No Sex and Age Influence on the Expression Pattern and Activities of Human Gastric Alcohol and Aldehyde Dehydrogenases

Lai, Ching‐Long; Chao, You‐Chen; Chen, Yi-Chyan; Liao, Chin-Shya; Chen, Mei-Chun; Liu, Yee-Chun; Yin, and Shih-Jiun

doi:10.1097/00000374-200011000-00004

Cited by 7 publications

(10 citation statements)

References 39 publications

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“…The latter finding is consistent with the report of Vidal et al (1998). Furthermore, the activity in human stomach and colon was not influenced by sex and age (Yin et al, 1994;Lai et al, 2000). Our analysis found that the activity in human liver was similar in both sexes but slightly, although not significantly, decreased in older subjects.…”

Section: Aldh2 Gene Snps and The Metabolism Of Aldehydessupporting

confidence: 93%

Effects of Aldehyde Dehydrogenase-2 Genetic Polymorphisms on Metabolism of Structurally Different Aldehydes in Human Liver

Wang¹,

Nakajima²,

Kawamoto³

et al. 2002

Drug Metab Dispos

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This paper is available online at http://dmd.aspetjournals.org ABSTRACT:Genotype analysis of the aldehyde dehydrogenase (ALDH)-2 gene was performed using an improved simplified method, and effects of the genotype on the metabolism of a variety of aldehydes in different fractions of human liver cells were investigated. The effects of sex, aging, smoking, drinking alcohol, liver function, and various drugs on ALDH activity were also analyzed. Of the 39 subjects, eight were heterozygotes of the wild (ALDH2*1) and mutant (ALDH2*2) alleles, and the others were homozygotes of the wild allele. ALDH activity toward acetaldehyde in liver mitochondria from subjects with a mutant allele was less than 10% of that with two alleles of wild-type, and the activities toward formaldehyde, propionaldehyde, n-butyraldehyde, capronaldehyde, and heptaldehyde were also significantly lower in the ALDH2*1/*2 rather than ALDH2*1/*1 group. However, the metabolism of octylaldehyde, decylaldehyde, retinaldehyde, benzaldehyde, 3-hydroxybenzaldehyde, and 2,5-dihydroxybenzaldehyde was similar in the two genotypes. Changes in activity in the cytosolic fraction were similar to those in mitochondria. There was no significant difference in ALDH activity in microsomes between the two groups. Total activities of ALDH toward acetaldehyde and other shortchain aliphatic aldehydes in supernatant fractions of homogenized liver were affected in a manner similar to that in mitochondria. Our results suggest that the single nucleotide polymorphisms of the ALDH2 gene only alter the metabolism of aldehydes with a short aliphatic chain. Furthermore, sex, drinking alcohol, and smoking had little effect on ALDH activity, although the activity in elderly individuals tended to be lower albeit statistically insignificant.

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Section: Aldh2 Gene Snps and The Metabolism Of Aldehydessupporting

confidence: 93%

Effects of Aldehyde Dehydrogenase-2 Genetic Polymorphisms on Metabolism of Structurally Different Aldehydes in Human Liver

Wang¹,

Nakajima²,

Kawamoto³

et al. 2002

Drug Metab Dispos

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“…Thus, the decreased activity of gastric Class III (-) ADH in women is consistent with the concentration effect of imbibed alcohol and can explain the lack of gender effects on alcohol bioavailability in studies performed with low concentrations of imbibed alcohol (Ammon et al, 1996;Oneta et al, 1998). In Chinese subjects, a lack of gender effects on ADH activity was reported by Yin et al (1997) and Lai et al (2000) with 500 mM ethanol. This could be due to the less than 25% prevalence of -ADH expression, because the activity of this isozyme (called -ADH by this group) is a major contributor to ethanol oxidation at 500 mM.…”

Section: Discussionsupporting

confidence: 62%

“…Although ADH activity measured at 16 mM ethanol was not significantly affected by age and sex, both factors affected ADH activity measured at 580 mM (Seitz et al, 1993), a concentration like that occurring in the stomach after drinking alcohol (Halsted et al, 1973). In Asian subjects who frequently have a low activity of gastric -ADH isozyme Dohmen et al, 1996;Yin et al, 1993), Harada and Okubo (1993) found less -ADH in Japanese women than in men, whereas no gender differences were detected in Chinese (Lai et al 2000;Yin et al, 1997).…”

mentioning

confidence: 79%

Gender Differences in Pharmacokinetics of Alcohol

Baraona

Abittan

Dohmen

et al. 2001

Alcoholism Clin & Exp Res

465

243

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The gender difference in alcohol levels is due mainly to a smaller gastric metabolism in females (because of a significantly lesser activity of chi-ADH), rather than to differences in gastric emptying or in hepatic oxidation of ethanol. The concentration-dependency of these effects may explain earlier discrepancies. The combined pharmacokinetic differences may increase the vulnerability of women to the effects of ethanol.

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“…Some authors negate these differences [11,13,[24][25][26][27][28][29]; however, the majority of the studies report a significantly higher elimination rate in women [4][5][6][7][8][9][10][11][12][13][14][15][16][17]23,30]. Admittedly, the possible causes discussed in the respective gender-related differences are quite varied.…”

Section: Discussionmentioning

confidence: 99%