681:
methemoglobin reductase, catalyzed by leukcomethylene, to reduce methemoglobin to hemoglobin. Therefore, when methemoglobin levels are high in a patient, additional methylene blue can be introduced to be reduced to leukcomethylene to now catalyze the reduction of excess methemoglobin to hemoglobin. While the addition of methylene blue to treat cases of methemoglobinemia has been scientifically tested and proven, there are some side effects to note and monitor with high dosages of the antidote. Minor side effects include green or blue discoloration of urine; however, significant side effects include worsening of the present methemoglobinemia. Because methylene blue is an oxidizing agent itself, when it is not effectively reduced, NADPH will not be properly restored in the cell for electron transfer, resulting in increased levels of non reduced methemoglobin to support methemoglobinemia in patients. Additional studies have found that the use of methylene blue during pregnancy is associated with a high risk of small intestinal atresia, which can be fatal to the fetus.
484:
572:, red blood cells, the c5br enzyme is responsible for the recycling and conversion of methemoglobin to hemoglobin. Methemoglobin is an oxidized form of hemoglobin attached to a ferric-state iron (Fe3+), which can therefore not carry and deliver oxygen to tissues. The formation of methemoglobin occurs when electrons are not returned to the iron of a normal state hemoglobin, which is not preferred for a functioning organism. Methemoglobin is not favorable for a functional organism since oxygen needs to constantly be transferred; therefore, the soluble isoform of c5br is essential to keep levels of methemoglobin low in humans.
725:
the drug tetrahydroindenoindole was used to activate cytochrome b5 reductase activity, and observations concluded that the increased function of cb5r extended the fly's lifespan. The increased expression of cytochrome b5 reductase in mice resulted in high levels of long-chain polyunsaturated fatty acids, improved mitochondrial function, and a decrease in oxidative damage, indicating improved metabolic pathways with high levels of cb5r activity. These results indicate that cytochrome b5 reductase is a new target for new research and development of lipid metabolism and health in living organisms.
42:
428:
2506:
721:. The results showed that c5br not only increases oxygen supply and transport in a wild-type organism but also regulates the erythropoietin response to ischemic stroke. These findings have made cytochrome b5 reductase a target for future research on managing stroke risk and providing selective advantage for those with genetic disorders such as sickle cell disease.
644:
cells. With even lower levels of hemoglobin present in the body, oxygen is not able to be properly carried, which results in even more detrimental symptoms, including neurological problems and impaired biosynthesis. Effected biosynthesis in organisms can be seen by impaired fatty acid formation, which reduces the production of
648:
in nerve cells. Defected nerve cells lead to a loss of motor function and movement disorders, which are highly associated with Type II MHb. The type II variation of methemoglobinemia is the second, and more severe category of congenital disorders resulting from mutations in the c5br gene. However, it
643:
mutation where the NADH cytochrome b5 reductase enzyme is deficient in various tissues besides RBCs. This mutation typically results in the complete loss of cytochrome b5 reductase activity throughout the body, which ultimately leads to an even bigger increase in methemoglobin levels within red blood
491:
In living organisms, because methemoglobin (MetHb) is unable to bind oxygen, it must be reduced to hemoglobin (Hb) through the action of the soluble isoform of cytochrome b5 reductase. Overall, the mechanics of this reaction include electron transfer through oxidation steps, which can be accomplished
516:
to NADP+ by NAPHD methemoglobin reductase. TPNH is the most favorable pyridine nucleotide to reduce methemoglobin; however, other cofactors can be used, including leukomethylene blue. Additional reduced nucleotide pyridines can also catalyze the oxidation of hemoglobin to methemoglobin. For example,
463:
The features of cytochrome b5 reductase enzymes allow the successful reduction of molecules of cytochrome b5 to be used for various functions across the electron transport chain and metabolism. In metabolism, c5br is active in lipid conversion involving the elongation and desaturation of fatty acids
709:
Cytochrome b5 reductase is a prevalent topic in research and clinical tests to understand the additional functions of the enzyme in other metabolic pathways in the body. Mice and flies are common model organisms used to test for the relationship of cytochrome b5 reductase with the overall health of
724:
Another study with mice as well as flies tested the physiological role of cytochrome b5 reductase on lipid metabolism, health, and aging. By activating the cb5r-expressing gene in both model organisms, it was observed that lifespan and lipid metabolism were positively affected. In the model flies,
542:
The membrane-bound isoform of cytochrome b5 reductase is found in all cell types and is not limited to red blood cells. It is typically found embedded in the membranes of various cellular compartments, with a domain inserted into the lipid bilayer on the outer leaflet of the endoplasmic reticulum.
