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A I Cederbaum

Publications and source records attributed to A I Cederbaum.

At least 163 records · Page 9Linked to original sources
PubMed1984

Stereochemical studies on the cytochrome P-450 and hydroxyl radical dependent pathways of 2-butanol oxidation by microsomes from chow-fed, phenobarbital-treated, and ethanol-treated rats.

Microsomes have the potential to oxidize alcohols by two pathways, one dependent on hydroxyl radicals (.OH) and the other dependent on cytochrome P-450 in which .OH does not seem to be involved. The possibility that these two pathways may display differences in stereospecificity was evaluated by comparing the oxidation of (+)-2-butanol, (-)-2-butanol, and racemic 2-butanol. Microsomes oxidized 2-butanol to 2-butanone by a reaction which was partially sensitive to carbon monoxide and to competitive .OH scavengers. Desferrioxamine, which completely blocks the production of .OH by microsomes, inhibited the oxidation of ethanol by about 60%, while the oxidation of 2-butanol and 1-butanol was decreased by only 30%. Vmax values for the oxidation of ethanol, 1-butanol, and 2-butanol were 17.7, 6.2, and 23.8 nmol min-1 (mg of protein)-1, respectively, in the absence of desferrioxamine and 5.9, 4.7, and 13.6 nmol min-1 (mg of protein)-1, respectively, in the presence of desferrioxamine. 2-Butanol appears to be a particularly good alcohol substrate for the cytochrome P-450 dependent pathway of alcohol oxidation. Chronic ethanol consumption, which induces the microsomal alcohol oxidizing system, resulted in a 3-fold increase in the rate of 2-butanol oxidation. Most of this increment reflected an increased rate of metabolism by the cytochrome P-450 pathway. A type 2 binding spectrum was observed for the interaction of 2-butanol with microsomes from ethanol-fed rats, but not with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Increased microsomal oxidation of alcohols after pyrazole treatment and its similarities to the induction by ethanol consumption.

Microsomes isolated from rats treated for 3 days with 200 mg/kg body wt. per day of pyrazole, a potent inhibitor of alcohol dehydrogenase, catalyzed the oxidation of ethanol and 2-butanol at rates 2-3-fold higher than saline controls. This increase was blocked by carbon monoxide, and was not associated with an increase in the oxidation of aminopyrine or in the content of cytochrome P-450, suggesting the possibility of an induction of an alcohol-preferring cytochrome P-450 by pyrazole. Microsomes from the pyrazole-treated rats displayed a stereochemical preference for the oxidation of the (+)-2-butanol isomer over the (-)-2-butanol isomer, which was blocked by carbon monoxide, and also displayed a type-2 binding spectrum with dimethylsulfoxide or 2-butanol. No such spectrum was found with the saline controls. These properties are similar to those which are observed with microsomes from chronic ethanol-fed rats. These similarities suggest the possibility that pyrazole treatment may induce a cytochrome P-450 isozyme with properties similar to the ethanol-inducible cytochrome P-450.

1-Butanol↗
PubMed1984

Inhibition of the oxidation of acetaldehyde and formaldehyde by hepatocytes and mitochondria by crotonaldehyde.

Crotonaldehyde was oxidized by disrupted rat liver mitochondrial fractions or by intact mitochondria at rates that were only 10 to 15% that of acetaldehyde. Although a poor substrate for oxidation, crotonaldehyde is an effective inhibitor of the oxidation of acetaldehyde by mitochondrial aldehyde dehydrogenase, by intact mitochondria, and by isolated hepatocytes. Inhibition by crotonaldehyde was competitive with respect to acetaldehyde, and the Ki for crotonaldehyde was about 5 to 20 microM. Crotonaldehyde had no effect on the oxidation of glutamate or succinate. Very low levels of acetaldehyde were detected during the metabolism of ethanol. Crotonaldehyde increased the accumulation of acetaldehyde more than 10-fold, indicating that crotonaldehyde, besides inhibiting the oxidation of added acetaldehyde, also inhibited the oxidation of acetaldehyde generated by the metabolism of ethanol. Formaldehyde was a substrate for the low-Km mitochondrial aldehyde dehydrogenase, as well as for a cytosolic, glutathione-dependent formaldehyde dehydrogenase. Crotonaldehyde was a potent inhibitor of mitochondrial oxidation of formaldehyde, but had no effect on the activity of formaldehyde dehydrogenase. In hepatocytes, crotonaldehyde produced about 30 to 40% inhibition of formaldehyde oxidation, which was similar to the inhibition produced by cyanamide. This suggested that part of the formaldehyde oxidation occurred via the mitochondrial aldehyde dehydrogenase, and part via formaldehyde dehydrogenase. The fact that inhibition by crotonaldehyde is competitive may be of value since other commonly used inhibitors of aldehyde dehydrogenase are irreversible inhibitors of the enzyme.

