Oxidation of Ethanol in the and Its Consequences

Richard Deitrich, Ph.D.; Sergey Zimatkin, M.D., Ph.D.; and Sergey Pronko, M.D., Ph.D.

Acetaldehyde, a toxic byproduct of (i.e., ethanol) metabolism, has long been suspected of causing at least some of the central nervous system actions of ethanol. However, the data to support such a hypothesis have been difficult to obtain. One roadblock is the very low blood levels of acetaldehyde following ethanol intake and the finding that even elevated acetaldehyde levels in the blood do not easily gain access to the brain. The recent discovery of the oxidation of ethanol to acetaldehyde in the adult brain may help explain the acute effects of ethanol. KEY WORDS: Ethanol metabolism; ethanol-to-acetaldehyde metabolism; acetaldehyde; acetate; aldehyde dehydrogenase (ALDH); central nervous system; brain; catalase; cytochrome P450; alcohol dehydrogenase (ADH); ethanol oxidation; behavior; ethanol preference

his article reviews studies of a Heap et al. 1995). However, several (i.e., aldehyde dehydrogenase [ALDH]) potential role for acetaldehyde, factors cast doubt on this hypothesis. in the blood–brain barrier, which may Ta toxic byproduct of alcohol First, avid metabolism of acetaldehyde help keep brain acetaldehyde levels low (i.e., ethanol) metabolism, in ethanol’s by the liver keeps blood levels of (Petersen 1985; Tampier et al. 1993). effects in the central nervous system acetaldehyde following ethanol inges- Third, although one could use the (CNS); the metabolism of ethanol to tion extremely low (Sippel and Eriksson compound pyrazole to inhibit the reac­ acetaldehyde in the brain; the metabolism 1975). The levels of acetaldehyde in tion by which the enzyme alcohol of acetaldehyde in brain cells; the results most people after ethanol ingestion are dehydrogenase (ADH) breaks down of ethanol oxidation to form acetalde- nearly undetectable in the blood, on ethanol (i.e., oxidation), and thus hyde; and acetaldehyde’s effects on the order of one micromole.1 Second, inhibit the formation of acetaldehyde, behavior. The studies cited primarily even if the blood acetaldehyde levels intoxication still would result, suggesting are those dealing with acute or very are significant, either because of genetic that acetaldehyde does not play a sig­ short-term administration of ethanol. variation in alcohol-metabolizing nificant role in ethanol’s effects on the The role of acetaldehyde in tolerance enzymes or the presence of drugs that brain. Indeed, Goldstein and Zaechelein and dependence or in the peripheral allow build-up of acetaldehyde, (1983) used pyrazole to study intoxica­ effects of ethanol is not covered. acetaldehyde does not seem to be able to penetrate blood vessels into the brain (i.e., the blood–brain barrier), and sub- RICHARD DEITRICH, PH.D., is a professor Acetaldehyde’s Role in stantial blood levels are required before emeritus, Department of Pharmacology, Ethanol’s Effects acetaldehyde levels increase in the brain University of Colorado, Aurora, Colorado. (Tabakoff et al. 1976; Westcott et al. Acetaldehyde, a toxic byproduct of 1980; Sippel 1974; Zimatkin and SERGEY ZIMATKIN, M.D., PH.D., ethanol metabolism, may be at least Pronko 1995). This is attributed pri­ is a professor, Grodno State Medical partially responsible for ethanol’s actions marily to the presence of the enzyme University, Grodno, Belarus. in the CNS (Hunt 1996; Hashimoto that converts acetaldehyde to acetate et al. 1989; Bergamaschi et al. 1988; SERGEY PRONKO, M.D., PH.D., is a

Zimatkin and Deitrich 1997; Thadani 1 A micromole represents a concentration of 1/1,000,000 fellow, Department of Pharmacology, and Truitt 1977; Collins et al. 1988; (one millionth) molecular weight per liter (mol/L). University of Colorado, Aurora, Colorado.

