methaemoglobin

関: methemoglobin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/11 01:20:46」(JST)

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The structure of the enzyme that converts methemoglobin to hemoglobin^[1]

Methemoglobin (English: methaemoglobin) (pronounced "met-hemoglobin") is a form of the oxygen-carrying metalloprotein hemoglobin, 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, unlike oxyhemoglobin.^[2] 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 (diaphorase I) 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.^[3]

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^[4]
- Cytochrome b5 reductase deficiency
- G6PD deficiency
- Hemoglobin M disease
- Pyruvate kinase deficiency
Various pharmaceutical compounds
- Local anesthetic agents, especially prilocaine and benzocaine.^[5]
- Amyl nitrite, chloroquine, dapsone, nitrates, nitrites, nitroglycerin, nitroprusside, phenacetin, phenazopyridine, primaquine, quinones and sulfonamides
Environmental agents
- Aromatic amines (e.g. p-nitroaniline, patient case)
- Arsine
- Chlorobenzene
- Chromates
- Nitrates/nitrites
Inherited disorders
- Some family members of the Fughate 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)^{[citation needed]}

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 non-toxic cyanomethemoglobin.^[7]

Methemoglobin saturation

Methemoglobin saturation is expressed as the percentage of hemoglobin in the methemoglobin state; That is MetHb as a proportion of Hb.

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
30-50% metHb - Fatigue, confusion, dizziness, tachypnea, palpitations
50-70% metHb - Coma, seizures, arrhythmias, acidosis
Greater than 70% metHb - Death

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).^[8]

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.
^ http://www.rtso.ca/methemoglobin-causes-effects/
^ Denshaw-Burke, Mary (2006-11-07). "Methemoglobinema". 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.
^ http://www.fda.gov/Drugs/DrugSafety/ucm250024.htm
^ http://abcnews.go.com/Health/blue-skinned-people-kentucky-reveal-todays-genetic-lesson/story?id=15759819#.T2oS0HqV2So
^ Vale, J. A. (2001). "Cyanide Antidotes: from Amyl Nitrite to Hydroxocobalamin - Which Antidote is Best?". Toxicology 168 (1): 37–38.
^ Bremmer et al PloS One 2011 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021845

External links

Methemoglobin at the US National Library of Medicine Medical Subject Headings (MeSH)
MetHb Formation
The Blue people of Troublesome Creek

UpToDate Contents

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1. メトヘモグロビン血症の臨床的特徴、診断、および治療 clinical features diagnosis and treatment of methemoglobinemia
2. メトヘモグロビン血症の遺伝学および病因 genetics and pathogenesis of methemoglobinemia
3. 下肢末梢動脈疾患の症状を治療するための試験的治療 investigational therapies for treating symptoms of lower extremity peripheral artery disease
4. シアン化物中毒 cyanide poisoning
5. 動脈血液ガス arterial blood gases

English Journal

Comparative study of the effect of BPA and its selected analogues on hemoglobin oxidation, morphological alterations and hemolytic changes in human erythrocytes.

Maćczak A1, Bukowska B1, Michałowicz J2.
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.Comp Biochem Physiol C Toxicol Pharmacol.2015 Oct-Nov;176-177:62-70. doi: 10.1016/j.cbpc.2015.07.008. Epub 2015 Jul 29.
Bisphenol A (BPA) has been shown to provoke many deleterious impacts on human health, and thus it is now successively substituted by BPA analogues, whose effects have been poorly investigated. Up to now, only one study has been realized to assess the effect of BPA on human erythrocytes, which showed
PMID 26232583

Characterization of extra virgin olive oils produced with typical Italian varieties by their phenolic profile.

Del Monaco G1, Officioso A2, D'Angelo S3, La Cara F4, Ionata E1, Marcolongo L1, Squillaci G1, Maurelli L1, Morana A1.
Food chemistry.Food Chem.2015 Oct 1;184:220-8. doi: 10.1016/j.foodchem.2015.03.071. Epub 2015 Mar 26.
Evaluation of phenolic profile, antioxidant power, and protective capacity against oxidation of red blood cells (RBCs) of olive oil phenolic extracts (OOPEs) from several Italian varieties were studied. Phenolic profiles, and quantification of seven selected bioactive compounds were performed by RP-
PMID 25872448

Determination of Human Hemoglobin Derivatives.

Attia AM1, Ibrahim FA, Abd El-Latif NA, Aziz SW, Abdelmottaleb Moussa SA, Elalfy MS.
Hemoglobin.Hemoglobin.2015 Oct;39(5):371-4. doi: 10.3109/03630269.2015.1062775. Epub 2015 Jul 21.
The levels of the inactive hemoglobin (Hb) pigments [such as methemoglobin (metHb), carboxyhemoglobin (HbCO) and sulfohemoglobin (SHb)] and the active Hb [in the oxyhemoglobin (oxyHb) form] as well as the blood Hb concentration in healthy non pregnant female volunteers were determined using a newly
PMID 26193973

Japanese Journal

Contribution of Nitric Oxide to Potassium Bromate-Induced Elevation of Methaemoglobin Concentration in Mouse Blood(Toxicology)

WATANABE Satoshi,TOGASHI Shin-ichi,FUKUI Tetsuya
Biological & pharmaceutical bulletin 25(10), 1315-1319, 2002-10-01
… In potassium bromate (KBrO_3)-treated mice (1.2 mmol/kg), elevation of methaemoglobin (MetHb) concentration in blood was observed simultaneously with an elevation of the NO concentration and attenuation of glutathione peroxidase (GPx) activity. …
NAID 110003638902

In vitro光毒性評価における活性酸素種の影響

岡本祐子
環境変異原研究 23(2), 73-81, 2001-10-20
… The haemoglobin photo-oxidation assay detects haemoglobin oxidation from oxyhaemoglobin to methaemoglobin with UVA irradiation. …
NAID 110001710483