624:
mutation where the NADH cytochrome b5 reductase enzyme is not present only in the red blood cells. The lack of this enzyme results in the inability to conformationally change ferric iron to ferrous iron, which leads to an increase in methemoglobin in the cells and a decrease in hemoglobin. The
551:
of 24 residues that anchors the protein to the membrane. There is a subsequent soluble domain that is part of this isoform that attaches to the cytosol. Due to its structure and location, the membrane-bound isoform of c5br is essential for biological functions within organisms. By possessing a
680:
Most cases of methemoglobinemia are treatable and not chronic. The most common and successful treatment used to treat patients with high levels of methemoglobinemia is the antidote methylene blue. Methylene blue is already recognized as a product of the reversible reaction fueled by NAPHD
697:, can be considered. However, no additional antidote has been tested and confirmed to the extent of methylene blue, and in most cases, additional antidotes are generally ineffective. It is also noted that high doses of ascorbic acid are associated with increased urinary excretion of
670:
mutation where the NADH cytochrome b5 reductase enzyme is not present only in the red blood cells, similar to the type I MHb deficiency. Mechanisms and reactions are also similar to a type I mutation, but variants of this mutation can subsequently develop into chronic
663:
mutation where NADH cytochrome b5 reductase enzyme deficiency has an effect on all blood cells, including white blood cells and platelets in addition to red blood cells. Characteristic symptoms with this mutation are only found to be common cyanosis due to lack of
414:
Cytochrome reductase enzymes are therefore an essential component of the electron transport chain that carry out the function of cytochrome proteins and activate their reactions. Cytochrome b5 reductase successfully catalyzes the electron transfer of
496:. One mechanism, which is also the most naturally present pathway, involves electron transfer catalyzed by cytochrome b5 reductase through the oxidation of NADH to NAD+. The electron donor, NADH, that supports this reaction is a product of
431:
3-D structure of a cytochrome b5 reductase model with a ribon display and enzyme cofactor domains for NADH and FAD. The image was produced using BIOVIA Discovery Studio
Visualizer, collected for the Journal of Veterinary Internal
616:
Mutations in cytochrome b5 reductase can lead to many disorders, including autosomal recessive congenital methemoglobinemia. There are over 65 mutations of the enzyme that can lead to various types of the disorder. Some include:
898:
Luyo-Acero GE, Uezato H, Oshiro M, Takei K, Kariya K, Katakura K, et al. (May 2004). "Sequence variation of the cytochrome b gene of various human infecting members of the genus
Leishmania and their phylogeny".
684:
It is recommended that treatment with methylene blue requires two doses before being deemed ineffective. If symptoms of methemoglobinemia are still present after the second dosage, alternative treatments, including
625:
decrease in available hemoglobin results in reduced amounts of oxygen across the body. Due to the lack of oxygen that can be carried by the RBCs, symptoms include a bluish appearance of the skin, lips, and nails (
864:
Wallace DC, Lott MT, Procaccio V (May 2013). "Mitochondrial medicine: the mitochondrial biology and genetics of metabolic and degenerative diseases, cancer, and aging.". In Rimoin D, Pyeritz R, Korf B (eds.).
504:. The reduction reaction converts the oxidized methemoglobin to the reduced hemoglobin form, that now has an affinity for oxygen. Another mechanism involves the conversion of the reduced pyridine nucleotide
1675:
Kidd SA, Lancaster PA, Anderson JC, Boogert A, Fisher CC, Robertson R, et al. (January 1996). "Fetal death after exposure to methylene blue dye during mid-trimester amniocentesis in twin pregnancy".
745:
Tamura M, Yubisui T, Takeshita M, Kawabata S, Miyata T, Iwanaga S (May 1987). "Structural comparison of bovine erythrocyte, brain, and liver NADH-cytochrome b5 reductase by HPLC mapping".
552:
membrane binding domain and a water-soluble domain, this isoform is able to carry out chemical and redox reactions for the electron transport chain and is functional in the formation of
1713:"Phenazopyridine-Induced Methemoglobinemia in a Jehovah's Witness Treated with High-Dose Ascorbic Acid Due to Methylene Blue Contradictions: A Case Report and Review of the Literature"
637:
disorders resulting from mutations of the c5br gene. While this is the most common mutation, the symptoms are less severe, and life expectancy is, for the most part, unaffected.
310:
In its b5-reducing capacity, this enzyme is involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, and drug metabolism. This enzyme can also reduce
448:, in order to biochemically connect the complex. Once cytochrome b5 reductase catalyzes electron transfer, the resulting reduced form of cytochrome b5 reduces the oxidized
517:
in the reverse reaction of NAPHD methemoglobin reductase, methylene blue can be used to catalyze the oxidation of hemoglobin to methemoglobin. Other enzymes, including
228:
384:. Cytochromes are categorized into three classes (a,b, and c) in accordance with the type of heme that is present in the core and their light-absorption spectra.
1962:
713:
A recent study from 2023 used mice as a model to test the extended effects of c5br on oxygen supply in the presence of additional oxidative stress, such as from
2137:
1764:"Abstract 104: Cytochrome B5 Reductase 3 Regulates The Erythropoietin Response To Ischemic Stroke in a Mouse Model of Chronic Anemia And Oxidative Stress"
467:
Specialized isoforms of the enzyme c5br are heavily functional in the blood to help deliver oxygen to the body's tissue by conformationally changing
2160:
1066:
Bewley MC, Marohnic CC, Barber MJ (November 2001). "The structure and biochemistry of NADH-dependent cytochrome b5 reductase are now consistent".
780:
Elahian F, Sepehrizadeh Z, Moghimi B, Mirzaei SA (June 2014). "Human cytochrome b5 reductase: structure, function, and potential applications".
2035:
247:
1992:
2000:
1979:
1955:
1791:
1337:
2017:
399:
instead of on the outer portion, and this particular class has high sequence variation. With the ability to express approximately 1080
2076:
1689:
2183:
1244:
629:). This is the most common variation of a c5br mutation. The type I variation of methemoglobinemia is the first category out of two
1391:
Benz EJ, Ebert BL (2018). "Hemoglobin
Variants Associated With Hemolytic Anemia, Altered Oxygen Affinity, and Methemoglobinemias".