266 Alcohol Research & Health Consequences of Ethanol Oxidation in the Brain

tion in mice using a vapor chamber ethanol in rat brain tissue. In both studies, et al. 1999). In addition, a recent study method. In this method, the metabolism inhibitors of catalase also were effective in rats and mice has reinforced the pos­ of inhaled ethanol is slowed, providing in inhibiting the production of acetalde­ sibility that cytochrome P450 is involved for more prolonged and consistent blood hyde. On the other hand, inhibitors of in the brain’s metabolism of ethanol levels of ethanol, producing physical the enzymes cytochrome P450 and (Zimatkin et al. 2006). dependence in mice. ADH—key enzymes involved in alcohol metabolism— were ineffective. Other ADH. The possible role of ADH in Metabolism of Ethanol to investigators quickly confirmed these the metabolism of ethanol in the brain Acetaldehyde in the Brain findings (Hamby-Mason et al. 1997; remains unclear. Research originally Aspberg et al. 1993; Zimatkin et al. suggested that only the subtype ADH3 These considerations would be irrele­ 1999). In studies of cells from all parts was expressed in the brain and that vant if the brain could produce its own ethanol was not a good candidate for acetaldehyde from ethanol. Although that enzyme to act on (i.e., it was a poor there had been several reports of the substrate) (Beisswenger et al. 1985; oxidation of ethanol in the brain Kerr et al. 1989). Several groups (Kerr (Sutherland et al. 1958; Raskin 1973; The role of et al. 1989; Buhler et al. 1983) reported Raskin and Sokoloff 1974; Raskin and the presence of ADH1 in brain cells. Sokoloff 1968; Raskin and Sokoloff ADH in the Giri and colleagues (1989) found 1970a, b; Raskin and Sokoloff 1972a, metabolism of ADH3 expressed in rat brain, and b), this idea largely was dismissed by Martinez and colleagues (2001) found the findings of Mukherji and colleagues ethanol in the brain mRNA for ADH1 and ADH4 in rat (1975), whose studies showed that brain cells. Although the authors could ethanol did not break down to acetalde­ remains unclear. not demonstrate ADH activity in anal­ hyde in the brain. ysis of whole-brain homogenates, they were able to detect ADH activity in Catalase. Catalase, the enzyme that specific neurons (i.e., granular cells and facilitates the breakdown of hydrogen of the brain (i.e., whole-brain Purkinje cells) of the cerebellum. This peroxide to oxygen and water, may play homogenates), the intensity of ethanol shows that although the activity of a role in the production of acetaldehyde oxidation is comparatively low but may ADH may be undetectable in whole from ethanol in the brain. Cohen and be much higher in the specific struc­ homogenates, there may be sufficient colleagues (1980) demonstrated that tures and cells known for their activity in specific neurons to form catalase in conjunction with hydrogen increased catalase activity (Zimatkin acetaldehyde locally. peroxide will oxidize ethanol in the and Lindros 1996). brain. Although the authors did not directly demonstrate the production of Cytochrome P450. Cytochrome P450 The Chemical Reactions acetaldehyde (and thus the metabolism enzymes, which are involved in ethanol Allowing Oxidation of of ethanol), in this system, they did metabolism in the liver, have been impli­ Ethanol to Acetaldehyde provide impetus to other investigators’ cated in the metabolism of ethanol in attempts. Researchers initially were the brain. First, Warner and Gustafsson The oxidation of ethanol produces thwarted in their attempts to document (1994) demonstrated the presence of acetaldehyde (see Figure). The production metabolism of ethanol in the brain when cytochrome P450 in rat brain and its of acetaldehyde by catalase is limited they discovered nonenzymatic (i.e., induction by ethanol. Cytochrome P450 by the availability of hydrogen perox­ artifactual) production of acetaldehyde. 2E1, a variant of cytochrome P450 ide, a potentially harmful byproduct of It was determined that the iron typically (i.e., isozyme) that is capable of oxidiz­ ethanol metabolism by cytochrome found in red blood cells (i.e., hemoglobin) ing ethanol efficiently in other tissues, P450. Hydrogen peroxide also can caused this nonenzymatic formation of also was found in the brain (Hansson come from a number of other sources, acetaldehyde from ethanol, thus mask­ et al. 1990). Its , messenger RNA including the enzyme monoamine oxi­ ing any enzymatic production of (mRNA), specific activity, and induc­ dase, ascorbic acid (vitamin C), and acetaldehyde. Two groups, nearly tion by ethanol were found in nerve other cytochrome P450 oxidations simultaneously, overcame these problems. cells (i.e., neurons) and support cells (Sandri et al. 1990; Simonson et al. Aragon and colleagues (1992) demon­ (i.e., glial cells) in the following brain 1993; Sinet et al. 1980). strated that acetaldehyde was produced regions: cerebellum, cerebral cortex, All studies of the oxidation of ethanol from ethanol in rat with all blood thalamus, and hippocampus (Sohda to acetaldehyde depend on the ability removed. Gill and colleagues (1992) et al. 1993; Tindberg and Ingelman- to measure the accumulation of were able to prevent the artifactual for­ Sundberg 1996; Upadhya et al. 2000). acetaldehyde. This can occur only if mation of acetaldehyde and show the Cytochrome P450 also has been found the rate of removal of acetaldehyde is production of acetaldehyde from in prenatal human brain cells (Khalighi slower than its rate of formation in the

