The structure of the enzyme that converts methemoglobin to hemoglobin[1]
Methemoglobin (British: methaemoglobin) (pronounced "met-hemoglobin") is a hemoglobin in the form of metalloprotein, in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin. Methemoglobin cannot bind oxygen, which means it cannot carry oxygen to tissues. It is bluish chocolate-brown in color. In human blood a trace amount of methemoglobin is normally produced spontaneously, but when present in excess the blood becomes abnormally dark bluish brown. The NADH-dependent enzyme methemoglobin reductase (a type of diaphorase) is responsible for converting methemoglobin back to hemoglobin.
Normally one to two percent of a person's hemoglobin is methemoglobin; a higher percentage than this can be genetic or caused by exposure to various chemicals and depending on the level can cause health problems known as methemoglobinemia. A higher level of methemoglobin will tend to cause a pulse oximeter to read closer to 85% regardless of the true level of oxygen saturation. An abnormal increase of methemoglobin will increase the oxygen binding affinity of normal hemoglobin, resulting in a decreased unloading of oxygen to the tissues. [2]
Contents
1Common causes of elevated methemoglobin
2Therapeutic uses
3Methemoglobin saturation
4Blood stains
5See also
6References
7External links
Common causes of elevated methemoglobin
Reduced cellular defense mechanisms
Children younger than 4 months exposed to various environmental agents
Pregnant women are considered vulnerable to exposure of high levels of nitrates in drinking water[3]
Cytochrome b5 reductase deficiency
G6PD deficiency
Hemoglobin M disease
Pyruvate kinase deficiency
Various pharmaceutical compounds
Local anesthetic agents, especially prilocaine and benzocaine.[4]
Some family members of the Fugate family in Kentucky, due to a recessive gene, had blue skin from an excess of methemoglobin.[6]
In cats
Ingestion of paracetamol (i.e. acetaminophen, tylenol)[7]
Therapeutic uses
Amyl nitrite is administered to treat cyanide poisoning. It works by converting hemoglobin to methemoglobin, which allows for the binding of cyanide and the formation of cyanomethemoglobin. The immediate goal of forming this cyanide adduct is to prevent the binding of free cyanide to the cytochrome a3 group in cytochrome c oxidase.[8]
Methemoglobin saturation
See also: Methemoglobinemia
Methemoglobin is expressed as a concentration or a percentage. Percentage of methemoglobin is calculated by dividing the concentration of methemoglobin by the concentration of total hemoglobin. Percentage of methemoglobin is likely a better indicator of illness severity than overall concentration, as underlying medical conditions play an important role. For example, a methemoglobin concentration of 1.5 g/dL may represent a percentage of 10% in an otherwise healthy patient with a baseline hemoglobin of 15 mg/dL, whereas the presence of the same concentration of 1.5 g/dL of methemoglobin in an anemic patient with a baseline hemoglobin of 8 g/dL would represent a percentage of 18.75%. The former patient will be left with a functional hemoglobin concentration of 13.5 g/dL and potentially remain asymptomatic while the latter patient with a functional hemoglobin concentration 6.5 g/dL may be severely symptomatic with a methemoglobin of less than 20%.[9]
1-2% Normal
Less than 10% metHb - No symptoms
10-20% metHb - Skin discoloration only (most notably on mucous membranes)
20-30% metHb - Anxiety, headache, dyspnea on exertion
This may be further compounded by the "functional hemoglobin's" decreased ability to release oxygen in the presence of methemoglobin. Anemia, congestive heart failure, chronic obstructive pulmonary disease, and essentially any pathology that impairs the ability to deliver oxygen may worsen the symptoms of methemoglobinemia.[9]
Blood stains
Increased levels of methemoglobin are found in blood stains. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO2) to methemoglobin (met-Hb) and hemichrome (HC).[10]
See also
Methemoglobinemia
Blue baby syndrome
References
^Bando, S.; Takano, T.; Yubisui, T.; Shirabe, K.; Takeshita, M.; Nakagawa, A. (2004). "Structure of human erythrocyte NADH-cytochromeb5reductase". Acta Crystallographica Section D. 60 (11): 1929–1934. doi:10.1107/S0907444904020645. PMID 15502298.
^Denshaw-Burke, Mary (2006-11-07). "Methemoglobinema". Archived from the original on 2008-04-11. Retrieved 2008-03-31.
