Metabolism of Benzoquinone by Yeast Cells and Oxidative Characteristics of Corresponding Hydroquinone: Application to Highly Sensitive Measurement of Yeast Cell Density by Using Benzoquinone and a Chemiluminescent Probe

Tsukatani, Tadayuki; Ide, Seiji; Ukeda, Hiroyuki; Matsumoto, Kiyoshi

doi:10.1271/bbb.68.1525

Cited by 5 publications

(2 citation statements)

References 17 publications

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“…Such a hypothesis was proved by the experimental facts that the substantial generation of hydrogen peroxide was observed in the procedure of TS metabolism in the cytosol and S9 fractions using NADPH as the cofactor, and the addition of UDPGA completely inhibited the hydrogen peroxide generation. The quinone reduction and subsequent autoxidation, which was known as the quinone redox cycle, had been widely observed for many other quinones [33,34].…”

Section: Discussionmentioning

confidence: 96%

Identification of a Novel Intestinal First Pass Metabolic Pathway: NQO1 Mediated Quinone Reduction and Subsequent Glucuronidation

Hao

Wang²,

Cui³

et al. 2007

CDM

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Quinones represent a very important class of compounds found in nature and for the chemically synthesized drugs. The present study was designed to elucidate the intestinal first pass metabolic pathways in vivo and in vitro, of tanshinone IIA (TS), a derivative of phenanthrene-quinone isolated from Salvia miltiorrhiza. Five metabolites, proposed to be TS catechol glucuronides (two position isomers), dehydrotanshinone IIA and its two catechol glucuronides, were identified from the rat intestinal homogenates after oral administration of TS. TS metabolism was further conducted in the subcellular system including cytosol, microsomes, mitochondrial and S9 under both phase I and phase II metabolic conditions. TS underwent negligible metabolism in all of the subcellular systems under phase I metabolic condition using NADPH as the cofactor. However, significant and substantial metabolic elimination of TS was observed in the cytosol and S9 fractions, while not in the microsomes fractions, when both NADPH and UDPGA were added. Two TS catechol glucuronides were identified from such an in vitro metabolic medium. Dicoumarol, a specific inhibitor of the NAD(P)H dependent quinone oxidoreductase (NQO1), significantly inhibited the metabolic elimination of TS in a noncompetitive way, suggesting that NQO1 was responsible for the quinone reduction of TS to form the catechol intermediate. The catechol intermediate failed to be detected directly was proved to be highly unstable and autoxidized back to TS accompanied with hydrogen peroxide generation. Dicoumarol exhibited a significant inhibitory effect on the hydrogen peroxide generation, further supporting that the reduction of TS was catalyzed by NQO1. The absolute bioavailability of TS was significantly enhanced by oral dicoumarol pretreatment. In conclusion, a novel intestinal metabolic pathway for quinones, NQO1 mediated reduction and subsequent glucuronidation, was determined using TS as a model compound. This study should be helpful for the general understanding of quinones absorption and intestinal first pass metabolism.

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Section: Discussionmentioning

confidence: 96%

Identification of a Novel Intestinal First Pass Metabolic Pathway: NQO1 Mediated Quinone Reduction and Subsequent Glucuronidation

Hao

Wang²,

Cui³

et al. 2007

CDM

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“…The mechanism of the autoxidation of PCB derived hydroquinone may be similar to 1,4-hydroquinone because of their similar thermodynamic and kinetic properties. (shown in Eq 3An induction period has been reported in the studies on the autoxidation process of some hydroquinone family members(14,43,64). James et al(61) reported that various methyl-substituted 1,4-hydroquinones autoxidize after an induction period.…”

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confidence: 90%

Glutathione suppresses the autoxidation of 2',5'-dihydroxy-4-chlorobiphenyl

Chen¹

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Polychlorinated biphenyls (PCBs) are well known as classic environmental pollutants. Lower halogenated PCBs are mainly metabolized to mono-and di-hydroxyl compounds, and the latter further oxidized to quinones through a semiquinone intermediate. These quinone or semiquinone metabolites of PCBs can induce cytotoxicity by conjugating with functional protein and DNA as well as leading to oxidative stress in cells. Glutathione (GSH) is involved in lower chlorinated PCBs metabolites induced toxicities. Previous studies have shown that GSH reacts readily with PCB-quinones through Michael addition. The goal of this thesis was to investigate the effect of GSH on the reaction kinetics of PCB-hydroquinone autoxidation. Quinones produced during the autoxidation of hydroquinones serve as catalysts of the oxidation reaction. Therefore, it is hypothesized that GSH will suppress the autoxidation of PCB-hydroquinone and inhibit the formation of PCB-quinone. One of the PCB-hydroquinones, 2',5'-dihydroxy-4-chlorobiphenyl (4-CB-2',5'-OH), was employed as a model compound. Methods were established with 1,4hydroquinone (1,4-H 2 Q). The reaction rate of 4-CB-2',5'-OH autoxidation showed pH dependency from my study. Superoxide dismutase (SOD) accelerated the reaction rate of 4-CB-2',5'-OH autoxidation dramatically at neutral pH. I used SOD in the studies to explore the effect of GSH on the autoxidation of 4-CB-2',5'-OH at near-neutral pH. It was found that GSH suppressed the autoxidation of 4-CB-2',5'-OH by inhibiting the formation of corresponding 4-CB-2',5'-Q and 4-CB-2',5'-SQ •−. A mathematical model simulating the inhibiting effect of GSH on the autoxidation of 4-CB-2',5'-OH was constructed. The mathematical model reproduced my v experimental data well, supporting my proposed mechanism for the autoxidation of the PCB-derived hydroquinones. I also explored the reaction kinetics of 4-CB-2',5'-OH autoxidation in cell culture medium with fetal bovine serum (FBS). FBS showed a parallel inhibiting effect on 4-CB-2',5'-OH autoxidation as GSH. In summary, GSH and other thiols present in FBS can suppress the autoxidation of lower halogenated PCB-hydroquinone and decrease the rate of PCB-quinone formation. This finding suggests an unrecognized role for GSH in the toxicity of lower chlorinated PCBs. vi TABLE OF CONTENTS LIST OF TABLES .

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Current awareness on yeast

2003

Yeast

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In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (9 weeks journals ‐ search completed 5th. Nov. 2003)

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Metabolism of Benzoquinone by Yeast Cells and Oxidative Characteristics of Corresponding Hydroquinone: Application to Highly Sensitive Measurement of Yeast Cell Density by Using Benzoquinone and a Chemiluminescent Probe

Cited by 5 publications

References 17 publications

Identification of a Novel Intestinal First Pass Metabolic Pathway: NQO1 Mediated Quinone Reduction and Subsequent Glucuronidation

Identification of a Novel Intestinal First Pass Metabolic Pathway: NQO1 Mediated Quinone Reduction and Subsequent Glucuronidation

Glutathione suppresses the autoxidation of 2',5'-dihydroxy-4-chlorobiphenyl

Current awareness on yeast

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