Quinone Metabolism Research Articles

Carbonyl reducing 17 beta-hydroxysteroid dehydrogenase from the filamentous fungus Cochliobolus lunatus.

Hydroxysteroid dehydrogenases (HSDs) which catalyse reversible oxidoreduction of ketosteroids and their respective hydroxysteroids have often been found to have additional substrate specificities towards nonsteroidal ketones, aldehydes and quinones (Maser, 1995). In mammals, such pluripotent enzymes were found in peripheral (Boutin, 1986; Hara et al., 1986;Hara et al. 1986a; Sawada et al., 1988; Klein et al., 1992; Maser and Bannenberg, 1994; Deyashiki et al., 1994; Ohara et al., 1994; Maser, 1995; Oppermann et al., 1995) as well as steroidogenic tissues (Tanaka et al., 1992; Nakajin et al., 1994; Jarabak et al., 1996). They were supposed to be involved in the detoxification of xenobiotic carbonyl compounds in addition to their role in the metabolism of endogenous steroids, prostaglandins, and quinones (Maser and Bannenberg, 1994; Oppermann et al., 1995). In microorganisms it has been shown for some bacterial HSDs that they have the versatility to accept steroidal as well as non-steroidal substrates (Oppermann et al., 1993; Maser, 1995). On the other hand, pluripotency of fungal HSD has not been discovered. Recently, 17β-hydroxysteroid dehydrogenase (17β-HSD) from the fungus Cochliobolus lunatus was purified and some of its molecular and kinetic properties were characterized (Lanisnik Rižner et al., 1996). In the present paper we provide further characterization of this enzyme and also some data indicating that it is a fungal enzyme with carbonyl reductase activity.

Metabolism of simple quinones in guinea pig and rat cardiac tissue

1. 1. The metabolism of the benzoquinone 2,5-dimethylbenzoquinone and of the naphthoquinone 2,3-dimethoxy-1,4-naphthoquinone was studied in subcellular fractions isolated from cardiac tissue of guinea pig and rat. 2. 2. In both species the benzoquinone was mainly metabolized through the mitochondrial NADH-ubiquinoneoxidoreductase, whereas the naphthoquinone was metabolized to approximately equal extents by mitochondrial reductase and by soluble DT-diaphorase. 3. 3. Guinea pig heart metabolized 3 times more naphthoquinone than rat heart. 4. 4. As a consequence of quinone metabolism, marked amounts of O 2: were generated; naphthoquinoneinduced O 2+: generation was about 4-fold higher in guinea pig than in rat heart.

Gene Targeting of DT-Diaphorase in Mouse Embryonic Stem Cells: Establishment of Null Mutant and Its Mitomycin C-Resistance

It is generally accepted that DT-diaphorase is primarily involved in the detoxification of quinone compounds and is capable of metabolically activating some cancer chemotherapeutic quinones including mitomycin C. However, these conclusions have mainly been drawn from the experiments using the DT-diaphorase inhibitor, dicoumarol. To understand directly the roles of this enzyme in quinone metabolism, we have established heterozygously and homozygously DT-diaphorase-targeted mutant embryonic stem (ES) cells by homologous recombination. Cytotoxicity experiments using these cells clearly demonstrated that DT-diaphorase acts as an activator of mitomycin C in ES cells. These mutant cell lines seem to be very useful for investigating the functions of DT-diaphorase including the bioactivation and detoxification of quinone species. The generation of a DT-diaphorase-targeted mouse is under investigation.

Definition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure.

Inositol polyphosphate 1-phosphatase, inositol monophosphate phosphatase, and fructose 1,6-bisphosphatase share a sequence motif, Asp-Pro-(Ile or Leu)-Asp-(Gly or Ser)-(Thr or Ser), that has been shown by crystallographic and mutagenesis studies to bind metal ions and participate in catalysis. We compared the six alpha-carbon coordinates of this motif from the crystal structures of these three phosphatases and found that they are superimposable with rms deviations ranging from 0.27 to 0.60 A. Remarkably, when these proteins were aligned by this motif a common core structure emerged, defined by five alpha-helices and 11 beta-strands comprising 155 residues having rms deviations ranging from 1.48 to 2.66 A. We used the superimposed structures to align the sequences within the common core, and a distant relationship was observed suggesting a common ancestor. The common core was used to align the sequences of several other proteins that share significant similarity to inositol monophosphate phosphatase, including proteins encoded by fungal qa-X and qutG, bacterial suhB and cysQ (identical to amtA), and yeast met22 (identical to hal2). Evolutionary comparison of the core sequences indicate that five distinct branches exist within this family. These proteins share metal-dependent/Li(+)-sensitive phosphomonoesterase activity, and each predicted tree branch exhibits unique substrate specificity. Thus, these proteins define an ancient structurally conserved family involved in diverse metabolic pathways including inositol signaling, gluconeogenesis, sulfate assimilation, and possibly quinone metabolism. Furthermore, we suggest that this protein family identifies candidate enzymes to account for both the therapeutic and toxic actions of Li+ as it is used in patients treated for manic depressive disease.