^Manassaram, D. M.; Backer, L. C.; Messing, R.; Fleming, L. E.; Luke, B.; Monteilh, C. P. (2010). "Nitrates in drinking water and methemoglobin levels in pregnancy: A longitudinal study". Environmental Health. 9: 60. doi:10.1186/1476-069X-9-60. PMC 2967503. PMID 20946657.
^"Drug Safety and Availability - FDA Drug Safety Communication: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth". Archived from the original on 2012-04-19. Retrieved 2012-04-12.
^ abDela Cruz, Maricel; Glick, Joshua; Merker, Seth H.; Vearrier, David (11 May 2018). "Survival after severe methemoglobinemia secondary to sodium nitrate ingestion". Toxicology Communications. 2: 21–23. doi:10.1080/24734306.2018.1467532.
^"Genetics Solves Blue-Tinged Mystery". 2012-02-22. Archived from the original on 2012-03-18. Retrieved 2012-03-21.
^Dowers, Kirsty (2011-08-01). "Don't eat that! Toxicities in cats (Proceedings)". Archived from the original on 2015-09-05. Retrieved 2018-11-02.
^Vale, J. A. (2001). "Cyanide Antidotes: from Amyl Nitrite to Hydroxocobalamin - Which Antidote is Best?". Toxicology. 168 (1): 37–38.
^ abWilkerson, Richard G.; Nappe, Thomas M. (2019-05-05). This source from PubMed is licensed under the Creative Commons Attribution License. says in the Copyright and License information section of the source.. "Methemoglobinemia". NCBI Bookshelf. PMID 30726002. Retrieved 2019-05-10.
^Bremmer et al PLoS ONE 2011 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021845 Archived 2014-03-26 at the Wayback Machine
External links
Methemoglobin at the US National Library of Medicine Medical Subject Headings (MeSH)
MetHb Formation
The Blue people of Troublesome Creek
v
t
e
Proteins that contain heme (hemoproteins)
Globins
Hemoglobin
Subunits
Alpha locus on 16:
α
HBA1
HBA2
pseudo
ζ
HBZ
θ
HBQ1
μ
HBM
Beta locus on 11:
β
HBB
δ
HBD
γ
HBG1
HBG2
ε
HBE1
Tetramers
stages of development:
Embryonic
HbE Gower 1 (ζ2ε2)
HbE Gower 2 (α2ε2)
HbE Portland I (ζ2γ2)
HbE Portland II (ζ2β2)
Fetal
HbF/Fetal (α2γ2)
HbA (α2β2)
Adult
HbA (α2β2)
HbA2 (α2δ2)
HbF/Fetal (α2γ2)
pathology:
HbH (β4)
Barts (γ4)
HbS (α2βS2)
HbC (α2βC2)
HbE (α2βE2)
HbO (α2βO2)
Compounds
Carboxyhemoglobin
Carbaminohemoglobin
Oxyhemoglobin/Deoxyhemoglobin
Sulfhemoglobin
Other human
Glycated hemoglobin
Methemoglobin
Nonhuman
Chlorocruorin
Erythrocruorin
Other
human:
Myoglobin
Metmyoglobin
Neuroglobin
Cytoglobin
plant:
Leghemoglobin
Other
Cytochrome
Cytochrome b
Cytochrome P450
Methemalbumin
see also disorders of globin and globulin proteins
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… formation and reduction of methemoglobin are balanced, and the steady-state level of methemoglobin is approximately 1 percent of total hemoglobin. Formation of methemoglobin – The following processes contribute …
…lethargy. At higher methemoglobin levels, respiratory depression, altered consciousness, shock, seizures, and death may occur. Acquired methemoglobinemia is life-threatening when methemoglobin comprises more …
…per 1000 cases . Methemoglobin is an altered state of hemoglobin in which the ferrous (Fe2+) irons of heme are oxidized to the ferric (Fe3+) state. The ferric hemes of methemoglobin are unable to bind …
… Methemoglobin levels are usually kept low (typically <1 to 3 percent) by the enzymes cytochrome b5 reductase (also called diaphorase or methemoglobin reductase) and NADPH-(flavin) methemoglobin reductase …
…separately. Methemoglobinemia can be congenital (eg, cytochrome b5 reductase or cytochrome b5 deficiency, hemoglobin M disease) or acquired (usually drugs or toxins ). Methemoglobinemia should be suspected …