Disorders of haem metabolism: iron and the porphyrias
Martin Andrew Crook in Clinical Biochemistry & Metabolic Medicine, 2013
Abnormalities of haem metabolism are important clinically. They include the porphyrias, which are rare, and disorders involving haem iron, such as iron deficiency, which are common in clinical practice. Most body tissues synthesize haem. In bone marrow it is incorporated into haemoglobin, an iron-containing pigment that carries oxygen from the lungs to tissues, and in muscle into myoglobin, which also binds oxygen. Carboxyhaemoglobin is cherry red in colour and is formed when carbon monoxide binds to haemoglobin or displaces oxygen from oxyhaemoglobin; haemoglobin has a greater affinity for carbon monoxide than for oxygen. Methaemoglobin is haemoglobin in which iron is in the ferric form. Sulphaemoglobin is similar to methaemoglobin but contains sulphur; unlike methaemoglobin, it cannot be reconverted to haemoglobin in vivo. The human haemochromatosis protein regulates the binding of transferrin to the transferrin receptor as well as regulating hepcidin.
Introduction
Manfred Kiese in Methemoglobinemia: A Comprehensive Treatise, 2019
Heme ferro protoporphyrin, quickly autoxidizes in aqueous solution. The binding of ferro protoporphyrin to the protein globin in its hydrophobic pockets enables the ferrous iron to form a reversible compound with molecular oxygen, oxyhemoglobin, and inhibits the autoxidation of ferrous heme to ferric heme, i.e., the formation of methemoglobin or ferrihemoglobin, but it does not fully prevent the latter reaction. The term “methemoglobinemia” was used, long before the existence of “normal” ferrihemoglobin was known, to describe abnormal states with easily detectable ferrihemoglobin contents in the blood. The early spectroscopic tests for ferrihemoglobin allowed the detection of such ferrihemoglobin contents as cause cyanosis. Following the early use of the term “ferrihemoglobinemia” to designate a pathological state, ferrihemoglobinemia should be defined as elevation of the ferrihemoglobin content of blood as causes pathological symptoms such as cyanosis or tissue hypoxia, since ferrihemoglobin does not bind oxygen reversibly as ferrohemoglobin does.
Radicals
Michael B. Smith in Biochemistry, 2020
This chapter describes radical reactions in organic chemistry and radical reactions in biological systems. Cells have developed enzymes to decompose peroxides, proteins to sequester transition metals and many antioxidants to "scavenge" free radicals, to prevent free radical formation, or to limit their deleterious effects. Hydroxyl radical (HO ) is highly reactive and it is considered to be one of the more important biological radicals. The reversible binding of molecular oxygen to form oxyhemoglobin is accompanied by side reactions in which methemoglobin is formed with the attendant formation of hydroxyl radicals. Such damage has been referred as "oxidative stress." Polyunsaturated fatty acid derivatives, for example, react with radicals to form conjugated allylic radicals that react with oxygen to give alkyl hydroperoxides via hydrogen abstraction from another lipid. The two major antioxidant mechanisms are primary antioxidants that react directly with the radicals (radical scavengers), or secondary antioxidants that trap chain propagating radicals.
Methemoglobin Forming Effect of Dimethyl Trisulfide in Mice
Published in Hemoglobin, 2018
Márton Kiss, Ilona Petrikovics, David E. Thompson
Dimethyl trisulfide (DMTS) is a natural organic trisulfide that has been patented as a promising antidotal candidate against cyanide (CN). The primary mode of action of DMTS is as a sulfur donor that enables the conversion of CN to thiocyanate. Recently, it was discovered that DMTS is capable of oxidizing hemoglobin (Hb) to methemoglobin (MetHb) in vitro. The goal of these experiments was to measure the extent of DMTS-induced MetHb formation in vivo. In these experiments, intramuscular (IM) injections of formulated DMTS were administered to mice. Following the IM injection, blood was drawn and analyzed for MetHb using a rapid spectrophotometric method. Methemoglobin levels peaked in a dose-dependent manner between 20 and 30 min., and then began dropping. The highest MetHb levels measured for the 50, 100, 200 and 250 mg/kg doses of DMTS were respectively 3.28, 6.12, 9.69, and 10.76% MetHb. These experiments provide the first experimental evidence that IM administered DMTS generates MetHb in vivo and provide additional evidence for the presence of a secondary therapeutic pathway for DMTS - CN scavenging by DMTS-generated MetHb.
Measurement of the methemoglobin concentration using Raman spectroscopy
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2014
Mingzi Lu, Lian Zhao, Ying Wang, Guoxing You, Xuemei Kan, Yuhua Zhang, Ning Zhang, Bo Wang, Yan-Jun Guo, Hong Zhou
Methemoglobin concentration is an important pathophysio-logical biomarker, reflecting the oxygen-carrying and oxygen-releasing capabilities of hemoglobin (Hb). Raman spectroscopy is used to develop a novel technique for determining the methemoglobin concentration. Raman activity combined with two-dimensional correlation analysis is an attractive method for investigating Hb oxidation, exhibiting several relevant peaks in the range of 1200–1650 cm− 1. Methemoglobin concentration is estimated by measuring the intensity of Raman peaks in the ranges of 1210–1230 cm− 1 and 1340–1380 cm− 1 with 785-nm excitation. The correlation between Raman-based methemoglobin concentration estimations and the methemoglobin concentration measured using spectrophotometry was highly significant. These results suggest the potential of Raman spectroscopy as a new quantitative approach to determine the methemoglobin concentration.
Methemoglobinemia Precipitated by Benzocaine Used During Intubation
Published in Baylor University Medical Center Proceedings, 2014
Aasim Afzal, Ruth Collazo, Andrew Z. Fenves, John Schwartz
Methemoglobinemia is a rare cause of tissue hypoxia that can quickly become fatal without immediate recognition and prompt treatment. It refers to an increase in methemoglobin in the red blood cells, which can be due to genetic deficiency of the enzymes responsible for reducing hemoglobin or can develop after exposure to oxidizing agents or xenobiotics. Local anesthetics, particularly benzocaine, have long been implicated in the formation of methemoglobin. Benzocaine is used for teething pain as well as before invasive procedures such as intubation and transesophageal echocardiogram. In this case report, we describe a patient with acute appendicitis who developed severe methemoglobinemia following use of benzocaine during an emergent intubation. Our objective is to increase awareness of this rare but potentially fatal complication associated with the use of this anesthetic.
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