Acetaldehyde↗
PubMed1984

Effect of acetaldehyde and cyanamide on the metabolism of formaldehyde by hepatocytes, mitochondria, and soluble supernatant from rat liver.

Formaldehyde can be metabolized primarily by two different pathways, one involving oxidation by the low-Km mitochondrial aldehyde dehydrogenase, the other involving a specific, glutathione-dependent, formaldehyde dehydrogenase. To estimate the roles played by each enzyme in formaldehyde metabolism by rat hepatocytes, experiments with acetaldehyde and cyanamide, a potent inhibitor of the low-Km aldehyde dehydrogenase were carried out. The glutathione-dependent oxidation of formaldehyde by 100,000g rat liver supernatant fractions was not affected by either acetaldehyde or by cyanamide. By contrast, the uptake of formaldehyde by intact mitochondria was inhibited 75 to 90% by cyanamide. Acetaldehyde inhibited the uptake of formaldehyde by mitochondria in a competitive fashion. Formaldehyde was a weak inhibitor of the oxidation of acetaldehyde by mitochondria, suggesting that, relative to formaldehyde, acetaldehyde was a preferred substrate. In isolated hepatocytes, cyanamide, which inhibited the oxidation of acetaldehyde by 75 to 90%, produced only 30 to 50% inhibition of formaldehyde uptake by cells as well as of the production of 14CO2 and of formate from [14C]formaldehyde. The extent of inhibition by cyanamide was the same as that produced by acetaldehyde (30-40%). In the presence of cyanamide, acetaldehyde was no longer inhibitory, suggesting that acetaldehyde and cyanamide may act at the same site(s) and inhibit the same formaldehyde-oxidizing enzyme system. These results suggest that, in rat hepatocytes, formaldehyde is oxidized by cyanamide- and acetaldehyde-sensitive (low-Km aldehyde dehydrogenase) and insensitive (formaldehyde dehydrogenase) reactions, and that both enzymes appear to contribute about equally toward the overall metabolism of formaldehyde.

Acetaldehyde↗
PubMed1984

The role of iron chelates in hydroxyl radical production by rat liver microsomes, NADPH-cytochrome P-450 reductase and xanthine oxidase.

Uninduced rat liver microsomes and NADPH-Cytochrome P-450 reductase, purified from phenobarbital-treated rats, catalyzed an NADPH-dependent oxidation of hydroxyl radical scavenging agents. This oxidation was not stimulated by the addition of ferric ammonium sulfate, ferric citrate, or ferric-adenine nucleotide (AMP, ADP, ATP) chelates. Striking stimulation was observed when ferric-EDTA or ferric-diethylenetriamine pentaacetic acid (DTPA) was added. The iron-EDTA and iron-DTPA chelates, but not unchelated iron, iron-citrate or iron-nucleotide chelates, stimulated the oxidation of NADPH by the reductase in the absence as well as in the presence of phenobarbital-inducible cytochrome P-450. Thus, the iron chelates which promoted NADPH oxidation by the reductase were the only chelates which stimulated oxidation of hydroxyl radical scavengers by reductase and microsomes. The oxidation of aminopyrine, a typical drug substrate, was slightly stimulated by the addition of iron-EDTA or iron-DTPA to the microsomes. Catalase inhibited potently the oxidation of scavengers under all conditions, suggesting that H2O2 was the precursor of the hydroxyl radical in these systems. Very high amounts of superoxide dismutase had little effect on the iron-EDTA-stimulated rate of scavenger oxidation, whereas the iron-DTPA-stimulated rate was inhibited by 30 or 50% in microsomes or reductase, respectively. This suggests that the iron-EDTA and iron-DTPA chelates can be reduced directly by the reductase to the ferrous chelates, which subsequently interact with H2O2 in a Fenton-type reaction. Results with the reductase and microsomal systems should be contrasted with results found when the oxidation of hypoxanthine by xanthine oxidase was utilized to catalyze the production of hydroxyl radicals. In the xanthine oxidase system, ferric-ATP and -DTPA stimulated oxidation of scavengers by six- to eightfold, while ferric-EDTA stimulated 25-fold. Ferric-desferrioxamine consistently was inhibitory. Superoxide dismutase produced 79 to 86% inhibition in the absence or presence of iron, indicating an iron-catalyzed Haber-Weiss-type of reaction was responsible for oxidation of scavengers by the xanthine oxidase system. These results indicate that the ability of iron to promote hydroxyl radical production and the role that superoxide plays as a reductant of iron depends on the nature of the system as well as the chelating agent employed.