Antioxidant and prooxidant functions of DT-diaphorase in quinone metabolism.

Antioxidant and prooxidant functions of DT-diaphorase in quinone metabolism.

Isolation and characterization of substituted 4-hydroxy-cyclohex-2-enones as metabolites of 3,4-dimethoxybenzyl alcohol and its methyl ether in ligninolytic cultures of Phanerochaete chrysosporium

The metabolism of quinones formed in the enzymatic oxidation of veratryl alcohol (3,4-dimethoxybenzyl alcohol) (Ia) and its methyl ether Ib in ligninolytic cultures of Phanerochaete chrysosporium was studied. A metabolite of 2-hydroxymethyl-5-methoxy-2,5-cyclohexadiene-1,4-dione (IIa, formed from Ia by oxidation) was isolated and identified as cis-4-hydroxy-6-hydroxymethyl-3-methoxy-cyclohex-2-en-one (IVa), formally the reduced hydroquinone IIIa. The formation of IVa was also observed when both veratryl alcohol Ia or 2,5-dihydroxy-4-methoxybenzyl alcohol (IIIa), the hydroquinone of IIa, were used as substrates. Analogously, cis-4-hydroxy-3-methoxy-6-methoxymethyl-cyclohex-2-en-one (IVc) was isolated and identified as a metabolite from either 3,4-dimethoxybenzyl methyl ether (Ib) or from its oxidation product 5-methoxy-2-methoxymethyl-2,5-cyclohexadiene-1,4-dione (IIb) as well as from the corresponding hydroquinone 2,5-dihydroxy-4-methoxybenzyl methyl ether (IIIc). The physiological role of these unprecedented conversions is discussed.

DT diaphorase [NAD(P)H: (quinone acceptor) oxidoreductase] in channel catfish (Ictalurus punctatus): kinetics and distribution

The flavin-containing enzyme, DT diaphorase [NAD(P)H: (quinone acceptor) oxidoreductase. DTD] has been studied extensively in mammalian species as a quinone detoxifying agent. However. DTD in aquatic species has received relatively little attention. DTD activity (dicoumarul-sensitive dichlorophe-nolindophenol reduction) was characterized in four organs of the channel catfish. Ictalurus punctatus. Optimal conditions of substrate and cofactor concentration for hepatic cytosolic activity were determined. Alkaline pH activity data indicated that DTD activity in the organs tested was maximal in the pH range 7–9 and declined at higher values. Detectable DTD activities were observed in liver mitochondrial, micro-somal and cytosolic fractions. A distinct gradient in cytosolic DTD levels among four organs was observed as follows: stomach > gill > liver > posterior kidney. This gradient was demonstrated in tissues of juvenile as well as adult male and female fish, with no qualitative differences in the gradient among the three groups. Inhibition of DTD by the anticoagulant dicoumarol was observed to be competitive with respect to NADH. Kinetic data revealed no apparent gradient in either K m or K i values corresponding to the observed organ-specific activity gradient. The implications of the observed interorgan differences in DTD activity and the role of this enzyme in quinone metabolism are discussed.

Reductase and oxidase activity of rat liver cytochrome P450 with 2,3,5,6-tetramethylbenzoquinone as substrate

