Ocular NAD-dependent alcohol dehydrogenase and aldehyde dehydrogenase in the baboon
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ALDH2
ALDH2
Ethanol metabolism
Alcohol tolerance
ADH1B
Flushing
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ALDH2
Phosphoglycerate mutase
Ethanol metabolism
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Aldehyde dehydrogenase 2 (ALDH2) plays an important role in the cellular defense against toxic aldehydes for its ability to catalyze the oxidation of various aliphatic and aromatic aldehyde to the corresponding acids. It was reported that a high-frequency of mutant aldh2 allele (aldh2*2) existed in Asian population and the inherited deficiency of aldh2 may be the cause of the flushing syndrome and the uncomfortable effects of drinking alcohol. In this experiment, we successfully expressed ALDH2 and ALDH2*2, and identified the enzymatic activity of the two products for acetaldehyde. Their K_ms were 1.70μmol/L and 61.56 μmol/L respectively. This result supports the previous conclusion that the inherited deficiency of aldh2 is associated with the flushing syndrome and uncomfortable effects of drinking alcohol.
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Role of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Variants The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes occur in several forms that are encoded by different genes; moreover, there are variants (i.e., alleles) of some of these genes that encode enzymes with different characteristics and which have different ethnic distributions. Which ADH or ALDH alleles a person carries influence his or her level of alcohol consumption and risk of alcoholism. Researchers to date primarily have studied coding variants in the ADH1B, ADH1C, and ALDH2 genes that are associated with altered kinetic properties of the resulting enzymes. For example, certain ADH1B and ADH1C alleles encode particularly active ADH enzymes, resulting in more rapid conversion of alcohol (i.e., ethanol) to acetaldehyde; these alleles have a protective effect on the risk of alcoholism. A variant of the ALDH2 gene encodes an essentially inactive ALDH enzyme, resulting in acetaldehyde accumulation and a protective effect. It is becoming clear that noncoding variants in both ADH and ALDH genes also may influence alcohol metabolism and, consequently, alcoholism risk; the specific nature and effects of these variants still need further study. KEY WORDS: Alcohol and other drug (AOD) use (AODU), abuse and dependence; alcoholism; genetics and heredity; genetic theory of AODU; ethnic group; protective factors; ethanol metabolism; liver; alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH); risk factors; protective factors; alcohol flush reaction The effects of ingested beverage alcohol (i.e., ethanol) on different organs, including the brain, depend on the ethanol concentration achieved and the duration of exposure. Both of these variables, in turn, are affected by the absorption of ethanol into the blood stream and tissues as well as by ethanol metabolism (Hurley et al. 2002). The main site of ethanol metabolism is the liver, although some metabolism also occurs in other tissues and can cause local damage there. The main pathway of ethanol metabolism involves its conversion (i.e., oxidation) to acetaldehyde, a reaction that is mediated (i.e., catalyzed) by enzymes known as alcohol dehydrogenases (ADHs). In a second reaction catalyzed by aldehyde dehydrogenase (ALDH) enzymes, acetaldehyde is oxidized to acetate. Other enzymes, such as cytochrome P450 (e.g., CYP2E1), metabolize a small fraction of the ingested ethanol. There are multiple ADH and ALDH enzymes that are encoded by different genes (Tables 1 and 3). Some of these genes occur in several variants (i.e., alleles1), and the enzymes encoded by these alleles can differ in the rate at which they metabolize ethanol (Table 2) or acetaldehyde or in the levels at which they are produced. These variants have been shown to influence a person's drinking levels and, consequently, the risk of developing alcohol abuse or dependence (Hurley et al. 2002). Studies have shown that people carrying certain ADH and ALDH alleles are at significantly reduced risk of becoming alcohol dependent. In fact, these associations are the strongest and most widely reproduced associations of any gene with the risk of alcoholism. As will be discussed later in this article, the alleles encoding the different ADH and ALDH variants are unevenly distributed among ethnic groups. The mechanism through which ADH and ALDH variants influence alcoholism risk is thought to involve at least local elevation of acetaldehyde levels, resulting either from a more rapid ethanol oxidation (in cases of more active ADH variants) or from slower acetaldehyde oxidation (in cases of less active ALDH variants). Acetaldehyde is a toxic substance whose accumulation leads to a highly aversive reaction that includes facial flushing, nausea, and rapid heart beat (i.e., tachycardia). This reaction is similar to that experienced by alcoholics who consume alcohol after taking disulfiram (Antabuse®), a medication that discourages further drinking. …
ALDH2
ADH1B
Ethanol metabolism
Alcohol tolerance
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Summary Although mitochondrial aldehyde dehydrogenase (ALDH2) has been thought to play a major role in acetaldehyde detoxification, and the high incidence of ‘alcohol flushing’ among Orientals is attributed to the inherited deficiency of ALDH2, the role of cytosolic aldehyde dehydrogenase (ALDH1) cannot be ignored. On the premise that alcohol flushing in Caucasians could be related to ALDH1 abnormalities, we examined the enzyme properties and electrophoretic mobilities of ALDH1 partially purified from red blood cells of nine unrelated alcohol flushers. One exhibited very low activity (10–20% of control level), and another exhibited moderately low activity (60%) and altered kinetic properties. The electrophoretic mobilities of these two samples were also distinguishable from the control samples. Immunological quantitation indicated that the amounts of ALDH1 protein in these two samples were not reduced in parallel with their enzyme deficiency. In the first case, the two characteristics, i.e. very low enzyme activity and alcohol flushing, were inherited by her daughter.