Animals↗
PubMed1983

Production of formaldehyde and acetone by hydroxyl-radical generating systems during the metabolism of tertiary butyl alcohol.

t-Butyl alcohol is not a substrate for alcohol dehydrogenase or for the peroxidatic activity of catalase and, therefore, it is used frequently as an example of a non-metabolizable alcohol. t-Butyl alcohol is, however, a scavenger of the hydroxyl radical. The current report demonstrates that t-butyl alcohol can be oxidized to formaldehyde plus acetone by hydroxyl radicals generated from four different systems. The systems studied were: (a) two chemical systems, namely, the iron catalyzed oxidation of ascorbic acid and the Fenton reaction between H2O2 and iron; (b) an enzymatic system, the coupled oxidation of xanthine by xanthine oxidase; and (c) a membrane-bound system, NADPH-dependent microsomal electron transfer. The oxidation of t-butyl alcohol appeared to be mediated by hydroxyl radicals, or by a species with the oxidizing power of the hydroxyl radical, because the production of formaldehyde plus acetone was (a) inhibited by competing scavengers of the hydroxyl radical; (b) stimulated by the addition of iron-EDTA; and (c) inhibited by catalase. The last observation suggests that H2O2 served as the precursor of the hydroxyl radical in all three systems. A possible mechanism is hydrogen abstraction to form the alkoxyl radical [CH3)3-C-O.), spontaneous fission of the alkoxyl radical to produce acetone and the methyl radical (CH3.), interaction of the methyl radical with O2 to form the methyl peroxy radical (CH300.), and decomposition of the later to formaldehyde. These results extend the alcohol oxidizing capacity of the microsomal alcohol oxidizing system to a tertiary alcohol. Since t-butyl alcohol is not a substrate for alcohol dehydrogenase or catalase, the ability of microsomes to oxidize t-butyl alcohol lends further support for a role for hydroxyl radicals in the microsomal alcohol oxidation system. In view of the production of formaldehyde, and the reactivity as well as further metabolism of this aldehyde, caution should be used in interpreting experiments in which t-butyl alcohol is used as a presumed "non-metabolizable" alcohol. t-Butyl alcohol may be a valuable probe for the detection of hydroxyl radicals in intact cells and in vivo.

Acetone↗
PubMed1983

The generation of hydroxyl and alkoxyl radicals from the interaction of ferrous bipyridyl with peroxides.

Reaction conditions by which the iron-chelate ferrous bipyridyl can be used as a Fenton reagent to generate specifically alkoxyl radical (.OR) from its corresponding alkyl hydroperoxide (ROOH) without producing hydroxyl radical (.OH) as a result of autoxidation are described. In this manner, the relative ability of common .OH-scavenging agents to react with .OH and various .OR species could be assessed. When .OH was generated from H2O2, 4-methylmercapto-2-oxobutyrate, ethanol and benzoate all were oxidized. When .OR (cumoxyl radical, t-butoxyl radical or ethoxyl radical) was generated specifically, each was found to oxidize 4-methylmercapto-2-oxobutyrate and ethanol. In contrast with .OH, however, none of the .OR radicals mediated the decarboxylation of benzoate. Cross-competition studies with the scavengers showed that, in contrast with the .OH-dependent reaction, the .OR-dependent oxidation of 4-methylmercapto-2-oxobutyrate and ethanol was not inhibited by benzoate. Rate constants for ferrous bipyridyl oxidation by ROOH and by H2O2 were found to be essentially the same, and therefore the differential oxidation of the various scavengers was not a reflection of iron-peroxide interaction, but rather an interaction between generated oxy radicals and the scavengers. In contrast with the H2O2 system, catalase did not inhibit the oxidation of 4-methylmercapto-2-oxobutyrate or ethanol by either the cumene hydroperoxide or the t-butyl hydroperoxide system, suggesting that the oxidizing species was not derived from H2O2. These results suggest that benzoate decarboxylation might serve as a more specific probe to detect the presence of .OH than either 4-methylmercapto-2-oxobutyrate or ethanol, which react readily with .OR.