The main objective of the present study was to investigate the proposed role of cytochrome P450 in the reductive metabolism of quinones as well as in the formation of reduced oxygen species in liver microsomes from phenobarbital (PB-microsomes) and β-naphthoflavone (βNF-microsomes) pretreated rats. In the present study, 2,3,5,6-tetramethylbenzoquinone (TMQ) was chosen as a model quinone. Anaerobic one-electron reduction of TMQ by PB-microsomes showed relatively strong electron spin resonance (ESR) signals of the oxygen-centered semiquinone free radical (TMSQ), whereas these signals were hardly detectable with βNF-microsomes. Under aerobic conditions TMSQ formation was diminished and concomitant reduction of molecular oxygen occured in PB-microsomes. Interestingly, TMQ-induced superoxide anion radicals, measured by ESR (using the spin trap 5,5′-dimethyl-1-pyrroline- N-oxide), and hydrogen peroxide generation was found to occur with βNF-microsomes as well. Furthermore, SK&F 525-A (a type I ligand inhibitor of cytochrome P450) inhibited TMQ-induced hydrogen peroxide formation in both PB- and βNF-microsomes. However, metyrapone and imidazole (type II ligand inhibitors of cytochrome P450) inhibited molecular oxygen reduction in βNF-microsomes and not in PB-microsomes. The present study indicates that cytochrome P450-mediated one-electron reduction of TMQ to TMSQ and subsequent redox cycling of TMSQ with molecular oxygen constitutes the major source for superoxide anion radical and hydrogen peroxide generation in PB-microsomes (i.e. from the reductase activity of cytochrome P450). However, most of the superoxide anion radical formed upon aerobic incubation of TMQ with βNF-microsomes originates directly from the dioxyanion-ferri-cytochrome P450 complex (i.e from the oxidase activity of cytochrome P450). In conclusion, both the one-electron reduction of TMQ and molecular oxygen were found to be cytochrome P450 dependent. Apparently, both the reductase and oxidase activities of cytochrome P450 may be involved in the reductive cytotoxicity of chemotherapeutic agents containing the quinoid moiety.

DT diaphorase [NAD(P)H: (Quinone acceptor) oxidoreductase] facilitates redox cycling of menadione in channel catfish ( Ictalurus punctatus) cytosol

Characteristics of DT diaphorase (NAD(P)H: (quinone acceptor) oxidoreductase, DTD) activity in Ictalurus punctatus and the effect of DTD activity on menadione (MND)-mediated reduction of acetylated cytochrome c (AcC) were examined. DTD activity in cytosols of four organs followed a distinct gradient in the order stomach > gill > liver > posterior kidney. A similar gradient was observed in organ-specific rates of in vitro AcC reduction in the presence of either NADH or NADPH as reducing equivalent. A greater proportion of the AcC reduction rate was sensitive to inhibition by dicoumarol (DC) in organs with relatively high DTD specific activity (e.g., stomach) than in organs with low DTD activity (e.g., kidney). No such trend was observed in the superoxide dismutase (SOD)-sensitive proportion of AcC reduction rates. DTD was observed to contribute to MND-mediated superoxide production to a greater extent in organs with high DTD activity than in organs with low DTD activity. DC-sensitive (i.e., DTD-mediated) AcC reduction was observed to increase with organ-specific DTD activity, and the majority of the AcC reduction rate was inhibitable by SOD. These findings demonstrate a direct contribution by DTD activity to MND-mediated superoxide production in this in vitro system. The role of I. punctatus DTD as a possible deleterious agent in quinone metabolism and implications regarding the traditional conception of DTD as a detoxifying enzyme are discussed.

Inhibition of estrogen-induced kidney carcinogenesis in Syrian hamsters by modulators of estrogen metabolism

Quinone metabolites of catechol estrogens have been postulated to mediate estradiol-induced carcinogenesis. In this study, this postulate was examined by investigating the effect of modulators of quinone metabolism on estradiol-induced tumor incidence in male Syrian hamsters. 2(3)-t-Butyl-4-hydroxyanisol (BHA) and dicumarol which are known to stimulate or inhibit respectively, the activity of quinone reductase, lowered tumor incidence by 33 and 42% respectively (3/9 and 5/12 tumor-free animals/total respectively), from 100% (13/13) observed with 17 beta-estradiol (E2) treatment only. Ebselen, a substance with glutathione peroxidase-like activity, and sodium 2-mercaptoethanesulfonate (Mesna), a cytoprotective thiol-containing agent, were only marginally effective in decreasing the estradiol-induced kidney tumor incidence (3/11 and 4/19 tumor-free animals/total respectively). The lowering of tumor incidence by BHA and dicumarol correlated well with a 40-45% decrease in renal peroxidatic activity of cytochrome P450 in hamsters treated with these substances plus estradiol for 1 month. In addition, these compounds also inhibited the oxidation of diethylstilbestrol to its corresponding quinone in vitro. An influence on quinone reductase or other detoxifying enzymes in chronically treated male Syrian hamsters could not be detected. These data support a mediation of estradiol-induced carcinogenesis by quinones formed by metabolic oxidation of catechol estrogens.

