Congenital Methemoglobinemia with a Deficiency of Cytochrome B5

Hegesh, Emanuel; Hegesh, Julius; Kaftory, Avinoam

doi:10.1056/nejm198603203141206

Cited by 120 publications

(68 citation statements)

References 30 publications

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“…Type 3 is no longer recognized as a separate entity since it was shown [11] to be identical to type 1. Type 4 was described in a single case, and is manifested by an attenuated concentration of cytochrome b5 [12].…”

Section: Nadh-cytochrome B5 Reductasementioning

confidence: 99%

Methemoglobin—It's not just blue: A concise review

Umbreit¹

2006

American J Hematol

333

280

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Hemoglobin has functions besides carrying oxygen to the tissues, and regulates vascular tone and inflammation via a redox couple with methemoglobin. Hemoglobin has iron in the reduced valance Fe(II) and methemoglobin has iron in the oxidized valance Fe (III), with a free energy capable of producing water from oxygen. In generating methemoglobin the couple functions as a nitrite reductase. The degree of oxidation of hemoglobin senses the oxygen level in the blood and uses its ability to produce nitric oxide from nitrite to control vascular tone, increasing blood flood when the proportion of oxygenated hemoglobin falls. Additional cardiovascular damage is produced by methemoglobin mediated oxidation of light density lipoproteins, accelerating arteriosclerosis. In addition, the release of heme from methemoglobin is an important factor in inflammation. These physiologic functions are paralleled by the well-described role in the oxidation of various drugs resulting in methemoglobinemia. Am. J. Hematol. 82:134-144, 2007. V V C 2006 Wiley-Liss, Inc.

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Section: Nadh-cytochrome B5 Reductasementioning

confidence: 99%

Methemoglobin—It's not just blue: A concise review

Umbreit¹

2006

American J Hematol

333

280

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“…In the process of fatty acid desaturation it interacts with NADH-cytochrome b, reductase [2, 31, and a role of cytochrome b, as electron donor to cytochrome P-450 has been proposed [4, 51. The protein is normally membrane bound, although a soluble form is found in erythrocytes, where its physiological role is that of reducing methemoglobin [6]. The membrane-bound form may be solubilized by incubation with proteolytic enzymes, such as trypsin.…”

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confidence: 99%

Solution Structure of Reduced Microsomal Rat Cytochrome b₅

Banci

Bertini

Ferroni

et al. 1997

European Journal of Biochemistry

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The solution structure of the major form of the reduced soluble fragment of rat microsomal cytochrome b, has been solved through 'H-NMR spectroscopy. The protein contains 98 amino acids. Proton assignment was available for residues 1-94, except 90 [Guiles, R. D., Basus, V. J., Kuntz, I. D. & Waskell, L. (1992) Biochemistry 31, 11 365-11 3751 and has been confirmed. From 1722 NOES, of which 1203 were found to be meaningful, a family of 40 energy-minimized structures has been obtained with average backbone rmsd (for residues 5-89) of 0.078-tO.018 nm and average target function of 0.0045 nm', no distance violations being larger than 0.029 nm. The structure has been compared with the X-ray structure of the oxidized rat mitochondria1 isoenzyme and with that of the highly similar bovine microsomal isoenzyme in the oxidized form. The analysis of the elements of secondary structure is instructive in terms of their stability and of their occurrence in related structures, and of the capability of NMR and X-ray spectroscopy to observe them. Some detailed structural variations are noticed among the solved structures of the various isoenzymes and between solid and solution. The structural features in solution of the residues proposed to be involved in protein-protein recognition are found to be largely conserved with respect to the solid state.Keywords: cytochronie b,; protein recognition; solution structure; secondary structure.Cytochrome b, is a low-spin hemoprotein that acts as an electron-transfer mediator in numerous redox systems [I]. Different redox partners have been reported for cytochrome b, in vivo. In the process of fatty acid desaturation it interacts with NADH-cytochrome b, reductase [2, 31, and a role of cytochrome b, as electron donor to cytochrome P-450 has been proposed [4, 51. The protein is normally membrane bound, although a soluble form is found in erythrocytes, where its physiological role is that of reducing methemoglobin [6]. The membrane-bound form may be solubilized by incubation with proteolytic enzymes, such as trypsin. The soluble fragment of cytochrome b, still contains the heme and retains activity with respect to protein recognition and electron transfer [7]. It is well known that the soluble fragment of cytochrome b, interacts with cytochrome c, and that the reaction between the two is fast [7]. Such a complex has been an important model for the study of long-range biological electron transfer and, more generally, of the mechanisms of protein-protein recognition and interaction, mainly due because the crystallographic structures of the two individual components have been available since 1971 [8, 91. The interaction of cytochrome b, with cytochrome c has been studied extensively through a number of biochemical and biophysical methods [lo]. In particular, the small size of the two proteins allowed the investigation of the complex of the two through NMR spectroscopy as early as 1983 (111.The NMR investigation of cytochrome b, is significant in the frame of the current debate on the differences ...

