Koivisto T, Salaspuro M
Research Unit of Alcohol Diseases, University of Helsinki, Finland.
Alcohol Clin Exp Res. 1996 May;20(3):551-5. doi: 10.1111/j.1530-0277.1996.tb01091.x.
Intracolonic bacteria have previously been shown to produce substantial amounts of acetaldehyde during ethanol oxidation, and it has been suggested that this acetaldehyde might be associated with alcohol-related colonic disorders, as well as other alcohol-induced organ injuries. The capacity of colonic mucosa to remove this bacterial acetaldehyde by aldehyde dehydrogenase (ALDH) is, however, poorly known. We therefore measured ALDH activities and determined ALDH isoenzyme profiles from different subcellular fractions of rat colonic mucosa. For comparison, hepatic, gastric, and small intestinal samples were studied similarly. Alcohol dehydrogenase (ADH) activities were also measured from all of these tissues. Rat colonic mucosa was found to possess detectable amounts of ALDH activity with both micromolar and millimolar acetaldehyde concentrations and in all subcellular fractions. The ALDH activities of colonic mucosa were, however, generally low when compared with the liver and stomach, and they also tended to be lower than in small intestine. Mitochondrial low K(m) ALDH2 and cytosolic ALDH with low K(m) for acetaldehyde were expressed in the colonic mucosa, whereas some cytosolic high K(m) isoenzymes found in the small intestine and stomach were not detectable in colonic samples. Cytosolic ADH activity corresponded well to ALDH activity in different tissues: in colonic mucosa, it was approximately 6 times lower than in the liver and about one-half of gastric ADH activity. ALDH activity of the colonic mucosa should, thus, be sufficient for the removal of acetaldehyde produced by colonic mucosal ADH during ethanol oxidation. It may, however, be insufficient for the removal of the acetaldehyde produced by intracolonic bacteria. This may lead to the accumulation of acetaldehyde in the colon and colonic mucosa after ingestion of ethanol that might, at least after chronic heavy alcohol consumption, contribute to the development of alcohol-related colonic morbidity, diarrhea, and cancer.
先前的研究表明,结肠内细菌在乙醇氧化过程中会产生大量乙醛,有人认为这种乙醛可能与酒精相关的结肠疾病以及其他酒精引起的器官损伤有关。然而,结肠黏膜通过醛脱氢酶(ALDH)清除这种细菌产生的乙醛的能力却鲜为人知。因此,我们测定了大鼠结肠黏膜不同亚细胞组分的ALDH活性,并确定了ALDH同工酶谱。为了进行比较,我们对肝脏、胃和小肠样本也进行了类似的研究。我们还测定了所有这些组织的乙醇脱氢酶(ADH)活性。结果发现,大鼠结肠黏膜在微摩尔和毫摩尔乙醛浓度下以及所有亚细胞组分中都具有可检测到的ALDH活性。然而,与肝脏和胃相比,结肠黏膜的ALDH活性通常较低,而且也往往低于小肠。结肠黏膜中表达了线粒体低Km值的ALDH2和对乙醛具有低Km值的胞质ALDH,而在小肠和胃中发现的一些胞质高Km值同工酶在结肠样本中无法检测到。不同组织中胞质ADH活性与ALDH活性高度对应:在结肠黏膜中,它比肝脏中约低6倍,约为胃ADH活性的一半。因此,结肠黏膜的ALDH活性应该足以清除乙醇氧化过程中结肠黏膜ADH产生的乙醛。然而,它可能不足以清除结肠内细菌产生的乙醛。这可能导致摄入乙醇后结肠和结肠黏膜中乙醛的积累,这至少在长期大量饮酒后,可能会导致酒精相关的结肠疾病、腹泻和癌症的发生。