Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several alterations of the small-intestinal morphology and function have been documented after alcohol ingestion. There are morphologic changes macroscopically and microscopically after acute alcohol administration in the proximal part of the small intestine, which are quickly reversible. There are no macroscopic changes and, in most patients, very discrete light microscopic changes in the small intestine after chronic alcohol ingestion. The ultrastructural changes are, however, profound, as seen by both transmission and scanning electron microscopy. The permeability is probably increased, permitting entrance of possible noxious agents, which may explain some of the extraintestinal tissue damage observed in chronic alcoholism. The transit is increased, at least after acute alcohol administration, perhaps contributing to the diarrhea commonly seen after heavy drinking. Several of the enzymes located in the brush border are affected; lactase activity can be depressed and perhaps result in a transient milk intolerance in predisposed individuals. The activity of GGT is increased and may partly account for the GGT elevation in serum after heavy drinking. Other enzymes, such as Na(+)-K(+)-ATPase, can be inhibited and result in a decreased absorption of substances that require active, energy-dependent transport mechanisms. The secretion of water and electrolytes may be increased (an effect on cAMP?). The absorption of several nutrients, vitamins, and other elements is disturbed. The bacterial flora is increased and changed, which may give rise to symptoms and also increase the production of acetaldehyde by bacterial metabolism of ethanol. Acetaldehyde is more toxic than ethanol, and an increased concentration of acetaldehyde can possibly accentuate the damage to the liver and other organs. The bacterial overgrowth can possibly cause endotoxinemia. Although studies on alcohol-related intestinal alterations have been relatively sparse, the acute and chronic effects of alcohol thus seem to be considerable. From available results it is, however, difficult to draw any definite conclusions about the clinical importance of many of the findings. Future research will need to study the relationship between, for example, the chronic morphologic changes, the absorptive dysfunction, and permeability alterations, on the one hand, and the gastrointestinal symptoms, the extraintestinal damage, and various deficiencies, on the other hand.
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PMID:Alcohol and the small intestine. 200 95

The treatment of Caco-2 cells, a human colon adenocarcinoma cell line that closely resembles normal human small intestinal epithelial cells, with acetaldehyde resulted in significantly decreased activities of brush border enzymes sucrase, maltase, lactase, and gamma-glutamyltransferase; alkaline phosphatase activity was not affected. In the case of sucrase and maltase, the activities were also decreased by a combination of acetaldehyde and ethanol, although ethanol alone markedly increased them. The possibility that intraintestinal acetaldehyde, formed by intestinal microbes, might play a role in some small intestinal enzyme deficiencies observed earlier in alcoholics should therefore be considered. The mechanism by which acetaldehyde alters these enzyme activities remains unclear. The observation that acetaldehyde also disturbed cell polarization, an initial step in the process of differentiation in Caco-2 cells, indicates that acetaldehyde might decrease these enzyme activities by interfering with cell differentiation. Because ethanol and acetaldehyde metabolizing enzymes have not been previously studied from Caco-2 cells, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were also measured from these cells, and their ALDH isoenzyme pattern was characterized. Like many cancerous cell lines, Caco-2 cells were found to express no ADH. They, however, possessed ALDH activity that was comparable with normal colonic mucosal activity and also expressed the same ALDH classes (ALDHs 1 to 3) than normal human colonic mucosa.
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PMID:Effects of acetaldehyde on brush border enzyme activities in human colon adenocarcinoma cell line Caco-2. 943 18

Human settlement from the African ancestral home was accompanied by cultural and genetic adaptation to new habitat conditions (climate, infections, diet, etc.). We previously suggested for the first time an approach to the identification of human genes presumably involved in adaptation to evolutionary new environmental factors based on a combination of genetic and humanitarian methods of study. In order to search for the genes involved in adaptation and for environmental factors (to which this adaptation occurs), we attempted to find correlations between the population allele frequencies of the studied gene and formalized descriptions of peculiarities of the habitat of ethnic groups given in "Ethnographic Atlas" by G. P. Murdock. In the presented review, we summarized our own data on an experimental determination of the allele frequencies for lactase (LCT*), apolipoprotein E (APOE), and alcohol dehydrogenase (ADH1B) genes in populations of Russia. Based on these data and available materials of other investigators, we developed maps of worldwide allele frequency distribution for these genes. We detected a correlation of allele frequencies of these genes in populations with the presence of certain factors of the environment that these populations inhabit. It was also confirmed that the evolutionarily young LCT*-13910T allele, which determines lactase persistence and the possibility of milk consumption in adults, is distributed in populations for which dairy animal husbandry is typical. During the analysis of 68 populations, we for the first time demonstrated that the frequency of the APOE e4 allele (which is ancestral for humans and influences the lipid metabolism) is higher in groups with a high contribution of hunting and gathering. Our data are in favor of the hypothesis that it was exactly the e4 allele that was a subject for selection, while the e3 allele was less important for adaptation. We also for the first time demonstrated that the evolutionarily young ADH1B*48His allele (which determines a high rate of ethanol metabolism into acetaldehyde) is presented with a large frequency in those populations where filariasis is endemic. The obtained data indicate the possible involvement of endogenous ADH1B gene substrates or their metabolites in the resistance to filaria and open a new path to the development of drugs for this widespread human disease.
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PMID:[Combination of Genetic and Humanitarian (Cross-Cultural) Methods for the Identification of Human Genes Involved in the Process of Adaptation to Evolutionary New Environmental Factors]. 2608 23