=S.|last7=Chora|first7=A.|last8=Rodrigues|first8=C. D.|last9=Gregoire|first9=I. P.|last10=Cunha-Rodrigues|first10=M.|last11=Portugal|first11=S.|last12=Soares|first12=M. P.|last13=Mota|first13=M. M.|title = Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria|journal = Nature Medicine|volume = 13|issue = 6|pages = 703–710|date=Jun 2007|pmid = 17496899|doi = 10.1038/nm1586|s2cid=20675040}}</ref> and [[sepsis]].<ref>{{Cite journal
|pmid = 20881280
|year = 2010
|last1 = Larsen
|first1 = R.
|title = A central role for free heme in the pathogenesis of severe sepsis
|journal = Science Translational Medicine
|volume = 2
|issue = 51
|pages = 51ra71
|last2 = Gozzelino
|first2 = R.
|last3 = Jeney
|first3 = V.
|last4 = Tokaji
|first4 = L.
|last5 = Bozza
|first5 = F. A.
|last6 = Japiassú
|first6 = A. M.
|last7 = Bonaparte
|first7 = D.
|last8 = Cavalcante
|first8 = M. M.
|last9 = Chora
|first9 = A.
|last10 = Ferreira
|first10 = A.
|last11 = Marguti
|first11 = I.
|last12 = Cardoso
|first12 = S.
|last13 = Sepúlveda
|first13 = N.
|last14 = Smith
|first14 = A.
|last15 = Soares
|first15 = M. P.
|doi = 10.1126/scitranslmed.3001118
|s2cid = 423446
|url = https://www.arca.fiocruz.br/handle/icict/38710
}}</ref>

===Cancer===
There is an association between high intake of heme iron sourced from meat and increased risk of [[colorectal cancer]] via [[nitrosamine formation during digestion]] (N-nitroso).<ref>{{Cite journal |last1=Bastide |first1=Nadia M. |last2=Pierre |first2=Fabrice H. F. |last3=Corpet |first3=Denis E. |date=Feb 2011 |title=Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved |url=https://pubmed.ncbi.nlm.nih.gov/21209396/ |journal=Cancer Prevention Research (Philadelphia, Pa.) |volume=4 |issue=2 |pages=177–184 |doi=10.1158/1940-6207.CAPR-10-0113 |issn=1940-6215 |pmid=21209396}}</ref>

The [[American Institute for Cancer Research]] (AICR) and World Cancer Research Fund International (WCRF) concluded in a 2018 report that there is limited but suggestive evidence that foods containing heme iron increase risk of colorectal cancer.<ref>[https://www.wcrf.org/wp-content/uploads/2021/02/Colorectal-cancer-report.pdf "Diet, nutrition, physical activity and colorectal cancer"]. wcrf.org. Retrieved 12 February 2022.</ref> A 2019 review found that heme iron intake is associated with increased [[breast cancer]] risk.<ref>{{cite journal|author=Chang, Vicky C; Cotterchio, Michelle; Khoo, Edwin|year=2019|title=Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis|journal=[[BMC Cancer]]|volume=19|issue=1|pages=543|doi=10.1186/s12885-019-5642-0|pmid=31170936|pmc=6555759|doi-access=free}}</ref>