Benzoates↗
PubMed1983

The effect of EDTA and iron on the oxidation of hydroxyl radical scavenging agents and ethanol by rat liver microsomes.

Rat liver microsomes catalyzed an NADPH-dependent oxidation of dimethylsulfoxide, 2-keto-4-thiomethylbutyrate and ethanol. The addition of EDTA and iron (ferric)-EDTA increased the oxidation of the hydroxyl radical scavenging agents and ethanol. Unchelated iron had no effect; therefore, appropriately chelated iron is required to stimulate microsomal production of hydroxyl radicals. Catalase strongly inhibited control rates as well as EDTA or iron-EDTA stimulated rates of hydroxyl radical production whereas superoxide dismutase had no effect. The rate of ethanol oxidation was ten- to twenty-fold greater than the rate of oxidation of hydroxyl radical scavengers in the absence of EDTA or iron-EDTA, suggesting little contribution by hydroxyl radicals in the pathway of ethanol oxidation. In the presence of EDTA or iron-EDTA, the rate of ethanol oxidation increased, and under these conditions, hydroxyl radicals appear to play a more significant role in contributing toward the overall oxidation of ethanol.

Animals↗
PubMed1983

NADPH-dependent production of oxy radicals by purified components of the rat liver mixed function oxidase system. I. Oxidation of hydroxyl radical scavenging agents.

Isolated microsomes catalyze an NADPH-dependent oxidation of typical hydroxyl radical scavenging agents. To determine which microsomal components participate in the oxidation of the scavengers, experiments were carried out with purified NADPH-cytochrome P-450 reductase and cytochrome P-450 isolated from phenobarbital-treated rats. The production of ethylene from 4-ketothiomethylbutyrate or of formaldehyde from either dimethyl sulfoxide or tertiary butyl alcohol was measured in the presence of NADPH plus reductase or NADPH plus reductase plus cytochrome P-450. The reductase-dependent system itself catalyzed the oxidation of the three scavengers. Addition of cytochrome P-450 had no effect on the rates of oxidation of the scavengers. Relative rates of oxidation of the scavengers reflected the amount of the reductase in the assay system. Varying the amount of cytochrome P-450 at a fixed concentration of the reductase did not result in rates different from that observed in the absence of cytochrome P-450. Dilauroyl phosphatidylcholine appeared to have a stimulatory role in these oxidations, whereas cytochrome P-450 reductase and NADPH were obligatory components. The reductase-dependent oxidation of the scavengers was inhibited by superoxide dismutase, catalase, and competing hydroxyl radical scavenging agents suggesting that superoxide, hydrogen peroxide, and an oxygen radical with the oxidizing power of the hydroxyl radical played a role in these oxidations. Further, these oxidations were inhibited by the iron-chelator desferrioxamine but stimulated by either EDTA or by iron. These results suggest that an iron-catalyzed Haber-Weiss reaction might be involved in the mechanism by which purified cytochrome P-450 reductase mediates the oxidation of typical hydroxyl radical scavengers. The results demonstrated that NADPH-cytochrome P-450 reductase may represent an important locus of oxygen activation leading to the production of a highly oxidizing species characteristic of the hydroxyl radical.

Animals↗
PubMed1983

Inhibition of microsomal oxidation of alcohols and of hydroxyl-radical-scavenging agents by the iron-chelating agent desferrioxamine.