ALDH2
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Aldehyde oxidase
ALDH2
ADH1B
Alcohol oxidoreductase
Alcohol tolerance
Melanogaster
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The important enzymes for alcohol metabolism included alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The metabolic pathways of alcohol were as follows: alcohol oxidized into aldehyde, and then aldehyde oxidized into acetic acid. The genetic polymorphism of ADH was composed of ADH1,ADH2(1),ADH2(2)?ADH2(3),ADH3(1)and ADH3(2). The genetic polymorphism of ALDH was composed of ALDH1,ALDH2,ALDH3 and ALDH4.
ALDH2
Ethanol metabolism
ADH1B
Alcohol Oxidation
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The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes occur in several forms that are encoded by different genes; moreover, there are variants (i.e., alleles) of some of these genes that encode enzymes with different characteristics and which have different ethnic distributions. Which ADH or ALDH alleles a person carries influence his or her level of alcohol consumption and risk of alcoholism. Researchers to date primarily have studied coding variants in the ADH1 B, ADH1C, and ALDH2 genes that are associated with altered kinetic properties of the resulting enzymes. For example, certain ADH1B and ADH1C alleles encode particularly active ADH enzymes, resulting in more rapid conversion of alcohol (i.e., ethanol) to acetaldehyde; these alleles have a protective effect on the risk of alcoholism. A variant of the ALDH2 gene encodes an essentially inactive ALDH enzyme, resulting in acetaldehyde accumulation and a protective effect. It is becoming clear that noncoding variants in both ADH and ALDH genes also may influence alcohol metabolism and, consequently, alcoholism risk; the specific nature and effects of these variants still need further study.
ADH1B
ALDH2
Ethanol metabolism
Alcohol tolerance
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We examined the genotypes of the aldehyde dehydrogenase (ALDH)‐2 , alcohol dehydrogenase (ADH)‐2, ADH3 , and P‐4502E1 loci of 53 alcoholics and 97 nonalcoholics. All of the subjects fulfilled the DSM‐III‐R criteria for alcohol dependence. The control group consisted of 97 subjects who were either hospital staff or students. We also compared the frequencies of homozygous ALDH2*1/1 and heterozygous ALDH2*1/2 genotypes in alcoholics. Our study revealed differences in the allelic frequencies of the ALDH2, ADH2 , and ADH3 loci between alcoholics and nonalcoholics. For alcoholics with both homozygous ALDH2*1/1 and heterozygous ALDH2*1/2 genotypes, it was found that ADH2 and ADH3 played important roles. Alcoholics with the heterozygous ALDH2*1/2 genotype showed a significantly higher frequency of ADH2*1/1 than ones with the homozygous ALDH2*1/1 genotype. We assume ADH2*1 plays an important role in the development of alcoholism in alcoholics with the heterozygous ALDH2*1/2 genotype.
ALDH2
Heterozygote advantage
Compound heterozygosity
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Abstract Background Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD), though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD. Methods ALDH2 genotyping was performed in 535 healthy controls and 281 patients with ALD. Results The prevalence of the common form of the single nucleotide polymorphism rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4%) compared to that of controls (73.7%, P Conclusions Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.
ALDH2
Ethanol metabolism
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