2008:
1830:
17:
240:
1948:
475:. Other isoforms are useful in chemical reactions throughout the body, with assistance in the breakdown of various substances.
444:
binding domain complex for NADH and a FAD-binding domain. A three-stranded linker domain is present, as well as water-mediated
1616:
1408:
1375:
1220:
882:
191:
1654:
1519:
1461:
1432:
1179:
1490:
1904:
2225:
2061:
1996:
1975:
351:
483:
2173:
2052:
493:
350:, a soluble form and a membrane-bound form. This enzyme is involved in the transfer of reducing equivalents from
1889:
185:
167:
2381:
2108:
2103:
2098:
817:"Cytochrome b5 and NADH cytochrome b5 reductase: genotype-phenotype correlations for hydroxylamine reduction"
505:
172:
2192:
522:
396:
1823:
1015:"Clinical, metabolic, and genetic characterization of hereditary methemoglobinemia caused by cytochrome b
649:
was found that the mutation is specific and more prominent in specific populations, including
Athabasca,
288:
54:
252:
2496:
1358:
Otto CN (January 2020). "Chapter 7: Hemoglobin metabolism". In
Keohane EM, Otto CN, Walenga JN (eds.).
526:
497:
487:
Oxidation and reduction pathways of methemoglobin and hemoglobin. Published by N. De Crem et al., 2022.
408:
160:
2482:
2469:
2456:
2443:
2430:
2417:
2404:
2366:
2056:
1869:
1864:
694:
95:
1013:
Jaffey JA, Reading NS, Giger U, Abdulmalik O, Buckley RM, Johnstone S, et al. (November 2019).
2376:
2330:
2273:
1983:
596:, NADH-cytochrome b5 reductase 3, located on chromosome 22q13.2 with 12 exons that encode for c5br.
377:
78:
1106:
Martin-Montalvo A, Sun Y, Diaz-Ruiz A, Ali A, Gutierrez V, Palacios HH, et al. (2016-05-12).
602:, NADH-cytochrome b5 reductase 4, located on chromosome 6q14.2 with 16 exons that encode for c5br.
590:, NADH-cytochrome b5 reductase 2, located on chromosome 11p15.4 wit 12 exons that encode for c5br.
188:
2278:
2066:
1884:
584:, NADH-cytochrome b5 reductase 1, located on chromosome 1q32.1 with 9 exons that encode for c5br.
112:
1859:
1816:
2299:
2218:
1929:
1854:
1763:
366:. The overall reduction reaction from cytochrome b5 reductase aids in the control of iron in
1315:
568:
The soluble isoform of cytochrome b5 reductase is found only present in red blood cells. On
387:
The specialized protein cytochrome b5 is a class B cytochrome with a high and low potential
2371:
957:
Reductase
Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome
690:
416:
363:
1940:
1762:
Wood KC, Yuan S, Schmidt H, Hahn S, Ghosh S, Ofori-Acquah S, et al. (February 2023).
758:
148:
8:
2335:
1236:
714:
634:
544:
90:
1739:
1712:
124:
2268:
2150:
1909:
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1400:
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1291:
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1141:
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1043:
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990:
942:
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816:
83:
203:
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1924:
1919:
1783:
1744:
1693:
1646:
1612:
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1404:
1371:
1296:
1216:
1146:
1083:
1048:
995:
916:
878:
846:
797:
762:
179:
59:
941:
Gutiérrez-Merino C, Martínez-Costa OH, Monsalve M, Samhan-Arias AK (December 2021).
427:
41:
2314:
2309:
2283:
2211:
1775:
1734:
1724:
1685:
1604:
1566:
1556:
1396:
1363:
1327:
1286:
1278:
1208:
1136:
1128:
1075:
1038:
1030:
985:
975:
908:
870:
836:
828:
789:
754:
940:
2361:
2345:
2258:
832:
793:
718:
548:
347:
1511:
1453:
1424:
1171:
207:
2510:
2399:
2340:
2125:
2120:
1971:
1779:
1729:
1638:
1482:
1282:
509:
437:
367:
223:
50:
46:
1512:"CYB5R4 cytochrome b5 reductase 4 - NIH Genetic Testing Registry (GTR) - NCBI"
1483:"CYB5R3 cytochrome b5 reductase 3 - NIH Genetic Testing Registry (GTR) - NCBI"
1454:"CYB5R2 cytochrome b5 reductase 2 - NIH Genetic Testing Registry (GTR) - NCBI"
1425:"CYB5R1 cytochrome b5 reductase 1 - NIH Genetic Testing Registry (GTR) - NCBI"
912:
2520:
2304:
2263:
2088:
1914:
1787:
1332:
686:
468:
445:
355:
311:
198:
1316:"Methemoglobinemia in two infants brought to pediatric emergency department"
455:
Mechanism: NADH + H + 2 ferricytochrome b5 -> NAD + 2 ferrocytochrome b5
2253:
1874:
1843:
1748:
1650:
1580:
1300:
1267:"Once in a blue moon: Primaquine-induced methemoglobinemia - A case report"
1150:
1087:
1052:
999:
920:
850:
801:
569:
392:
343:
287:
that converts ferricytochrome from a Fe3+ form to a Fe2+ form. It contains
1697:
1132:
766:
362:
of the electron transport chain, which results in the two isoforms due to
2477:
2412:
2248:
1808:
1561:
980:
557:
419:
to then activate cytochrome b for it to carry out its role in organisms.
