Haemoglobin-catalysed retinoic acid 5,6-epoxidation

Iwahashi, Hideo; Ikeda, Akihiko; Kido, Ryō

doi:10.1042/bj2320459

Cited by 8 publications

(8 citation statements)

References 22 publications

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“…While this process is mostly catalyzed by substratespecific enzymes of the cytochrome P450 isoenzyme family, it is interesting to point that also oxyhemoglobin has demonstrated to be able to perform epoxidation on several substrates, such as styrene (Belvedere & Samaja, 1994) and polyunsaturated acids (Iwahashi, Ikeda, & Kido, 1985). The reactivity of circulating scavenging proteins such as hemoglobin and serum albumin with epoxide metabolites has been intensively studied for the measurement of the adducts of several toxicologically relevant olefins, among which ethylene, propene, butadiene and styrene.…”

Section: Reaction With Epoxidesmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

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Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors.

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Section: Reaction With Epoxidesmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

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“…1). The dehydrogenation herein described is a unique reaction since all known epoxidations incorporate molecular oxygen into unsaturated compounds (2,4,5,8,16,21,22). We are now searching for the enzyme(s) that converts Hyos-OH to scopolamine by a cis-dehydrogenation reaction.…”

Section: Methodsmentioning

confidence: 99%

Epoxidation in Vivo of Hyoscyamine to Scopolamine Does Not Involve a Dehydration Step

Hashimoto

Kohno²,

Yamada³

1987

Plant Physiol.

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Hyoscyamine is epoxidized to scopolamine via 6,6-hydroxyhyoscyamine in several solanaceous plants. 6,7-Dehydrohyoscyamine has been proposed to be an intermediate in the conversion of 6#-hydroxyhyoscyamine to scopolamine on the basis of the observation that this unsaturated alkaloid is converted to scopolamine when fed to a Datura scion. To determine whether a dehydration step is involved in scopolamine biosynthesis, 16-'8016j0-hydroxyhyoscyamine was prepared from I-hyoscyamine and '02 using hyoscyamine 6f6-hydroxylase obtained from root cultures of Hyoscyamus niger L. When 16-'8016,-hydroxyhyoscyamine was fed to shoot cultures of Duboisia myoporoides R. BR., the labeled alkaloid was converted to scopolamine which retained "O in the epoxide oxygen. It is concluded that 6,6-hydroxyhyoscyamine is converted in vivo to scopolamine without a dehydration step.Scopolamine, the epoxide of hyoscyamine, is one of the major alkaloids which accumulate in the family Solanaceae (7). The formation of the epoxide bridge in scopolamine begins with the hydroxylation of L-hyoscyamine to Hyos-OH' by a 2-oxoglutarate-dependent dioxygenase, hyoscyamine 6#-hydroxylase (12 De-hyos (scheme 1 in Fig. 1); '"0 should be retained if dehydration is not involved (scheme 2 in Fig. 1). MATERIALS AND METHODSChemicals. '"02 (>99 atom %) was purchased from CEA, France. L-Hyoscyamine hydrobromide and scopolamine hydrobromide were obtained from Nakarai Chemicals, Kyoto. Hyos-OH hydrobromide was prepared using hyoscyamine 6#-hydroxylase from root cultures of Hyoscyamus niger L. (12). De-hyos was synthesized by the method of Sharpless et al. (23). Other chemicals were obtained as described previously (12).Root and Shoot Cultures. Culture conditions for root cultures ofH. niger L. have been reported elesewhere (12). Shoot cultures ofDuboisia myoporoides R. BR. were initiated according to Endo et al. (6) and were subcultured on a Gyrotory shaker (model G 10-21, New Brunswick Scientific, Edison, NJ) at 100 rpm and 25°C under light (2,700-4,500 lux) in 100-ml flasks containing 25 ml of liquid B5 medium (10) supplemented with 3% (w/v) sucrose and 10 Mm 6-BA. In the feeding experiments, alkaloid solutions were neutralized with HCI when necessary and were sterilized by passing through 0.22 Am membrane filters. These were added to 10 ml ofthe above culture medium in 50-ml flasks to a final concentration of0.2 mm. The shoot cultures containing young leaves were inoculated in each flask and cultured under the above conditions.Partial Purification of Hyoscyamine 6,8-Hydroxylase. Hyoscyamine 6t3-hydroxylase was partially purified from root cultures ofH. niger. The hydroxylase in the crude extract was precipitated between 60 and 80% saturation of (NH4)2SO4 and subsequently chromatographed on a DEAE-Toyopearl 650M column. The detailed purification procedure has been reported (13). The partially purified enzyme preparation (about 23-fold in specific activity) was concentrated using Amicon

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“…All reactions were carried out at 37°C for 5 min under aerobic conditions and stopped by the addition of 1.6 ml of methanol containing 50 mM-2-mercaptoethanol. The peak height of the product was compared with those of three different concentrations of 5,6-epoxyretinoic acid standards in the range 5-15 pmol to determine the concentration of 5,6-epoxyretinoic acid formed [5,6]. The concentration of I To whom correspondence should be addressed.…”

Section: Assay Conditionsmentioning

confidence: 99%

“…Indeed, some radical species have been presumed to exist in many biological systems, e.g. lipid peroxidation catalysed by haemoproteins [2], conversion of linoleic acid hydroperoxide into hydroxy, oxo, epoxyhydroxy and trihydroxy fatty acid [3], and epoxidation of7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene [4] and retinoic acid [5,6]. The study of reaction mechanisms containing radical species is important and necessary, since many biological reactions seem to proceed via radical intermediates.…”

Section: Introductionmentioning

confidence: 99%

Inhibition by chlorogenic acid of haematin-catalysed retinoic acid 5,6-epoxidation

Iwahashi¹,

Negoro²,

Ikeda³

et al. 1986

Biochemical Journal

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Chlorogenic acid (3-O-caffeoylquinic acid) inhibited haematin- and haemoglobin-catalysed retinoic acid 5,6-epoxidation. Some other phenol compounds (caffeic acid and 4-hydroxy-3-methoxybenzoic acid) also showed inhibitory effects on the haematin- and haemoglobin-catalysed epoxidation, but salicylic acid did not. Of the above compounds, caffeic acid and chlorogenic acid were potent inhibitors compared with the other two, suggesting that the o-hydroquinone moiety of chlorogenic acid and caffeic acid is essential to the inhibition of the epoxidation. Although caffeic acid inhibited retinoic acid 5,6-epoxidation requiring the consumption of O2, formation of retinoic acid radicals was not inhibited on the addition of caffeic acid to the incubation mixture. The above results suggest that caffeic acid does not inhibit the formation of retinoic acid radicals but does inhibit the step of conversion of retinoic acid radical into the 5,6-epoxide.

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Haemoglobin-catalysed retinoic acid 5,6-epoxidation

Cited by 8 publications

References 22 publications

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Epoxidation in Vivo of Hyoscyamine to Scopolamine Does Not Involve a Dehydration Step

Inhibition by chlorogenic acid of haematin-catalysed retinoic acid 5,6-epoxidation

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