Relative metabolism of quinones to semiquinone radicals in xanthine oxidase system

Rates of enzymatic single-electron reduction of some myotoxic quinones to semiquinone metabolites in an in vitro xanthine oxidase/hypoxanthine/catalase system varied widely. Naphthoquinones, especially juglone, were found to undergo rapid single-electron reduction. Benzoquinones and benzoquinoneimines, as well as phenanthrene-9,10-quinone, benzo[a]pyrene-3,6-quinone, and diethylstilbestrolquinone, were also actively reduced. The anthraquinones danthron, doxorubicin and emodin were poorly metabolized in this system. N-Acetylcysteine inhibited quinone-stimulated cytochrome C reduction at high concentrations. The results of this study are discussed with respect to cytotoxicity and mutagenicity of selected quinones.

Characterization of free radicals produced during oxidation of etoposide (VP-16) and its catechol and quinone derivatives. An ESR study

Spectroscopic evidence for the radical-mediated metabolism of VP-16, VP-16 catechol, and VP-16 quinone during enzymatic oxidation and autoxidation has been obtained. Autoxidation of the catechol yields the primary semiquinone together with the primary molecular product VP-16 quinone, which subsequently undergoes hydrolytic oxidation to form secondary quinones and semiquinones. Both primary and secondary phenoxyl radicals were detected during peroxidatic oxidation of VP-16. Neither the primary nor the secondary radicals react with DNA at a detectable rate. Evidence for the production of hydroxyl radical during iron-catalyzed oxidation of VP-16 catechol was obtained. These free radical reactions may have implications for the mechanism of antitumor action of VP-16.

Cytoskeletal alterations in human platelets exposed to oxidative stress are mediated by oxidative and Ca 2+-dependent mechanisms

The metabolism of the redox-active quinone, menadione (2-methyl-1,4-naphthoquinone), in human platelets was associated with superoxide anion production, oxidation and depletion of intracellular glutathione, and modification of protein thiols. The cytoskeletal fraction extracted from menadione-treated platelets exhibited a dose-dependent increase in the amount of cytoskeleton-associated protein and a concomitant loss of protein thiols. These alterations were associated with oxidative modifications of actin, including β-mercaptoethanol-sensitive crosslinking of actin to form dimers, trimers, and high-molecular-weight aggregates which also contained other cytoskeletal proteins, i.e., α-actinin and actin-binding protein. In addition, analysis of the cytoskeletal fraction from platelets treated with high concentrations (⩾100 μ m) of menadione by polyacrylamide gel electrophoresis under reducing conditions revealed a net decrease in the relative abundance of the individual cytoskeletal polypeptides. Under the same incubation conditions the platelets exhibited a sustained increase in cytosolic Ca 2+ concentration. The presence of glucose, or the omission of Ca 2+ from the incubation medium, prevented both the increase in cytosolic Ca 2+ and the decrease in the relative amounts of cytoskeletal proteins. The latter effect was also largely prevented in platelets loaded with Quin-2 tetraacetoxymethyl ester to buffer the menadione-induced elevation of cytosolic Ca 2+. Finally, the presence of a protease inhibitor, leupeptin, in the incubation medium prevented the menadione-induced decrease in the amount of actin-binding protein but not the decrease in the other cytoskeletal proteins. Our findings demonstrate that the multiple effects of oxidative stress on the platelet cytoskeleton are mediated by oxidative as well as by Ca 2+-dependent mechanisms.

Effects of Cassia obtusifolia (sicklepod) extracts and anthraquinones on muscle mitochondrial function

Effects of Cassia obtusifolia (sicklepod) extracts and anthraquinones on muscle mitochondrial function. Toxicon 27, 519–529, 1989.—Naturally occurring quinones and quinone-containing extracts of seeds of the toxic plant Cassia obtusifolia (sicklepod) affected muscle mitochondrial function. Aqueous suspensions and organic extracts of C. obtusifolia seeds slightly elevated plasma creatine kinase levels of Sprague-Dawley rats. These extracts were analyzed by fused silica capillary gas chromatography and found to contain nine anthraquinones and three anthrones. Urinary metabolites primarily consisted of β-glucuronide conjugates of the anthraquinones. The three anthrones or conjugate analogues were not present in the urine in detectable amounts. Emodin, doxorubicin and organic extracts of C. obtusifolia inhibited NADH:cytochrome c oxidoreductase activity of bovine heart mito-chondrial particles and NADH:CoQ oxidoreductase activity of porcine heart mitochondrial NADH dehydrogenase, whereas juglone was stimulatory. Relative quinone metabolism correlated with semiquinone formation rate and with redox potential. A protective effect of coenzyme Q against enzyme inhibition by anthraquinones was also observed.