395:
class is especially unique because it is attached to proteins within the
359:
323:
1690:
10.1002/(SICI)1097-0223(199601)16:1<39::AID-PD789>3.0.CO;2-P
1894:
1034:
630:
553:
518:
501:
472:
449:
441:
373:
315:
136:
1079:
403:, cytochrome b proteins are commonly studied to analyze mitochondrial
63:
2451:
2425:
400:
381:
342:
Cytochrome b5 reductase (c5br) is a NADH-dependent enzyme known as a
492:
through a couple of different mechanisms involving the reduction of
2505:
2164:
626:
2141:
1839:
779:
698:
654:
376:
are redox proteins that are essential for energy transfer in the
155:
512:, which is induced by the electron transfer in the oxidation of
2464:
2234:
2080:
650:
645:
599:
593:
587:
581:
388:
284:
235:
131:
119:
107:
1105:
744:
2438:
1711:
Menakuru SR, Dhillon VS, Atta M, Mann K, Salih A (May 2023).
1542:
1362:(Sixth ed.). St. Louis (MO): Elsevier. pp. 91–103.
1117:
reductase and the control of lipid metabolism and healthspan"
513:
1674:
1012:
2093:
2039:
1970:
897:
478:
280:
143:
2203:
1543:
Paudel S, Adhikari N, Mandal S, Srivatana P (April 2022).
1313:
869:(Sixth ed.). Oxford: Academic Press. pp. 1–153.
1264:
404:
1599:
Subbiah S, Silberstein PT (2014). "Methemoglobinemia☆".
529:
in order to replenish methemoglobin levels in the cell.
346:
that results in the chemical reduction to two different
1710:
1545:"A Case of Congenital Methemoglobinemia: Rare but Real"
1166:
1164:
1162:
1160:
936:
934:
932:
930:
1101:
1099:
1097:
543:
This specific isoform is made up of approximately 300
436:
The cytochrome b5 reductase enzyme contains a typical
2494:
1636:
1157:
1065:
927:
863:
1761:
1094:
370:, which dictates the amount of oxygen cells carry.
1598:
1314:Pala A, Erkun O, Özdemir Ö, Şehmusoğlu Z (2020).
1265:De Crem N, Verleden GM, Godinas L, Vos R (2022).
391:attached to the central iron on the protein. The
2518:
1645:. Treasure Island (FL): StatPearls Publishing.
1594:
1592:
1590:
1632:
1630:
1628:
1538:
1536:
1198:
1196:
814:
2219:
1956:
1824:
867:Emery and Rimoin's Essential Medical Genetics
740:
738:
1587:
560:, and the breakdown of molecules and drugs.
1625:
1533:
1193:
968:International Journal of Molecular Sciences
2226:
2212:
1963:
1949:
1838:
1831:
1817:
1637:Ludlow JT, Wilkerson RG, Nappe TM (2024).
735:
264:
40:
1738:
1728:
1570:
1560:
1390:
1331:
1290:
1205:Clinical Biochemistry of Domestic Animals
1140:
1042:
989:
979:
840:
606:
482:
479:Reduction of methemoglobin to hemoglobin
426:
1601:Reference Module in Biomedical Sciences
1023:Journal of Veterinary Internal Medicine
815:Sacco JC, Trepanier LA (January 2010).
326:(CYB5R1, CYB5R3) perform this function
14:
2519:
1202:
2207:
1944:
1812:
1203:Harvey JW (2008). "The Erythrocyte".
759:10.1093/oxfordjournals.jbchem.a121979
380:with the help of an enzyme such as a
1357:
1320:Southern Clinics of Istanbul Eurasia
657:native populations across the world.
354:due to the FAD electron acceptor in
330:. Ferricyanide is another substrate
318:, gaining it the inaccurate synonym
1905:Methylenetetrahydrofolate reductase
1121:npj Aging and Mechanisms of Disease
943:"Structural Features of Cytochrome
452:of hemoglobin from Fe 3+ to Fe 2+.
24:
1609:10.1016/b978-0-12-801238-3.05142-4
1401:10.1016/b978-0-323-35762-3.00043-3
1368:10.1016/b978-0-323-53045-3.00016-7
1213:10.1016/b978-0-12-370491-7.00007-6
875:10.1016/b978-0-12-383834-6.00013-6
25:
2538:
1271:Respiratory Medicine Case Reports
782:Critical Reviews in Biotechnology
537:
2504:
2174:Trimethylamine-N-oxide reductase
1794:from the original on 2024-04-22
1755:
1704:
1668:
1657:from the original on 2023-01-30
1522:from the original on 2024-03-24
1504:
1493:from the original on 2024-03-24
1475:
1464:from the original on 2024-03-24
1446:
1435:from the original on 2024-03-24
1417:
1384:
1351:
1340:from the original on 2021-02-25
1307:
1258:
1247:from the original on 2023-09-24
1229:
1182:from the original on 2024-03-24
337:
1890:Dihydrolipoamide dehydrogenase
1395:. Elsevier. pp. 608–615.
1207:. Elsevier. pp. 173–240.
1059:
1006:
891:
857:
808:
773:
621:Type I methemoglobinemia (MHb)
464:and cholesterol biosynthesis.
