Reduced nicotinamide adenine dinucleotide phosphate dependent biliverdin reductase. Partial purification and characterization

Tenhunen, Raimo; Ross, Michael; Marver, Harvey S.; Schmid, Rudi

doi:10.1021/bi00804a016

Cited by 295 publications

(197 citation statements)

References 10 publications

(7 reference statements)

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“…Heme oxygenase (HO 1 , EC 1.14.99.3) is a microsomal enzyme that catalyzes the O 2 -dependent degradation of heme to biliverdin IXa, carbon monoxide (CO) and free iron at the expense of molecular oxygen and electrons provided by NADPH-cytochrome P450 reductase (CPR, EC 1.6.2.4) [1][2][3]. The degradation of heme to biliverdin by HO proceeds through a multi-step mechanism as shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

Electrochemical reduction of ferrous α-verdoheme in complex with heme oxygenase-1

Satō

Higashimoto

Sakamoto

et al. 2007

Journal of Inorganic Biochemistry

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The heme oxygenase (HO) reaction consists of three successive oxygenation reactions, i.e. heme to α-hydroxyheme, α-hydroxyheme to verdoheme, and verdoheme to biliverdin-iron chelate. Of these, the least understood step is the conversion of verdoheme to biliverdin-iron chelate. For the cleavage of the oxaporphyrin ring of ferrous verdoheme, involvement of a verdoheme π-neutral radical has been proposed. To probe this hypothetical mechanism in the HO reaction, we performed electrochemical reduction of ferrous verdoheme complexed with rat HO-1 under anaerobic conditions. On the basis of the electrochemical spectral changes, the midpoint potential for the oneelectron reduction of the oxaporphyrin ring of ferrous verdoheme was found to be −0.47 ± 0.01 V vs the normal hydrogen electrode (NHE). Because this potential is far lower than those of both flavins of NADPH-cytochrome P450 reductase, and of NADPH, it is concluded that the one-electron reduction of the oxaporphyrin ring of ferrous verdoheme is unlikely to occur and that the formation of the π-neutral radical cannot be the initial step in the degradation of verdoheme by HO. Rather, it appears more reasonable to consider an alternative mechanism in which binding of O 2 to the ferrous iron of verdoheme is the first step in the degradation of verdoheme.

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Section: Introductionmentioning

confidence: 99%

Electrochemical reduction of ferrous α-verdoheme in complex with heme oxygenase-1

Satō

Higashimoto

Sakamoto

et al. 2007

Journal of Inorganic Biochemistry

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“…Heme oxygenase, HO 1 , is a non-metal enzyme that uses protohemin, PH, as both cofactor and substrate to generate biliverdin, iron and CO. 1-6 HOs are widely distributed. In mammals they maintain iron homeostasis, 7 produce the precursor to the powerful antioxidant, 4, 8 biliverdin, and generate CO as a potential neural messenger.…”

Section: Introductionmentioning

confidence: 99%

“…However, the sign (and magnitude) of anisotropy of χ can be directly determined by solution 1 H NMR using experimental dipolar shifts, δ dip , induced in the protein matrix by the anisotropic χ tensor. This shift is given by: 47-49 (1) where x', y', z' (R, θ', Ω') are proton positions in an arbitrary, iron-centered coordinate system, Δχ ax and Δχ rh are the axial (χ zz -1/2(χ xx + χ yy )) and rhombic anisotropies (χ xx -χ yy ), and Γ(α, β, γ) is the Euler rotation that converts the reference coordinates, x', y', z', into the magnetic coordinate system, x, y, z, where χ is diagonal. The anisotropies and orientation of χ can be determined experimentally if sufficient experimental dipolar shifts can be assigned and valid crystal coordinates are available to generate x', y', z'.…”

Section: Introductionmentioning

confidence: 99%

¹H NMR Study of the Magnetic Properties and Electronic Structure of the Hydroxide Complex of Substrate-bound Heme Oxygenase from Neisseria Meningitidis: Influence of the Axial Water Deprotonation on the Distal H-bond Network