Alterations in hepatocyte cytoskeleton caused by redox cycling and alkylating quinones

Quinones may induce toxicity by a number of mechanisms, including alkylation and oxidative stress following redox cycling. The metabolism of quinones by isolated rat hepatocytes is associated with cytoskeletal alterations, plasma membrane blebbing, and subsequent cytotoxicity. The different mechanisms underlying the effects of alkylating ( p-benzoquinone), redox cycling (2,3-dimethoxy-1,4-naphthoquinone), and mixed redox cycling/alkylating (2-methyl-1,4-naphthoquinone) quinones on hepatocyte cytoskeleton have been investigated in detail in this study. Analysis of the cytoskeletal fraction extracted from quinone-treated cells revealed a concentration-dependent increase in the amount of cytoskeletal protein and a concomitant loss of protein thiols, irrespective of the quinone employed. In the case of redox cycling quinones, these alterations were associated with an oxidation-dependent actin crosslinking (sensitive to the thiol reductant dithiothreitol). In contrast, with alkylating quinones an oxidation-independent cytoskeletal protein crosslinking (insensitive to thiol reductants) was observed. In addition to these changes, a dose-dependent increase in the relative abundance of F-actin was detected as a consequence of the metabolism of oxidizing quinones in hepatocytes. Addition of dithiothreitol solubilized a considerable amount of polypeptides from the cytoskeletal fraction isolated from hepatocytes exposed to redox cycling but not alkylating quinones. Our findings indicate that the hepatocyte cytoskeleton is an important target for the toxic effects of different quinones. However, the mechanisms underlying cytoskeletal damage differ depending on whether the quinone acts primarily by oxidative stress or alkylation.

Synthesis of spin traps specific for hydroxyl radical.

Two nitrones, 3,3-diethyl-5,5-dimethylpyrroline 1-oxide (DEDMPO) and 3,3,5,5-tetramethylpyrroline 1-oxide (M4PO), were synthesized by the zinc/ammonium chloride reduction of appropiately substituted gamma-nitrocarbonyl compounds, followed by addition of methylmagnesium bromide to the resulting intermediate nitrones. The lipophilicities of these nitrones were estimated by determining their partition coefficients in an 1-octanol/water system. They were found to be considerably more lipophilic than 5,5-dimethylpyrroline 1-oxide (DMPO). The spin trapping of hydroxyl and superoxide radicals with these nitrones was investigated, and the hyperfine coupling constants were determined. M4PO was found to spin trap both free radicals, while DEDMPO spin trapped only hydroxyl radical. DEDMPO was used to determine if hydroxyl radical was produced during the metabolism of menadione or nitrazepam by porcine thoracic aorta endothelial cells. Our results indicate, in conjunction with spin-trapping studies utilizing DMPO, that only superoxide is generated during cellular metabolism of quinones and aromatic nitro-containing compounds by endothelial cells.

Singlet oxygen in biological systems

Electronically excited molecular oxygen ( 2Δ g O 2) is of increasing interest in biology and medicine. Several methods have been employed for detection and identification, including chemical trapping and the continuous and non-invasive monitoring of low-level chemiluminescence in the visible and infrared spectral region due to the bi- and monomolecular transition of the excited molecules to the ground state. Performing spectral analysis and measuring the effect of D 2O and/or 1O 2 quenchers, evidence for the involvement of this reactive oxygen species in a variety of non-enzymatic and enzyme-catalyzed reaction pathways of biological and medical importance has been provided. The use of the intact perfused rat liver allowed direct monitoring of the metabolism of hydroperoxides and quinones by measuring the photoemission from the organ surface. Occurrence of 1O 2 in cells, generated under physiological conditions or under conditions of oxidative stress, has implications on biological functions at molecular and cellular level. Besides reaction with lipids, inactivation of several enzymes by means of amino acid modification has been demonstrated; also damage of constituents of DNA has been reported. Recently the effect of 1O 2 on the biological activity of intact DNA was investigated, showing the loss of transforming activity of pBR 322 in E. coli upon 1O 2 exposure. Quantification of 1O 2 has been performed during these measurements; quantification of steady states of 1O 2 in more complex systems remains the topic of present work.