13:
1:
2109:Neutrophil cytosolic factor 4
2104:Neutrophil cytosolic factor 2
2099:Neutrophil cytosolic factor 1
2062:NADPH—cytochrome-c2 reductase
1019:reductase deficiency in cats"
821:Pharmacogenetics and Genomics
728:
675:
521:enzymes, can convert reduced
506:triphosphopyridine nucleotide
294:NADH + H + 2 ferricytochrome
53:methemoglobin reductase with
2193:NADH dehydrogenase (quinone)
833:10.1097/FPC.0b013e3283343296
794:10.3109/07388551.2012.732031
611:
523:diphosphopyridine nucleotide
422:
397:inner mitochondrial membrane
291:and catalyzes the reaction:
7:
2233:
2053:NADPH—hemoprotein reductase
704:
532:
458:
10:
2543:
1780:10.1161/str.54.suppl_1.104
1730:10.3390/hematolrep15020034
1283:10.1016/j.rmcr.2022.101675
563:
527:glyceraldehyde-3-phosphate
409:phylogenetic relationships
301:= NAD + 2 ferrocytochrome
2390:
2382:Michaelis–Menten kinetics
2354:
2323:
2292:
2241:
2182:
2159:
2136:
2075:
2057:Cytochrome P450 reductase
2034:
2018:NAD(P) transhydrogenase (
2009:NAD(P) transhydrogenase (
1991:
1870:Butyryl CoA dehydrogenase
1865:Apoptosis-inducing factor
1850:
913:10.1017/S0031182004004792
695:hyperbaric oxygen therapy
246:
234:
222:
217:
213:
197:
178:
166:
154:
142:
130:
118:
106:
101:
89:
77:
72:
39:
34:
2274:Diffusion-limited enzyme
1333:10.14744/scie.2020.16362
575:
378:electron transport chain
322:. Isoforms expressed in
2067:Leghemoglobin reductase
2048:Methemoglobin reductase
1900:Methemoglobin reductase
1885:Cytokinin dehydrogenase
1880:Cytochrome b5 reductase
747:Journal of Biochemistry
320:methemoglobin reductase
265:Cytochrome b5 Reductase
35:cytochrome-b5 reductase
18:Methemoglobin reductase
1860:Acyl CoA dehydrogenase
488:
433:
2367:Eadie–Hofstee diagram
2300:Allosteric regulation
1930:Thioredoxin reductase
1855:Acetolactate synthase
1133:10.1038/npjamd.2016.6
607:Clinical significance
486:
430:
2377:Lineweaver–Burk plot
1562:10.7759/cureus.24152
1241:acutecaretesting.org
1176:MedlinePlus Genetics
981:10.3390/ijms23010118
691:exchange transfusion
494:pyridine nucleotides
417:reducing equivalents
364:alternative splicing
1639:"Methemoglobinemia"
1074:(45): 13574–13582.
715:sickle cell disease
701:and renal failure.
635:autosomal recessive
556:, the formation of
545:amino acid residues
2336:Enzyme superfamily
2269:Enzyme promiscuity
2151:NADH dehydrogenase
1910:NADH dehydrogenase
1717:Hematology Reports
1678:Prenatal Diagnosis
1360:Rodak's Hematology
1035:10.1111/jvim.15637
710:living organisms.
489:
434:
411:across evolution.
2492:
2491:
2201:
2200:
1938:
1937:
1925:Sarcosine oxidase
1920:Nitrate reductase
1618:978-0-12-801238-3
1410:978-0-323-35762-3
1377:978-0-323-53045-3
1222:978-0-12-370491-7
1080:10.1021/bi0106336
907:(Pt 5): 483–491.
884:978-0-12-383834-6
498:glucose oxidation
440:structure with a
262:
261:
258:
257:
161:metabolic pathway
16:(Redirected from
2534:
2509:
2508:
2500:
2372:Hanes–Woolf plot
2315:Enzyme activator
2310:Enzyme inhibitor
2284:Enzyme catalysis
2228:
2221:
2214:
2205:
2204:
1965:
1958:
1951:
1942:
1941:
1833:
1826:
1819:
1810:
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1803:
1802:
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1701:
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1584:
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1564:
1540:
1531:
1530:
1528:
1527:
1516:ncbi.nlm.nih.gov
1508:
1502:
1501:
1499:
1498:
1487:ncbi.nlm.nih.gov
1479:
1473:
1472:
1470:
1469:
1458:ncbi.nlm.nih.gov
1450:
1444:
1443:
1441:
1440:
1429:ncbi.nlm.nih.gov
1421:
1415:
1414:
1388:
1382:
1381:
1355:
1349:
1348:
1346:
1345:
1335:
1311:
1305:
1304:
1294:
1262:
1256:
1255:
1253:
1252:
1233:
1227:
1226:
1200:
1191:
1190:
1188:
1187:
1168:
1155:
1154:
1144:
1103:
1092:
1091:
1063:
1057:
1056:
1046:
1029:(6): 2725–2731.
1010:
1004:
1003:
993:
983:
938:
925:
924:
895:
889:
888:
861:
855:
854:
844:
812:
806:
805:
777:
771:
770:
753:(5): 1147–1159.