Vol. 29, No. 4, 2006 267 (Carmichael et al. 1991; Cullen and Carlen 1992; Correa et al. 2003). Thus, administering sodium acetate in doses comparable with those observed after administering 1 to 2 g/kg ethanol pro­ duced a dose-dependent impairment of motor coordination (Carmichael et al. 1991). Because acetate’s effects can be blocked with the use of 8-phenyltheo­ phylline, a substance that blocks recep­ tors for adenosine (a byproduct in acetate breakdown), it has been sug­ gested that acetate’s actions may be mediated by adenosine (Carmichael et Figure Pathways of ethanol metabolism in the brain. The oxidation of ethanol produces acetaldehyde. The production of acetaldehyde by the al. 1991; Cullen and Carlen 1992). enzyme catalase (found in internal cell components called peroxi­ Moreover, administering low doses of

somes) requires hydrogen peroxide (H2O2). The enzyme cytochrome acetate (0.35 to 2.8 micromolar) by P4502E1 is present in brain cell structures in the smooth endoplasmic injection into the brain through a small reticulum (microsomes). Alcohol dehydrogenase (ADH) is an enzyme hole bored into the skull (i.e., intrac­ found in the cell’s fluid or . The enzyme aldehyde dehydroge­ erebroventricular [ICV] administration) nase (ALDH), found in the cell’s mitochondria and cytosol, converts produced a potent decrease in motor acetaldehyde to acetate. activity, similar to the effects of ethanol and acetaldehyde on motor activity system under study. Substantial amounts 2 (Correa et al. 2003). (i.e., a low Km) and rate of enzyme of acetaldehyde are oxidized to acetate activity with acetaldehyde and is suffi­ in these in vitro systems. This results in cient to remove most of the acetalde­ Consequences of the an underestimation of the rate of ethanol hyde. Several other forms of ALDH are metabolism in the brain, because Oxidation of Ethanol expressed in brain cells as well (Sophos to Acetaldehyde acetaldehyde is metabolized to acetate and Vasiliou 2003). The localization of nearly as quickly as it is formed. Thus, the enzyme to specific cells or areas of Ethanol oxidation to acetaldehyde has only the net amount of acetaldehyde in the brain could greatly influence the several consequences, which may be the system is accounted for when only local rate of removal of acetaldehyde. broken down into two broad categories. acetaldehyde accumulation is measured. That is, acetaldehyde is only metabo­ The first is the direct binding of acetalde­ Studies of the oxidation of ethanol to lized if it is present in an area of the hyde to (Jennett et al. 1987; acetaldehyde in the brain therefore brain that also has ALDH enzymes McKinnon et al. 1987; Nakamura et need to consider these limitations. (Zimatkin et al. 1992). In a similar al. 2003; Zimatkin et al. 1992), nucleic fashion, localization within the cell of acids (Wang et al. 2000), and a type of Metabolism of Acetaldehyde the enzymes responsible for the pro­ fat (i.e., ) containing phosphorus in Brain Cells duction of acetaldehyde (catalase in (i.e., ) (Trudell et al. 1990, internal cell components called peroxi­ 1991; Trudell et al. 1990; Kenney 1982, The metabolism of acetaldehyde in the somes and cytochrome P450 in a net­ 1984). In total, the binding to these brain is much less controversial than work of membranes within the cell cellular components probably accounts the metabolism of ethanol because called the or for very little of the acetaldehyde that ALDH enzymes have long been known microsomes) and the enzyme of acetalde­ disappears, but the consequences of to be present in brain cells (Deitrich hyde removal—ALDH2 in the mito­ these interactions may be highly signif­ 1966; Erwin and Deitrich 1966). The chondria—leave space and time for icant because the function of these cel­ ALDH enzyme most likely to be acetaldehyde to interact with other cel­ lular components can be compromised responsible for the majority of the oxi­ lular elements before being converted by this binding. The second category dation of acetaldehyde to acetate is to acetate. That is, if acetaldehyde is of ethanol oxidation consequences is ALDH2, the form found in the mito­ produced in separate cellular structures indirect action. This occurs when the chondria, an internal component of the from where it is removed, it can have an metabolism of other aldehydes that cell. This enzyme has a high affinity effect on the cell before it is metabolized. originate in the body (i.e., endogenous Acetaldehyde’s conversion to acetate aldehydes) is inhibited through the 2 Km is a measurement used to describe the activity of an has further implications for the cell. presence of acetaldehyde. The aldehy­ enzyme. It describes the concentration of the substance upon which an enzyme acts at which the enzyme works Acetate has significant CNS effects des produced by the oxidation, by at 50 percent capacity. that are separate from those of ethanol monoamine oxidase, of the brain chem-