Rat liver microsomes (microsomal fractions) catalyse the oxidation of straight-chain aliphatic alcohols and of hydroxyl-radical-scavenging agents during NADPH-dependent electron transfer. The iron-chelating agent desferrioxamine, which blocks the generation of hydroxyl radicals in other systems, was found to inhibit the following microsomal reactions: production of formaldehyde from either dimethyl sulphoxide or 2-methylpropan-2-ol (t-butylalcohol); generation of ethylene from 4-oxothiomethylbutyric acid; release of 14CO2 from [I-14C]benzoate; production of acetaldehyde from ethanol or butanal (butyraldehyde) from butan-1-ol. Desferrioxamine also blocked the increase in the oxidation of all these substrates produced by the addition of iron-EDTA to the microsomes. Desferrioxamine had no effect on a typical mixed-function-oxidase activity, the N-demethylation of aminopyrine, nor on the peroxidatic activity of catalase/H2O2 with ethanol. H2O2 appears to be the precursor of the oxidizing radical responsible for the oxidation of the alcohols and the other hydroxyl-radical scavengers. Chelation of microsomal iron by desferrioxamine most likely decreases the generation of hydroxyl radicals, which results in an inhibition of the oxidation of the alcohols and the hydroxyl-radical scavengers. Whereas desferrioxamine inhibited the oxidation of 2-methylpropan-2-ol, dimethyl sulphoxide, 4-oxothiomethylbutyrate and benzoate by more than 90%, the oxidation of ethanol and butanol could not be decreased by more than 45-60%. Higher concentrations of desferrioxamine were required to block the metabolism of the primary alcohols than to inhibit the metabolism of the other substrates. The desferrioxamine-insensitive rate of oxidation of ethanol was not inhibited by competitive hydroxyl-radical scavengers. These results suggest that primary alcohols may be oxidized by two pathways in microsomes, one dependent on the interaction of the alcohols with hydroxyl radicals (desferrioxamine-sensitive), the other which appears to be independent of these radicals (desferrioxamine-insensitive).

Alcohols↗
PubMed1983

Organic hydroperoxide-dependent oxidation of ethanol by microsomes: lack of a role for free hydroxyl radicals.

Organic hydroperoxides can replace NADPH in supporting the oxidation of ethanol by liver microsomes. Experiments were carried out to evaluate the role of hydroxyl radicals in the organic hydroperoxide-catalyzed reaction. Maximum rates of ethanol oxidation occurred in the presence of either 0.5 mM cumene hydroperoxide or 2.5 mM t-butyl hydroperoxide and were linear for 2 to 4 min. The Km for ethanol was about 12 mM and Vmax was about 8 nmol ethanol oxidized/min/mg microsomal protein. Besides ethanol, the organic hydroperoxides supported the oxidation of longer-chain alcohols (1-butanol), and secondary alcohols (isopropanol). The organic hydroperoxide-supported oxidation of alcohols was not affected by several hydroxyl-radical scavengers such as dimethylsulfoxide, mannitol, or 2-keto-4-thiomethylbutyrate which blocked NADPH-dependent oxidation of alcohols by 50% or more. Iron-EDTA, which increases the production of hydroxyl radicals, increased the NADPH-dependent oxidation of ethanol, whereas desferrioxamine, which blocks the production of hydroxyl radicals, inhibited the NADPH-dependent oxidation of ethanol. Neither iron-EDTA nor desferrioxamine had any effect on the organic hydroperoxide-supported oxidation of ethanol. Cumene-and t-butyl hydroperoxide did not support microsomal oxidation of hydroxyl-radical scavengers. These results suggest that, in contrast to the NADPH-dependent oxidation of ethanol, free-hydroxyl radicals do not play a role in the organic hydroperoxide-dependent oxidation of ethanol by microsomes. Ethanol appears to be oxidized by two pathways in microsomes, one which is dependent on hydroxyl radicals, and the other which appears to be independent of these oxygen radicals.

1-Butanol↗
PubMed1983

Increased microsomal oxidation of hydroxyl radical scavenging agents and ethanol after chronic consumption of ethanol.