742:
215:
214:
66:
44:
32:
31:
27:Class of enzymes
21:
2542:
2541:
2537:
2536:
2535:
2533:
2532:
2531:
2517:
2516:
2515:
2503:
2495:
2493:
2488:
2400:Oxidoreductases
2386:
2362:Enzyme kinetics
2350:
2346:List of enzymes
2319:
2288:
2259:Catalytic triad
2237:
2232:
2202:
2197:
2178:
2155:
2132:
2071:
2030:
1987:
1972:Oxidoreductases
1969:
1939:
1934:
1846:
1837:
1807:
1806:
1797:
1795:
1760:
1756:
1709:
1705:
1673:
1669:
1660:
1658:
1635:
1626:
1619:
1597:
1588:
1541:
1534:
1525:
1523:
1510:
1509:
1505:
1496:
1494:
1481:
1480:
1476:
1467:
1465:
1452:
1451:
1447:
1438:
1436:
1423:
1422:
1418:
1411:
1389:
1385:
1378:
1356:
1352:
1343:
1341:
1312:
1308:
1263:
1259:
1250:
1248:
1237:"Methemoglobin"
1235:
1234:
1230:
1223:
1201:
1194:
1185:
1183:
1170:
1169:
1158:
1116:
1104:
1095:
1064:
1060:
1018:
1011:
1007:
963:
956:
949:
939:
928:
896:
892:
885:
862:
858:
813:
809:
778:
774:
743:
736:
731:
719:ischemic stroke
707:
678:
614:
609:
578:
566:
549:N-terminal tail
540:
535:
481:
461:
425:
368:red blood cells
340:
308:
307:
300:
276:
267:
68:
58:
28:
23:
22:
15:
12:
11:
5:
2540:
2530:
2529:
2514:
2513:
2490:
2489:
2487:
2486:
2473:
2460:
2447:
2434:
2421:
2408:
2394:
2392:
2388:
2387:
2385:
2384:
2379:
2374:
2369:
2364:
2358:
2356:
2352:
2351:
2349:
2348:
2343:
2338:
2333:
2327:
2325:
2324:Classification
2321:
2320:
2318:
2317:
2312:
2307:
2302:
2296:
2294:
2290:
2289:
2287:
2286:
2281:
2276:
2271:
2266:
2261:
2256:
2251:
2245:
2243:
2239:
2238:
2231:
2230:
2223:
2216:
2208:
2199:
2198:
2196:
2195:
2189:
2187:
2180:
2179:
2177:
2176:
2170:
2168:
2157:
2156:
2154:
2153:
2147:
2145:
2134:
2133:
2131:
2130:
2129:
2128:
2126:Dual oxidase 2
2123:
2121:Dual oxidase 1
2113:
2112:
2111:
2106:
2101:
2096:
2085:
2083:
2073:
2072:
2070:
2069:
2064:
2059:
2050:
2044:
2042:
2032:
2031:
2029:
2028:
2015:
2005:
2003:
1989:
1988:
1968:
1967:
1960:
1953:
1945:
1936:
1935:
1933:
1932:
1927:
1922:
1917:
1912:
1907:
1902:
1897:
1892:
1887:
1882:
1877:
1872:
1867:
1862:
1857:
1851:
1848:
1847:
1836:
1835:
1828:
1821:
1813:
1805:
1804:
1754:
1723:(2): 325–330.
1703:
1667:
1624:
1617:
1586:
1532:
1503:
1474:
1445:
1416:
1409:
1383:
1376:
1350:
1326:(4): 397–400.
1306:
1257:
1228:
1221:
1192:
1156:
1112:
1093:
1058:
1016:
1005:
961:
954:
947:
926:
890:
883:
856:
807:
788:(2): 134–143.
772:
733:
732:
730:
727:
706:
703:
677:
674:
673:
672:
668:
665:
661:
658:
641:
638:
622:
613:
610:
608:
605:
604:
603:
597:
591:
585:
577:
574:
565:
562:
539:
538:Membrane-bound
536:
534:
531:
510:methylene blue
480:
477:
460:
457:
446:hydrogen bonds
438:oxidoreductase
424:
421:
407:and determine
339:
336:
305:
298:
293:
274:
266:
263:
260:
259:
256:
255:
250:
244:
243:
238:
232:
231:
226:
220:
219:
211:
210:
201:
195:
194:
183:
176:
175:
170:
164:
163:
158:
152:
151:
146:
140:
139:
134:
128:
127:
122:
116:
115:
110:
104:
103:
99:
98:
93:
87:
86:
81:
75:
74:
70:
69:
47:Ribbon diagram
45:
37:
36:
26:
9:
6:
4:
3:
2:
2539:
2528:
2525:
2524:
2522:
2512:
2507:
2502:
2501:
2498:
2484:
2480:
2479:
2474:
2471:
2467:
2466:
2461:
2458:
2454:
2453:
2448:
2445:
2441:
2440:
2435:
2432:
2428:
2427:
2422:
2419:
2415:
2414:
2409:
2406:
2402:
2401:
2396:
2395:
2393:
2389:
2383:
2380:
2378:
2375:
2373:
2370:
2368:
2365:
2363:
2360:
2359:
2357:
2353:
2347:
2344:
2342:
2341:Enzyme family
2339:
2337:
2334:
2332:
2329:
2328:
2326:
2322:
2316:
2313:
2311:
2308:
2306:
2305:Cooperativity
2303:
2301:
2298:
2297:
2295:
2291:
2285:
2282:
2280:
2277:
2275:
2272:
2270:
2267:
2265:
2264:Oxyanion hole
2262:
2260:
2257:
2255:
2252:
2250:
2247:
2246:
2244:
2240:
2236:
2229:
2224:
2222:
2217:
2215:
2210:
2209:
2206:
2194:
2191:
2190:
2188:
2185:
2181:
2175:
2172:
2171:
2169:
2166:
2162:
2158:
2152:
2149:
2148:
2146:
2143:
2139:
2135:
2127:
2124:
2122:
2119:
2118:
2117:
2114:
2110:
2107:
2105:
2102:
2100:
2097:
2095:
2092:
2091:
2090:
2089:NADPH oxidase
2087:
2086:
2084:
2082:
2078:
2074:
2068:
2065:
2063:
2060:
2058:
2054:
2051:
2049:
2046:
2045:
2043:
2041:
2037:
2033:
2027:
2025:
2021:
2016:
2014:
2012:
2007:
2006:
2004:
2002:
1998:
1994:
1990:
1985:
1981:
1977:
1973:
1966:
1961:
1959:
1954:
1952:
1947:
1946:
1943:
1931:
1928:
1926:
1923:
1921:
1918:
1916:
1915:NADPH oxidase
1913:
1911:
1908:
1906:
1903:
1901:
1898:
1896:
1893:
1891:
1888:
1886:
1883:
1881:
1878:
1876:
1873:
1871:
1868:
1866:
1863:
1861:
1858:
1856:
1853:
1852:
1849:
1845:
1844:flavoproteins
1841:
1834:
1829:
1827:
1822:
1820:
1815:
1814:
1811:
1793:
1789:
1785:
1781:
1777:
1773:
1769:
1765:
1758:
1750:
1746:
1741:
1736:
1731:
1726:
1722:
1718:
1714:
1707:
1699:
1695:
1691:
1687:
1683:
1679:
1671:
1656:
1652:
1648:
1644:
1640:
1633:
1631:
1629:
1620:
1614:
1610:
1606:
1602:
1595:
1593:
1591:
1582:
1578:
1573:
1568:
1563:
1558:
1555:(4): e24152.
1554:
1550:
1546:
1539:
1537:
1521:
1517:
1513:
1507:
1492:
1488:
1484:
1478:
1463:
1459:
1455:
1449:
1434:
1430:
1426:
1420:
1412:
1406:
1402:
1398:
1394:
1387:
1379:
1373:
1369:
1365:
1361:
1354:
1339:
1334:
1329:
1325:
1321:
1317:
1310:
1302:
1298:
1293:
1288:
1284:
1280:
1276:
1272:
1268:
1261:
1246:
1242:
1238:
1232:
1224:
1218:
1214:
1210:
1206:
1199:
1197:
1181:
1177:
1173:
1172:"CYB5R3 gene"
1167:
1165:
1163:
1161:
1152:
1148:
1143:
1138:
1134:
1130:
1126:
1122:
1118:
1115:
1111:
1102:
1100:
1098:
1089:
1085:
1081:
1077:
1073:
1069:
1062:
1054:
1050:
1045:
1040:
1036:
1032:
1028:
1024:
1020:
1009:
1001:
997:
992:
987:
982:
977:
973:
969:
965:
960:
953:
946:
937:
935:
933:
931:
922:
918:
914:
910:
906:
902:
894:
886:
880:
876:
872:
868:
860:
852:
848:
843:
838:
834:
830:
826:
822:
818:
811:
803:
799:
795:
791:
787:
783:
776:
768:
764:
760:
756:
752:
748:
741:
739:
734:
726:
722:
720:
716:
711:
702:
700:
696:
692:
688:
687:ascorbic acid
682:
669:
666:
662:
659:
656:
652:
647:
642:
639:
636:
632:
628:
623:
620:
619:
618:
601:
598:
595:
592:
589:
586:
583:
580:
579:
573:
571:
561:
559:
555:
550:
546:
530:
528:
524:
520:
515:
511:
507:
503:
499:
495:
485:
476:
474:
470:
469:methemoglobin
465:
456:
453:
451:
447:
443:
439:
429:
420:
418:
412:
410:
406:
402:
398:
394:
390:
385:
383:
379:
375:
371:
369:
365:
361:
358:, located in
357:
356:cytochrome b5
353:
349:
345:
335:
333:
329:
325:
321:
317:
313:
312:methemoglobin
304:
297:
292:
290:
286:
282:
278:
273:
254:
251:
249:
245:
242:
239:
237:
233:
230:
227:
225:
221:
216:
212:
209:
205:
202:
200:
199:Gene Ontology
196:
193:
190:
187:
184:
181:
177:
174:
171:
169:
165:
162:
159:
157:
153:
150:
147:
145:
141:
138:
137:NiceZyme view
135:
133:
129:
126:
123:
121:
117:
114:
111:
109:
105:
100:
97:
94:
92:
88:
85:
82:
80:
76:
71:
65:
61:
56:
52:
48:
43:
38:
33:
30:
19:
2478:Translocases
2475:
2462:
2449:
2436:
2423:
2413:Transferases
2410:
2397:
2254:Binding site
2116:dual oxidase
2115:
2047:
2023:
2019:
2010:
1899:
1879:
1875:Cryptochrome
1796:. Retrieved
1771:
1767:
1757:
1720:
1716:
1706:
1684:(1): 39–47.
1681:
1677:
1670:
1659:. Retrieved
1642:
1603:. Elsevier.
1600:
1552:
1548:
1524:. Retrieved
1515:
1506:
1495:. Retrieved
1486:
1477:
1466:. Retrieved
1457:
1448:
1437:. Retrieved
1428:
1419:
1392:
1386:
1359:
1353:
1342:. Retrieved
1323:
1319:
1309:
1274:
1270:
1260:
1249:. Retrieved
1240:
1231:
1204:
1184:. Retrieved
1175:
1127:(1): 16006.