268 Alcohol Research & Health Consequences of Ethanol Oxidation in the Brain icals (i.e., neurotransmitters) dopamine, Acetaldehyde has been measured and ethanol preference. Although none norepinephrine, and serotonin, are par­ directly in the brain in only a few stud­ of the studies below included direct ticularly vulnerable to this reaction ies (Jamal et al. 2003, 2004, 2005). In measurements of brain ethanol oxida­ (Deitrich and Erwin 1980). One theory those studies, ALDH was inhibited, tion in vitro, brain acetaldehyde levels is that acetaldehyde or the aldehydes resulting in relatively high levels of in vivo, or acetaldehyde accumulation of dopamine, norepinephrine, or acetaldehyde in the brain. It is assumed in vitro, their findings do offer some epinephrine condense with these same that the proximal cause of these behav­ implications regarding the relationship neurotransmitters to produce compounds ioral effects (such as ataxia or loss of between brain acetaldehyde and ethanol called tetrahydroisoquinolines that may the righting response) is the altered preference. be responsible for some of ethanol’s amount of acetaldehyde in the brains As discussed previously, catalase plays CNS effects themselves. Acetaldehyde of the animals studied. a role in the production of acetaldehyde also may condense with serotonin to On the other hand, mice with about in the brain. The catalase inhibitor form compounds called tetrahydro-beta half the usual levels of catalase in the aminotriazole attenuated ethanol pref­ carbolines that may be active in the brain brain (i.e., acatalasemic mice), which erence in mice (Koechling and Amit as well. Thus, these amine-aldehyde should have less acetaldehyde from 1994), suggesting that inhibiting cata­ condensation products may be respon­ ethanol in the brain compared with lase results in decreased levels of sible for some of the behavioral actions control mice, had longer sleep times acetaldehyde and a decline in this of ethanol (Davis and Walsh 1970; after ethanol intake than control mice particular ethanol-induced behavior. Cohen and Collins 1970; Melchior and (Aragon and Amit 1993; Vasiliou et al. Consistent with these findings, Amit Myers 1977). Considerable controversy 2004). This suggests that acetaldehyde and Aragon (1988) found that blood arose around this theory, especially does not influence ethanol-induced sleep catalase from rats naïve to ethanol corre­ because these compounds occur natu­ times. Similar results were obtained using lated positively with ethanol preference rally in the diet, casting doubt on the mice that had been genetically modified in the animals (blood and brain cata­ relevance of their presence following to have the ethanol-metabolizing enzyme lase also correlated positively after ethanol ingestion (Collins et al. 1990). CYP2E1 absent. The mice exhibited exposure to ethanol). Increased catalase Researchers recently have proposed longer ethanol-induced sleep times, presumably would mean an increased that acetaldehyde may compete with especially at higher ethanol doses; they rate of production and increased brain malondialdehyde or 4-hydroxynonenal, also produced lower amounts of acetalde­ levels of acetaldehyde with resultant the aldehyde products that result after hyde following the incubation of increases in preference. Similar studies the breakdown of (i.e., lipid per- ethanol with brain cell structures con­ have found that catalase correlates with oxidation). These aldehydes also may taining ethanol-metabolizing enzymes alcohol intake in humans as well inhibit the activity of ALDHs (Luckey (i.e., microsomes) compared with con­ (Koechling and Amit 1992). et al. 1999; Mark et al. 1997; Meyer et al. trol animals (Vasiliou et al 2004). In ALDH in the brain also positively 2004; Murphy et al. 2003). This would addition, induction of brain catalase correlates with ethanol preference. Indeed, result in increased levels of acetaldehyde activity resulted in decreased loss of Amir (1978) found that rats’ ethanol as well as of these toxic aldehydes. righting reflex (LORR), which is used to preference better correlated with brain The oxidation of ethanol to acetalde­ estimate hypnotic sensitivity (a behav­ ALDH than with liver ALDH. This hyde may trigger various reactions that ioral response) to ethanol, whereas would support the idea that blood lev­ ultimately have behavior-related conse­ reduced brain catalase activity resulted els of acetaldehyde (produced in the quences, as described below. in increased LORR, showing involve­ liver) are less important to establishing ment of brain catalase in the hypnotic a preference for alcohol than brain levels effect of ethanol (Correa et al. 2001). of acetaldehyde. High blood acetalde­ Acetaldehyde and Behavior hyde levels, resulting from a genetic Ethanol Preference defect in ALDH in Asian populations, Several studies have suggested that do produce decreased ethanol intake acetaldehyde is responsible for some of Rats selectively bred to have either high (Harada et al. 1982), as does treatment the behavioral effects (such as poor or low preference for ethanol are useful with ALDH inhibitors such as disulfiram coordination [i.e., ataxia]) of ethanol animal models for the study of alcohol (Antabuse®) (Chick et al. 1992). High (reviewed in Deitrich 2004 and Querte­ consumption. Alcohol-preferring (P) ALDH activity would presumably mont et al. 2005). Many of these studies and nonpreferring (NP) rats have been indicate a lower level of brain acetalde­ measured the degree of relationship of shown to differ in hypnotic sensitivity hyde because of increased rates of oxi­ the two variables (i.e., they were correla­ to ethanol; thus, P rats are innately less dation. Higher ALDH and lower tional). That is, the studies measured the sensitive to the effects of ethanol than acetaldehyde levels are not consistent behavioral effects of ethanol following NP rats (Lumeng et al. 1982). with the positive correlation between presumed alteration of levels of acetalde­ Researchers have used P and NP catalase activity and ethanol preference. hyde in the brain by inhibiting ALDH pairs of rat lines or strains to study rela­ Also, acatalasemic mice have a higher or inhibiting or activating catalase. tionships between catalase, acetaldehyde, preference for ethanol than do control

