Heme-(hydro)peroxide catalysed O- and N-dealkylation : a study with microperoxidase

M.G. Boersma; J.L. Primus; J. Koerts; C. Veeger; I.M.C.M. Rietjens

doi:10.1046/j.1432-1327.2000.01764.x

Heme-(hydro)peroxide catalysed O- and N-dealkylation : a study with microperoxidase

M.G. Boersma, J.L. Primus, J. Koerts, C. Veeger, I.M.C.M. Rietjens

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Abstract

The mechanism of microperoxidase-8 (MP-8) mediated O- and N-dealkylation was investigated. In the absence of ascorbate (peroxidase mode), many unidentified polymeric products are formed and the extent of substrate degradation correlates (r = 0.94) with the calculated substrate ionization potential, reflecting the formation of radical intermediates. In the presence of ascorbate (P450 mode) formation of polymeric products is largely prevented but, surprisingly, dealkylation is not affected. In addition, aromatic hydroxylation and oxidative dehalogenation is observed. The results exclude a radical mechanism and indicate the involvement of a (hydro)peroxo-iron heme intermediate in P450-type of heteroatom dealkylation.

Original language	English
Pages (from-to)	6673-6678
Journal	European Journal of Biochemistry
Volume	267
DOIs	https://doi.org/10.1046/j.1432-1327.2000.01764.x
Publication status	Published - 2000

Keywords

Cytochrome P450
N-dealkylation
O-dealkylation
Peroxidase

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title = "Heme-(hydro)peroxide catalysed O- and N-dealkylation : a study with microperoxidase",

abstract = "The mechanism of microperoxidase-8 (MP-8) mediated O- and N-dealkylation was investigated. In the absence of ascorbate (peroxidase mode), many unidentified polymeric products are formed and the extent of substrate degradation correlates (r = 0.94) with the calculated substrate ionization potential, reflecting the formation of radical intermediates. In the presence of ascorbate (P450 mode) formation of polymeric products is largely prevented but, surprisingly, dealkylation is not affected. In addition, aromatic hydroxylation and oxidative dehalogenation is observed. The results exclude a radical mechanism and indicate the involvement of a (hydro)peroxo-iron heme intermediate in P450-type of heteroatom dealkylation.",

keywords = "Cytochrome P450, N-dealkylation, O-dealkylation, Peroxidase",

author = "M.G. Boersma and J.L. Primus and J. Koerts and C. Veeger and I.M.C.M. Rietjens",

year = "2000",

doi = "10.1046/j.1432-1327.2000.01764.x",

language = "English",

volume = "267",

pages = "6673--6678",

journal = "European Journal of Biochemistry",

issn = "0014-2956",

publisher = "Wiley",

}

TY - JOUR

T1 - Heme-(hydro)peroxide catalysed O- and N-dealkylation : a study with microperoxidase

AU - Boersma, M.G.

AU - Primus, J.L.

AU - Koerts, J.

AU - Veeger, C.

AU - Rietjens, I.M.C.M.

PY - 2000

Y1 - 2000

N2 - The mechanism of microperoxidase-8 (MP-8) mediated O- and N-dealkylation was investigated. In the absence of ascorbate (peroxidase mode), many unidentified polymeric products are formed and the extent of substrate degradation correlates (r = 0.94) with the calculated substrate ionization potential, reflecting the formation of radical intermediates. In the presence of ascorbate (P450 mode) formation of polymeric products is largely prevented but, surprisingly, dealkylation is not affected. In addition, aromatic hydroxylation and oxidative dehalogenation is observed. The results exclude a radical mechanism and indicate the involvement of a (hydro)peroxo-iron heme intermediate in P450-type of heteroatom dealkylation.

AB - The mechanism of microperoxidase-8 (MP-8) mediated O- and N-dealkylation was investigated. In the absence of ascorbate (peroxidase mode), many unidentified polymeric products are formed and the extent of substrate degradation correlates (r = 0.94) with the calculated substrate ionization potential, reflecting the formation of radical intermediates. In the presence of ascorbate (P450 mode) formation of polymeric products is largely prevented but, surprisingly, dealkylation is not affected. In addition, aromatic hydroxylation and oxidative dehalogenation is observed. The results exclude a radical mechanism and indicate the involvement of a (hydro)peroxo-iron heme intermediate in P450-type of heteroatom dealkylation.

KW - Cytochrome P450

KW - N-dealkylation

KW - O-dealkylation

KW - Peroxidase

U2 - 10.1046/j.1432-1327.2000.01764.x

DO - 10.1046/j.1432-1327.2000.01764.x

M3 - Article

SN - 0014-2956

VL - 267

SP - 6673

EP - 6678

JO - European Journal of Biochemistry

JF - European Journal of Biochemistry

ER -

Heme-(hydro)peroxide catalysed O- and N-dealkylation : a study with microperoxidase

Abstract

Keywords

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