Quinone toxicity in hepatocytes: Studies on mitochondrial Ca 2+ release induced by benzoquinone derivatives

Hepatocyte cytotoxicity caused by substituted benzoquinones was associated with increased cytosolic Ca 2+ concentration. p-Benzoquinone-induced hepatotoxicity was enhanced when the hepatocytes were loaded with Ca 2+ by preincubation with ATP. A similar order of potency of the substituted benzoquinones in releasing Ca 2+ from isolated mitochondria and inducing hepatocyte cytotoxicity was found; in decreasing order, this was 2-Br-, unsubstituted-, 2-CH 3-, 2,6-(CH 3O) 2-, 2,6-(CH 3) 2-, 2,5-(CH 3) 2-, 2,3,5-(CH 3) 3-, and 2,3,5,6-(CH 3) 4-benzoquinones (duroquinone). The cellular products of quinone metabolism, hydroquinones and glutathione conjugates, did not cause mitochondrial Ca 2+ release. Benzoquinone-induced mitochondrial Ca 2+ release was preceded by GSH conjugate formation and NAD(P)H oxidation but followed by mitochondrial swelling. With duroquinone, a slow GSH and NADPH oxidation preceded Ca 2+ release, but GSH oxidation did not occur with Se-deficient mitochondria lacking glutathione peroxidase activity. Cyanide-insensitive respiration was also observed with duroquinone but not with benzoquinone, suggesting that duroquinone undergoes redox cycling. GSH was depleted by both arylation and oxidation with 2,6-(CH 3O) 2-, 2,6-(CH 3) 2-, 2,5(CH 3) 2-, and 2,3,5-(CH 3) 3-benzoquinones. Benzoquinone concentrations that totally depleted GSH did not cause Ca 2+ release until intramitochondrial NAD(P)H was oxidized. Ca 2+ release was also prevented when NAD(P)H generation was stimulated by the presence of isocitrate or 3-hydroxybutyrate. This suggests that mitochondrial Ca 2+ release is associated with NAD(P)H oxidation catalyzed by NADH dehydrogenase with benzoquinone or by the glutathione peroxidase-glutathione reductase system with duroquinone.

Interaction between vitamin K 3 and benzo(a)pyrene metabolism in uninduced microsomes

1. 1. Relationship between quinone recycling, glucuronidation and benzo(a)pyrene (BaP) oxygenation was investigated in uninduced mouse liver microsomes—native and modified by Fe 3+ · FeEDTA and/or superoxide (O 2 −·)-initiated lipid peroxidation. 2. 2. A functional coupling between glucuronidation of reduced quinones and BaP metabolism, not discernible during BaP metabolism by native uninduced microsomes, was demonstrable in the presence of a model quinone, vitamin K 3 (menadione). 3. 3. Menadione inhibited BaP oxygenation in microsomal preparations, by siphoning off electrons from cytochrome P-450, while addition of UDPGA reversed this effect by glucuronidation of menadiol 4. 4. Fe 3+·FeEDTA and/or O 2 −·-initiated lipid peroxidation decreased, to different extent, the microsomal enzymatic activities involved in quinone metabolism. The most sensitive was quinone reductase activity, which was reduced by 77%. Under peroxidative conditions menadione was a less effective inhibitor of BaP metabolism. 5. 5. The important role of the balance between quinone reductase and UDP-glucuronyltransferase activities in the coupling with BaP oxygenation is discussed. A mechanism by which vitamin K 3 could exert a regulatory effect on BaP metabolism is proposed.

Quinones in Biology: Functions in electron transfer and oxygen activation

Abstract The widespread occurrence and function of quinones in diverse biological systems with particular reference to their role in oxygen activation has been reviewed and discussed. The importance of quinones in such basic metabolic processes as respiration and photosynthesis has been well established. Less clear are the conditions which lead to loss of the normal metabolic functions of quinones, often resulting in the generation of active oxygen species. Exogenous quinones have been used extensively as tools to investigate physiological processes. In addition, they are increasingly applied to influence such reactions artificially. In particular, the loss of normal quinone function invariably has toxicological consequences, in which the activation of oxyqen hy quinone redox reactions plays a central role. The present review discusses hiological and toxicological aspects of quinone metabolism. Physical and chemical data are considered in order to attempt to explain the physiological effects.