Liu

Zhang

et al. 2006

J. Am. Chem. Soc.

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The substrate and active site residues of the low-spin hydroxide complex of the protohemin complex Neisseria meningitidis heme oxygenase, HO, NmHO, have been assigned by saturation transfer between the hydroxide and previously characterized aquo complex. The available dipolar shifts allowed the quantitation of both the orientation and anisotropy of the paramagnetic susceptibility tensor. The resulting positive sign, and reduced magnitude of the axial anisotropy relative to the cyanide complex, dictate that the orbital ground state is the conventional '

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“…These synthetic heme analogs competitively inhibit heme oxygenase (HO), the enzyme that degrades heme to biliverdin, carbon monoxide (CO), and free iron (Fe 2+ ) (7). Biliverdin is subsequently reduced to bilirubin by biliverdin reductase, and the iron-storage protein, ferritin, sequesters Fe 2+ (8,9). Although many Mps have been shown to effectively inhibit bilirubin production, their clinical use has been viewed critically.…”

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confidence: 99%

Effect of light exposure on metalloporphyrin-treated newborn mice

et al. 2012

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Background: Neonatal hyperbilirubinemia arises from increased bilirubin production and decreased bilirubin elimination. Although phototherapy safely and effectively reduces bilirubin levels, recent evidence shows that it has adverse effects. Therefore, alternative treatments are warranted. Metalloporphyrins, competitive inhibitors of heme oxygenase (hO), the rate-limiting enzyme in bilirubin production, effectively reduce bilirubin formation; however, many are photoreactive. here, we investigated possible photosensitizing effects of chromium mesoporphyrin (crMP) and zinc deuteroporphyrin bis-glycol (ZnBG). Methods and results: Administration of crMP or ZnBG to 3-d-old mouse pups (3.75-30.0 µmol/kg intraperitoneally) and exposure to cool white (F20T12cW) and blue (TL20W/52) fluorescent lights (+L) for 3 h, resulted in a dose-dependent mortality (50% lethal dose (LD50) = 21.5 and 19.5 µmol/kg, respectively). In contrast to ZnBG, there was no significant difference in survival between the crMP+L and crMP groups. Following 30 µmol/kg ZnBG+L, we found significant weight loss, decreased liver antioxidant capacities, and increased aspartate aminotransaminase levels. At 6-d post-light exposure, ZnBG+L-treated pups showed gross and histologic skin changes at doses >7.5 µmol/kg. No lethality was observed following treatment with 30 µmol ZnBG/kg plus exposure to blue light-emitting diodes. Phototoxicity of ZnBG was dependent on light source, emission spectrum, and irradiance. conclusion: Low doses of ZnBG (<3.75 µmol/kg) retained maximal hO inhibitory potency without photosensitizing effects, and therefore are potentially useful in treating neonatal hyperbilirubinemia.

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Reduced nicotinamide adenine dinucleotide phosphate dependent biliverdin reductase. Partial purification and characterization

Cited by 295 publications

References 10 publications

Electrochemical reduction of ferrous α-verdoheme in complex with heme oxygenase-1

Electrochemical reduction of ferrous α-verdoheme in complex with heme oxygenase-1

¹H NMR Study of the Magnetic Properties and Electronic Structure of the Hydroxide Complex of Substrate-bound Heme Oxygenase from Neisseria Meningitidis: Influence of the Axial Water Deprotonation on the Distal H-bond Network

Effect of light exposure on metalloporphyrin-treated newborn mice

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Reduced nicotinamide adenine dinucleotide phosphate dependent biliverdin reductase. Partial purification and characterization

Cited by 295 publications

References 10 publications

Electrochemical reduction of ferrous α-verdoheme in complex with heme oxygenase-1

Electrochemical reduction of ferrous α-verdoheme in complex with heme oxygenase-1

1H NMR Study of the Magnetic Properties and Electronic Structure of the Hydroxide Complex of Substrate-bound Heme Oxygenase from Neisseria Meningitidis: Influence of the Axial Water Deprotonation on the Distal H-bond Network

Effect of light exposure on metalloporphyrin-treated newborn mice

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¹H NMR Study of the Magnetic Properties and Electronic Structure of the Hydroxide Complex of Substrate-bound Heme Oxygenase from Neisseria Meningitidis: Influence of the Axial Water Deprotonation on the Distal H-bond Network