Vol. 29, No. 4, 2006 269 mice (Aragon and Amit 1993). Vasiliou infuse ethanol and acetaldehyde directly (i.e., phospholipids) to create specific and colleagues (2006) reported that into the ventral tegmental area (VTA), physiological effects, as indicated by a acatalasemic mice accumulate only located in the midbrain. Using similar change in spectrophotometric absorption4 about 50 percent as much acetaldehyde techniques, it was found that rats would (Nilsson and Tottmar 1985). This from ethanol in vitro as control mice lever press for infusions of the conden­ shows what can happen to biogenic and that they have about half the brain sation product between acetaldehyde aldehydes if they are not oxidized by catalase activity as that in the brain of and dopamine (i.e., salsolinol) directly ALDH. When aldehydes were directly control mice. This would not totally into the nucleus accumbens, a collec­ applied to neurons, the biogenic alde­ explain the decreased ethanol metabolism tion of neurons involved in the brain’s hydes derived from dopamine and rates because catalase is not the only reward system (McBride et al. 2002). serotonin had a direct depressant effect enzyme capable of oxidizing ethanol in Arizzi and colleagues (2003) studied the on neurons in the neocortex and cere­ the brain. Previous studies on catalase in vivo effects of intracerebroventricularly bellum (Palmer et al. 1986). contribution to ethanol oxidation were administered ethanol, acetaldehyde, Many other studies of the direct performed using catalase inhibitors capa­ and acetate on lever-pressing tasks. actions of acetaldehyde are available. ble of inhibiting the activity of other These studies showed that acetaldehyde For example, large doses of acetalde­ ethanol-metabolizing enzymes (P4502E1 appears to induce activating or disin­ hyde given ICV caused decreases of and ALDH); therefore, this finding hibiting effects and thus can produce dopamine, serotonin, and a product of using genetics seems to be a more useful at least some of the effects of ethanol, dopamine metabolism (i.e., a metabo­ tool. Other researchers have conducted whereas acetate is more potent than the lite) (i.e., homovanillic acid [HVA]) extensive research that provides further other substances at producing actions and increases in a metabolite of sero­ support for the involvement of brain that lead to a suppression of lever press­ tonin (i.e., 5-hydroxyindoleacetic acid catalase in ethanol-induced behavioral ing and locomotion and thus may be [5HIAA]) in an analysis of fluid from effects. This research also supports the implicated in the motor impairments the nucleus accumbens (Ward et al. notion that acetaldehyde may be pro­ induced by ethanol. Unfortunately, the 1997). These and similar reports do duced directly in the brain by catalase researchers gave the same dose of all three not provide a consistent dataset from and that it may be an important regu­ agents in spite of the large (1,000-fold) which likely mechanisms can be deduced. lator of ethanol’s locomotor effects (for difference in their concentrations follow­ Part of the problem is that accurate example, see Sanchis-Segura et al. 1999). ing ethanol administration peripherally. measurements of acetaldehyde in the Numerous studies show the possible brain tissue have been difficult (see Acetaldehyde’s Actions in the Brain pathophysiological effects of acetalde­ Westcott et al. 1980), and so no sys­ hyde. The theories of the condensation tematic correlation of acetaldehyde Researchers also have studied the actions of acetaldehyde with biogenic amines brain levels with behavioral effects has of acetaldehyde in the brain directly, to produce new compounds are been carried out. Mascia and colleagues usually with ICV infusions of acetalde­ reviewed above. Although this reaction (2001) studied the effect of acetalde­ hyde to bypass the metabolism of certainly occurs in vivo, the importance hyde on cloned neurotransmitter recep­ acetaldehyde by the liver. Smith and of these condensation products to tors in frog oocytes. Of those studied, colleagues (1984) found that conditioned ethanol’s actions in the brain remains only a receptor for the amino acid 3 place preference could be induced by speculative. In a similar vein, acetalde­ glycine was sensitive to acetaldehyde. ICV infusions of acetaldehyde, suggest­ hyde, by substrate competitive inhibi­ In summary, research has now pro­ ing that low levels of acetaldehyde have tion of ALDH, has been postulated to vided ample evidence that ethanol is reinforcing properties. Brown and col­ cause an increase in the aldehydes derived metabolized to acetaldehyde and then leagues (1979) had found that rats would from biogenic amines (Deitrich and acetate in the brain. Several studies also administer acetaldehyde, but not ethanol, Erwin 1980). That is, ALDH can oxidize suggest that the presence of acetalde­ intracerebroventricularly. Conversely, acetaldehyde and aldehydes derived hyde in the brain is responsible for at conditioned taste aversion can be induced from biogenic amines. When acetalde­ least some of the effects of ethanol. by acetaldehyde. This action can be hyde is absent ALDH can oxidize other blocked by alpha-methyl-para-tyrosine, aldehydes. When acetaldehyde is pre­ 3 To induce conditioned place preference, an animal is a substance that inhibits the neuro­ injected with the drug being studied and is placed in a sent, acetaldehyde is bound to ALDH test chamber with distinctive environmental cues. This transmitters epinephrine (adrenaline) and is oxidized so other aldehydes are procedure is repeated for several days. During these and dopamine—key brain chemicals oxidized at a slower rate or not at all conditioning trials, the animal develops an association between the subjective state produced by the drug and involved in addiction. This indicated by ALDH. No studies have directly the environmental cues present during the drug state. that perhaps the adrenergic system is measured the purported increase in When the subject is tested in an apparatus that contains involved in acetaldehyde’s action in the these aldehydes. However, these alde­ the drug-related environmental cues in one compartment and neutral cues in another, it voluntarily moves toward brain (Aragon et al. 1991). Rodd- hydes do have suggested physiological the compartment containing the drug-related cues. Henricks and colleagues (2000, 2002) actions. For example, indole-3­ 4 Spectrophotometry is a determination of the concentra­ found that rats genetically predisposed acetaldehyde, a biogenic aldehyde, tion of a material in a sample by measurement of the to prefer alcohol would press a lever to reacts with certain substances amount of light the sample absorbs.

270 Alcohol Research & Health Consequences of Ethanol Oxidation in the Brain

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