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. Sometimes, it is also referred to as ferrihemoglobin. 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. Etymology The word methemoglobin derives from the Ancient Greek prefix μετα- (meta-: behind, later, subsequent) and the word hemoglobin. The name hemoglobin is itself derived from the words heme and globin, each subunit of hemoglobin being a globular protein with an embedded heme group. 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 Cytochrome b5 reductase deficiency G6PD deficiency Hemoglobin M disease Pyruvate kinase deficiency Various pharmaceutical compounds Local anesthetic agents, especially prilocaine and benzocaine. 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 Umbellulone Inherited disorders Some family members of the Fugate family in Kentucky, due to a recessive gene, had blue skin from an excess of methemoglobin. In cats Ingestion of paracetamol (i.e. acetaminophen, tylenol) Therapeutic uses Amyl nitrite is administered to treat cyanide poisoning. It works by converting hemoglobin to methemoglobin, which allows for the binding of cyanide (CN–) anions by ferric (Fe3+) cations 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. Methemoglobin saturation Methemoglobin is expressed as a concentration or a percentage. Percentage of methemoglobin is calculated by