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“…A microsomal form of cyt b 5 is required for numerous biosynthetic and biotransformation reactions, which include P450-dependent reactions (3), desaturation of fatty acids (4), plasmalogen biosynthesis (5), and cholesterol biosynthesis (6,7). A soluble form of cyt b 5 is involved in the reduction of methemoglobin in erythrocytes (8) and the biosynthesis of N-glyconeuraminic acid (9). A mitochondrial form, bound to the outer mitochondrial membrane, has been described in mammals as well (10).…”

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confidence: 99%

Molecular Cloning, Overexpression in Escherichia coli, Structural and Functional Characterization of House Fly Cytochrome b5

Guzov¹,

Houston

Murataliev³

et al. 1996

Journal of Biological Chemistry

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1 was first discovered in Cecropia silkworm larvae (1), but the functions of this membrane-bound heme protein have been most extensively studied in mammals (2, 3). A microsomal form of cyt b 5 is required for numerous biosynthetic and biotransformation reactions, which include P450-dependent reactions (3), desaturation of fatty acids (4), plasmalogen biosynthesis (5), and cholesterol biosynthesis (6, 7). A soluble form of cyt b 5 is involved in the reduction of methemoglobin in erythrocytes (8) and the biosynthesis of N-glyconeuraminic acid (9). A mitochondrial form, bound to the outer mitochondrial membrane, has been described in mammals as well (10). Cyt b 5 -like sequences are also found as part of larger polypeptides such as flavocytochrome b 2 , sulfite oxidase and nitrate reductase (11), probably as a result of gene fusion events. The role of cyt b 5 in microsomal P450-dependent monooxygenase reactions has been studied most extensively.P450s are a large superfamily of heme proteins which play a crucial role in the biosynthesis of a number of endogenous compounds (steroid hormones, vitamins D 3 , eicosanoids, and so forth) and in the activation or detoxification of a vast variety of xenobiotics. In many of these reactions, cyt b 5 is known to determine the fate of certain substrates by either stimulating (2, 3) or inhibiting (2, 12, 13) substrate metabolism, or even by influencing the type of reaction catalyzed (14). The stimulating effect of cyt b 5 has been thought to result from: 1) enhanced rate of the second electron transfer to P450 (12, 15, 16); 2) increased "coupling" of the reaction, i.e. inhibition of superoxide or hydrogen peroxide formation (2, 12, 17, 18); 3) allosteric effects (19,20); and 4) stimulation of the first electron transfer from P450 reductase to some P450s (21). However, the exact mechanism by which cyt b 5 affects P450-dependent reactions remains unclear.Insect P450s have been extensively studied because of their crucial role in the biosynthesis of hormones regulating insect growth, development, and reproduction (ecdysteroids and juvenile hormones) and in the biotransformation of foreign compounds of synthetic (insecticides) or natural (plant and microbial toxins) origin (22). Metabolism of insecticides by P450s is a major mechanism of insecticide resistance in insects (22, 23), and detoxification of plant toxins by P450s is thought to be an adaptation to the hazards of herbivory (24). Both CYP6A1, an insect P450, which is overproduced in insecticide-resistant strains of the house fly, and NADPH-dependent cytochrome P450 reductase, which provides electrons to P450s from NADPH, have been cloned from the house fly, Musca domestica (25, 26) and expressed in E. coli (27). We have found that epoxidation of the cyclodiene insecticide heptachlor by CYP6A1 is stimulated by rat microsomal cyt b 5 in a reconstituted system.2 Furthermore, immunological evidence for the involvement of cyt b 5 in several P450-dependent monooxygenase activities in house fly microsomes has been reported (28).Our...

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Congenital Methemoglobinemia with a Deficiency of Cytochrome B5

Cited by 120 publications

References 30 publications

Methemoglobin—It's not just blue: A concise review

Methemoglobin—It's not just blue: A concise review

Solution Structure of Reduced Microsomal Rat Cytochrome b₅

Molecular Cloning, Overexpression in Escherichia coli, Structural and Functional Characterization of House Fly Cytochrome b5

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Congenital Methemoglobinemia with a Deficiency of Cytochrome B5

Cited by 120 publications

References 30 publications

Methemoglobin—It's not just blue: A concise review

Methemoglobin—It's not just blue: A concise review

Solution Structure of Reduced Microsomal Rat Cytochrome b5

Molecular Cloning, Overexpression in Escherichia coli, Structural and Functional Characterization of House Fly Cytochrome b5

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Product

Resources

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Solution Structure of Reduced Microsomal Rat Cytochrome b₅