Hydrogen peroxide-mediated inactivation of microsomal cytochrome P450 during monooxygenase reactions

Karuzina, I I; Archakov, Alexander I.

doi:10.1016/0891-5849(94)90095-7

Cited by 58 publications

(39 citation statements)

References 46 publications

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“…Several mutagenesis approaches showed the possibility to transform conventional P450s into peroxygenases [59,61]. Therefore, peroxygenases have high potential; however, since elevated H 2 O 2 -concentrations are harmful for both, the enzyme and its heme-cofactor [58][59][60], stable variants [59,61] and variants rescuing the heme-cofactor are highly desired. Furthermore, alternative in situ H 2 O 2 -production methods [69,133] or feeding of low amounts of H 2 O 2 may be exploited.…”

Section: Discussionmentioning

confidence: 99%

“…A significant advantage of P450 peroxygenases using H 2 O 2 is the avoidance of NAD(P)H and the possible need for additional enzymes [57]. However, P450 peroxygenases are also prone to inactivation due to the required high concentrations of hydrogen peroxide [58][59][60]. Mutagenesis approaches including directed evolution [61] and site-directed mutagenesis [59] showed successful stabilization and increased activity of peroxygenases.…”

Section: Mechanistic Considerationsmentioning

confidence: 99%

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Regioselective Biocatalytic Hydroxylation of Fatty Acids by Cytochrome P450s

2017

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Section: Discussionmentioning

confidence: 99%

Section: Mechanistic Considerationsmentioning

confidence: 99%

Regioselective Biocatalytic Hydroxylation of Fatty Acids by Cytochrome P450s

2017

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“…The H 2 O 2 is a microsomal ROS product that occurs in reactions involving cytochrome P450 (31). An activity of the cytochrome p450 enzymes may be affected by oxidative stress in the brain and other organs because H 2 O 2 can inhibit cytochrome p450 enzymes (32,33). In the present study, changes in the α-tocopherol acetate level of the H 2 O 2 group may be a result of this interaction.…”

Section: Discussionmentioning

confidence: 61%

Effect of Geraniol on Brain Cholesterol, Vitamin A and E Levels in The Hydrogen Peroxide-Treated Rats

Şahin

2018

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ÖzetAmaç: Bir monoterpen olan geraniol, bazı bitkilerde yer alan doğal bir antioksidandır. Hidrojen peroksit (H 2 O 2 ) ise reaktif oksijen türlerinin (ROS) bir üyesidir. Bu çalışmada, H 2 O 2 uygulanan sıçanlarda geraniolün beyin kolesterolü ve yağda çözünen A (retinol) ve E (alfa (α)-tokoferol ve α-tokoferol asetat) vitaminlerine etkisinin belirlenmesi amaçlanmıştır. Gereçler ve Yöntem: Çalışmada yetişkin erkek Wistar sıçanlar rastgele dört gruba ayrılarak (n=7), geraniol (50mg/kg) ve H 2 O 2 (16mg/kg), intraperitoneal olarak, 30 gün süresince gün aşırı uygulandı. Beyin numuneleri homojenize edildikten sonra kolesterol, α-tokoferol, α-tokoferol asetat ve retinol düzeyleri yağ ekstraktlarından HPLC ile analiz edildi. Bulgular: Beyin kolesterol düzeyinin H 2 O 2 grubunda kontrol grubuna kıyasla daha fazla olduğu belirlendi. H 2 O 2 ve geraniol+ H 2 O 2 gruplarında, beyin α-tokoferol asetat düzeylerinin kontrole kıyasla daha yüksek olduğu bulundu. Beyin retinol seviyesi bakımından grupların hiçbirisinde istatistiksel olarak anlamlı bir değişiklik mevcut değildi. Sonuç: Elde ettiğimiz veriler, beyinde kolesterol ve α-tokoferol asetat düzeylerinin H 2 O 2 ile oluşturulan oksidatif stresten etkilendiğini göstermektedir. Geraniolün erkek sıçanlarda H 2 O 2 'nin etkilerini azaltma potansiyeli olduğu söylenebilir.Anahtar kelimeler: Geraniol, hidrojen peroksit, beyin, kolesterol, α-tokoferol Aim: Geraniol, a monoterpene, is a plant-derived natural antioxidant. Hydrogen peroxide (H 2 O 2 ) is a member of reactive oxygen species (ROS). The objective of this study is to de-termine the effect of geraniol on brain cholesterol and lipophilic vitamins such as vitamin A (retinol) and vitamin E (alpha (α)-tocopherol and α-tocopherol acetate) in H 2 O 2 -administrated male rats. Materials and Methods: Adult male Wistar rats were randomly divided into four groups (n=7). Geraniol (50 mg/kg) and H 2 O 2 (16 mg/kg) were administered by an intraperitoneal injection for 30 days with a 1-day interval. Brain samples were homogenized and cholesterol, α-tocopherol, α-tocopherol acetate, and retinol levels analyzed from lipid extracts by HPLC. Results: Brain cholesterol level was found to be significantly higher in the H 2 O 2 group than the control group. Brain α-tocopherol acetate levels were found to be significantly higher in the H 2 O 2 and the geraniol+H 2 O 2 groups than the control group. There was no difference in retinol levels between any groups. Conclusion: In conclusion, our results indicate that brain cholesterol and α-tocopherol acetate levels are affected by H 2 O 2 -induced oxidative stress. Moreover, we suggest that geraniol has the potential to reduce the effect of H 2 O 2 in male rats. Keywords

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“…Previously, inactivation of CYP2B was proposed to result from the production of H202 (Guengerich and Strickland, 1977;Karuzina and Archakov, 1994), but that inactivation, and hence the mechanism, differs from the inactivation of scup CYP1A. First, CYP2B inactivation occurred with excess NADPH alone and decreased when substrate was added (Guengerich and Strickland, 1977;Loosemore et al, 1980;Karuzina and Archakov, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it was speculated that inactivation may be due to uncoupling of CYP1A and formation of ROS (White et al, 1997a). A number of enzymes (CYP2B, Cu,Zn-superoxide dismutase (SOD), Fe-SOD, lactoperoxidase, myeloperoxidase, xanthine oxidase) that use or produce H202 and that contain· a metal ion undergo oxidative auto-inactivation (Loosemore et al, 1980;Matheson and Travis, 1985;Beyer and Fridovich, 1987;Jenzer et al, 1987;Karuzina and Archakov, 1994).…”

Section: Introductionmentioning

confidence: 99%

Involvement of Cytochrome P450 1A in the toxicity of aryl hydrocarbon receptor agonists : alteration arachidonic acid metabolism and production of reactive oxygen species

Schlezinger¹

1998

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Hydrogen peroxide-mediated inactivation of microsomal cytochrome P450 during monooxygenase reactions

Cited by 58 publications

References 46 publications

Regioselective Biocatalytic Hydroxylation of Fatty Acids by Cytochrome P450s

Regioselective Biocatalytic Hydroxylation of Fatty Acids by Cytochrome P450s

Effect of Geraniol on Brain Cholesterol, Vitamin A and E Levels in The Hydrogen Peroxide-Treated Rats

Involvement of Cytochrome P450 1A in the toxicity of aryl hydrocarbon receptor agonists : alteration arachidonic acid metabolism and production of reactive oxygen species

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