1124:
1120:
1113:
1109:
1108:"Cytochrome
1071:
1068:Biochemistry
1067:
1061:
1026:
1022:
1008:
971:
967:
958:
951:
950:-Cytochrome
944:
904:
901:Parasitology
900:
893:
866:
859:
827:(1): 26–37.
824:
820:
810:
785:
781:
775:
750:
746:
723:
712:
708:
683:
679:
660:Type III MHb
615:
570:erythrocytes
567:
541:
525:(DPNH) from
490:
466:
462:
454:
435:
413:
393:cytochrome b
386:
372:
344:flavoprotein
341:
338:Introduction
331:
327:
324:erythrocytes
319:
309:
302:
295:
271:
269:
268:
125:BRENDA entry
57:bound. From
51:erythrocytic
29:
2249:Active site
2165:Nitrogenous
1774:(Suppl_1).
667:Type IV MHb
640:Type II MHb
558:cholesterol
554:fatty acids
374:Cytochromes
360:complex III
283:-dependent
270:Cytochrome-
113:IntEnz view
73:Identifiers
2452:Isomerases
2426:Hydrolases
2293:Regulation
2144:or similar
2026:-specific)
2013:-specific)
1895:Flavodoxin
1798:2024-04-14
1661:2024-04-14
1643:StatPearls
1526:2024-03-24
1497:2024-03-24
1468:2024-03-24
1439:2024-03-24
1393:Hematology
1344:2024-04-14
1277:: 101675.
1251:2024-04-14
1186:2024-03-24
974:(1): 118.
964:Reductase"
729:References
676:Treatments
631:congenital
519:diaphorase
508:(TPNH) to
502:glycolysis
473:hemoglobin
450:ferric ion
442:diaphorase
401:base pairs
316:hemoglobin
314:to normal
277:reductase
182:structures
149:KEGG entry
96:9032-25-1
2331:EC number
1788:0039-2499
671:cyanosis.
612:Mutations
432:Medicine.
423:Structure
382:reductase
102:Databases
2527:EC 1.6.2
2521:Category
2355:Kinetics
2279:Cofactor
2242:Activity
2094:P91-PHOX
1792:Archived
1749:37367083
1740:10298695
1655:Archived
1651:30726002
1581:35592205
1520:Archived
1491:Archived
1462:Archived
1433:Archived
1338:Archived
1301:35651520
1245:Archived
1180:Archived
1151:28721264
1088:11695905
1053:31650629
1000:35008543
921:15180316
851:19997042
802:23113554
705:Research
627:cyanosis
547:with an
533:Isoforms
459:Function
348:isoforms
332:in vitro
253:proteins
241:articles
229:articles
186:RCSB PDB
67:.
2511:Biology
2465:Ligases
2235:Enzymes
2186:: other
2142:Quinone
1840:Protein
1698:8821851
1572:9110037
1292:9149194
1142:5515006
1044:6872605
991:8745658
842:2905818
767:3654589
699:oxalate
664:oxygen.
655:Yakutsk
564:Soluble
328:in vivo
208:QuickGO
173:profile
156:MetaCyc
91:CAS no.
84:1.6.2.2
2497:Portal
2439:Lyases
2184:1.6.99
2081:Oxygen
1786:
1768:Stroke
1747:
1737:
1696:
1649:
1615:
1579:
1569:
1549:Cureus
1407:
1374:
1299:
1289:
1219:
1149:
1139:
1086:
1051:
1041:
998:
988:
919:
881:
849:
839:
800:
765:
693:, and
653:, and
651:Navajo
646:myelin
600:CYB5R4
594:CYB5R3
588:CYB5R2
582:CYB5R1
389:heme b
285:enzyme
236:PubMed
218:Search
204:AmiGO
192:PDBsum
132:ExPASy
120:BRENDA
108:IntEnz
79:EC no.
2391:Types
2167:group
2161:1.6.6
2138:1.6.5
2077:1.6.3
2036:1.6.2
1993:1.6.1
1980:NADPH
576:Genes
514:NADPH
500:from
279:is a
168:PRIAM
2483:list
2476:EC7
2470:list
2463:EC6
2457:list
2450:EC5
2444:list
2437:EC4
2431:list
2424:EC3
2418:list
2411:EC2
2405:list
2398:EC1
2040:Heme
2001:NADP
1986:1.6)
1976:NADH
1784:ISSN
1745:PMID
1694:PMID
1647:PMID
1613:ISBN
1577:PMID
1405:ISBN
1372:ISBN
1297:PMID
1217:ISBN
1147:PMID
1084:PMID
1049:PMID
996:PMID
917:PMID
879:ISBN
847:PMID
798:PMID
763:PMID
352:NADH
281:NADH
248:NCBI
189:PDBe
144:KEGG
64:1UMK
1997:NAD
1978:or
1776:doi
1735:PMC
1725:doi
1686:doi
1605:doi
1567:PMC
1557:doi
1397:doi
1364:doi
1328:doi
1287:PMC
1279:doi
1209:doi
1137:PMC
1129:doi
1076:doi
1039:PMC
1031:doi
986:PMC
976:doi
909:doi
905:128
871:doi
837:PMC
829:doi
790:doi
755:doi
751:101
717:or
471:to
405:DNA
289:FAD
224:PMC
180:PDB
60:PDB
55:FAD
49:of
2523::
2163::
2140::
2079::
2038::
2024:Si
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