The oxidation of ethanol by rat liver microsomes is increased after chronic ethanol consumption. Previous experiments indicated that hydroxyl radicals play a role in the mechanism whereby microsomes oxidize ethanol. Experiments were therefore carried out to evaluate the role of these radicals in ethanol oxidation by microsomes from ethanol-fed rats, and to determine whether the increase in ethanol oxidation by these induced microsomes correlates with an increase in the generation of hydroxyl radicals. Rat liver microsomes from ethanol-fed rats catalyzed the oxidation of two typical hydroxyl radical scavenging agents, dimethylsulfoxide and 2-keto-4-thiomethylbutyric acid, at rates which were two- to threefold greater than rates found with control microsomes. This increased rate of oxidation of hydroxyl radical scavengers was similar to the increased rate of microsomal oxidation of ethanol. Azide, which inhibits contaminating catalase in microsomes, increased the oxidation of dimethyl sulfoxide and 2-keto-4-thiomethylbutyric acid by both microsomal preparations. This suggests that H2O2 may serve as the microsomal precursor of the hydroxyl radical. Cross competition for oxidation between ethanol and the hydroxyl radical scavenging agents was observed. Moreover, the oxidation of ethanol, dimethyl sulfoxide, or 2-keto-4-thiomethylbutyric acid was inhibited by other compounds which interact with hydroxyl radicals, e.g., benzoate, and the free-radical, spin-trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide. These results suggest that the increase in the rate of ethanol oxidation found with microsomes from ethanol-fed rats may be due, at least in part, to an increase in the rate of production of hydroxyl radicals by these induced microsomes. Increased production of oxyradicals may possibly result in oxidative damage to the liver cell as a result of ethanol consumption.

Alcoholism↗
PubMed1983

Evidence for two ethanol oxidizing pathways in reconstituted mixed-function oxidase systems.

The oxidation of ethanol and typical hydroxyl radical scavengers by NADPH-cytochrome P-450 reductase and cytochrome P-450 purified from phenobarbital-treated rats were studied. Ethanol and the scavengers could be oxidized by the reductase system itself. This system was inhibited by superoxide dismutase, competing hydroxyl radical scavengers and desferrioxamine, but stimulated by either EDTA or iron. These results suggest that an iron-catalyzed Haber-Weiss reaction might be involved in the mechanism by which the reductase mediates the oxidation of typical hydroxyl radical scavengers and ethanol. The addition of cytochrome P-450 had no effect on the oxidation of the scavengers, whereas the oxidation of ethanol was enhanced two-to three-fold over the reductase-dependent rate. The oxidation of ethanol was dependent on both the amount of reductase and P-450. There was no effect of competing scavengers, superoxide dismutase or desferrioxamine on the increased rate of ethanol oxidation produced upon addition of cytochrome P-450. Organic hydroperoxides supported the oxidation of ethanol, but not that of the scavengers when added directly to cytochrome P-450. These results suggest that two independent pathways are operative in supporting NADPH-dependent microsomal oxidation of ethanol. One pathway involves hydroxyl radicals which can be generated by the reductase, whereas the other pathway requires the combined presence of both the reductase and cytochrome P-450, and appears to be independent of oxygen radicals.

Animals↗
PubMed1983

Effect of ethanol and metabolic substrates on the oxidation of aminopyrine, formaldehyde and formate by isolated hepatocytes.

The production of [14C]O2 from 14C-labeled aminopyrine involves the following sequence: Aminopyrine 1 leads to formaldehyde 2 leads to formate 3 leads to CO2 Ethanol has the potential to affect any of the above steps in this sequence. In isolated hepatocytes from fasted rats ethanol inhibited CO2 production from aminopyrine, but not from formaldehyde or formate. Significant inhibition was found at low levels of ethanol that do not affect aminopyrine metabolism by isolated microsomes. There was only a slight accumulation of formaldehyde and formate during the oxidation of aminopyrine to CO2, both in the absence or presence of ethanol. This suggests that step I is the rate-limiting step and the step most sensitive to ethanol. There was accumulation of formate during the oxidation of formaldehyde to CO2. Ethanol decreased this formate accumulation suggesting some inhibition of the overall rate of formaldehyde oxidation. Addition of pyruvate, lactate, fructose, xylitol and sorbitol increased the rate of CO2 production from aminopyrine, but not from formaldehyde or formate. This increase by the substrates is probably due to an increase in the availability of NADPH required for step I. There was a slight increase in the accumulation of formaldehyde or formate during the oxidation of aminopyrine to CO2 in the presence of the substrates. Pyruvate and fructose nearly completely prevented the inhibition of CO2 production from aminopyrine by ethanol. Partial prevention was noted with the other substrates. Reduction of the cellular redox state as a consequence of ethanol metabolism may interfere with the transport of NADPH out of the mitochondria and, consequently, decrease the availability of NADPH for step I.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