Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.1.1.1 (alcohol dehydrogenase)
9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mutagenic activity of diethanolnitrosamine (NDELA), a carcinogenic compound which leads to inconsistent results in standard in vitro procedures was tested in vitro and in animal-mediated assays with the indicator strain Escherichia coli (E. coli) K-12 343/113. This strain allows the simultaneous detection of forward and back mutations arising in several genes of the E. coli chromosome. In animal-mediated assays in which mice were used as hosts for i.v. injected E. coli indicator cells, s.c. application of NDELA induced a dose dependent increase of galactose fermenting mutants in cells recovered from the livers of animals exposed for 3 h to the mutagen. Comparison with results obtained with diethylnitrosamine (DENA) in the same test system revealed that the two compounds apparently cause different types of mutagenic lesions. Induction of arg+ mutations by DENA and several other aliphatic nitrosamines is mainly due to base pair substitutions, whereas NDELA is rather mutagenic in the galRs system. This latter system is, in addition, sensitive to frameshifts and deletions. These differences in mutagenic specificity suggest that NDELA and DENA, although structurally closely related, are activated via different molecular mechanisms. In fact, evidence is accumulating that alcohol dehydrogenase (ADH) could be involved in the activation of NDELA. On the other hand, the effective mutagenesis of NDELA obtained in vitro with E. coli upon addition of rat liver microsomal fraction would not be expected if ADH is involved in the activation since the S-9 Mix used in the present experiments was devoid of cofactors (NAD, NADP), necessary to accomplish oxidation by ADH. Therefore, further in vivo studies were performed, in which pyrazole, a potent blocker of ADH, was administered prior (1 and 24 h) to the injection of the mutagen. The observation that a dose dependent increase of mutants in the liver (and to a lower extent in the spleens) of treated animals takes place under conditions in which ADH activity is blocked, whereas several microsomal enzymes are stimulated, indicated that besides oxidation of NDELA by ADH other metabolic activation pathways are involved. Apparently enzymes contained in the liver homogenate, possibly NADPH dependent enzymes of the microsomal ethanol oxidizing system, play an important role in the formation of mutagenic metabolites of NDELA.
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PMID:Studies on the metabolic activation of diethanolnitrosamine in animal-mediated and in vitro assays using Escherichia coli K-12 343/113 as an indicator. 353 44

Hyponatraemia implies water retention in excess of sodium with or without increased loss of sodium from the body; extracellular fluid volume may be increased, normal or reduced. It has many causes which are briefly reviewed. Among these is the rare syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is suggested that SIADH is often diagnosed incorrectly because the raised ADH levels are appropriate for the volume status of the child. Precision in the diagnosis is important because whilst water restriction is necessary for the treatment of SIADH, other measures including the administration of extra fluid are often required if the raised ADH is appropriate. Hyponatraemia in the newborn may be caused by prerenal failure, renal failure or renal sodium wasting which is common in premature infants. Careful control of sodium intake as well as water intake is vital in this age group. Surgery is associated with water retention, but recent studies suggest that ADH levels are raised post-operatively because of volume depletion and that present recommendations for fluid therapy during and following surgery are inadequate. The use of electrolyte-free dextrose solutions should be abandoned and more liberal use of physiological saline or colloid is recommended.
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PMID:Hyponatraemia in premature babies and following surgery in older children. 360 58

A single-gene nuclear mutant has been isolated in Saccharomyces cerevisiae which cannot grow on minimal medium supplemented with ethanol, acetate, pyruvate, aspartate, or oxaloacetate as sole carbon sources. It will grow on complete medium with these carbon sources, and on minimal medium with dextrose as carbon source. The only supplement which will permit growth on minimal medium with ethanol or pyruvate is aspartate, so the mutant is an aspartate auxotroph when grown on these nonfermentable substrates. It exhibits enhanced levels of phosphoenolpyruvate carboxykinase (EC 4.1.1.49) when grown on dextrose. The mutant can survive as an alcohol dehydrogenase-negative, indicating that the defect is not in the Krebs Cycle or in electron transport. When grown on pyruvate, it produces two to three times as much free alanine and half as much aspartate plus asparagine as the wild type. Two different assays show that the mutant phenotype is due to a deficiency of pyruvate carboxylase (EC 6.4.1.1), an important anaplerotic enzyme. Inferences that can be drawn from the characteristics of this mutant include (a) the glyoxylate cycle is probably located entirely outside the mitochondria, (b) the inner mitochondrial membrane appears to be impermeable to oxaloacetate, and (c) a succinate-malate exchange across the inner mitochondrial membrane connects the glyoxylate and Krebs cycles when yeast is grown on minimal medium with ethanol as a sole carbon source.
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PMID:Pyruvate carboxylase deficiency in yeast: a mutant affecting the interaction between the glyoxylate and Krebs cycles. 388 52

The effect of i.v. Pitressin (ADH) in a dose of 1 U/hr on permeability characteristics and on absorptive capacity of the normal human small intestine was investigated. The method of continuous intestinal perfusion was employed with polyethylene glycol 4000 as a nonabsorbable marker. Unidirectional flux rates of Na and H(2)O were calculated from the disappearance of (22)Na and of (3)HOH from isotonic saline solution within the intestinal lumen. Each study consisted of two successive perfusion periods: one while the subject was hydrated, the other during ADH infusion or while the subject was dehydrated. Water and sodium absorption from isotonic NaCl occurred in the hydrated state and was abolished by ADH as well as by dehydration in the jejunum. In some instances, net gain of water and sodium in the lumen occurred. In the ileum, ADH and dehydration caused a decrease in water and sodium absorption rate. By contrast, unidirectional flux into the intestinal lumen of water and sodium, as well as dextrose and D-xylose diffusion, remained unchanged by ADH. During perfusions with hypertonic urea solutions the rates of sodium and water entry into the intestine were greatly increased during i.v. ADH infusion, whereas urea loss from the study segment remained constant. ADH in the dosage used did not affect human intestinal motility. The results suggest that circulating ADH in physiologic concentrations affects the small intestine in one of two ways: increased secretion of water and salt into the lumen or direct interference with the active sodium transport mechanism.
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PMID:Effect of antidiuretic hormone on human small intestinal water and solute transport. 564 53

1. Gluconeogenesis from 10mm-lactate in the perfused liver of starved rats is inhibited by ethanol. The degree of inhibition reached a maximum of 66% at 10mm-ethanol under the test conditions and decreased at higher ethanol concentrations. The concentration-dependence of the inhibition is paralleled by the concentration-dependence of the activity of alcohol dehydrogenase. The enzyme is also inhibited by ethanol concentrations above 10mm. 2. Gluconeogenesis from pyruvate is not inhibited by ethanol. 3. The degree of the inhibition of gluconeogenesis from lactate by ethanol depends on the concentration of lactate and other oxidizable substances, e.g. oleate, in the perfusion medium. 4. Ethanol also inhibits, to different degrees, gluconeogenesis from glycerol, dihydroxyacetone, proline, serine, alanine, fructose and galactose. 5. The inhibition of gluconeogenesis from lactate by ethanol is reversed by acetaldehyde. 6. Pyrazole, a specific inhibitor of alcohol dehydrogenase, also reverses the inhibition of gluconeogenesis by ethanol. 7. Gluconeogenesis in kidney cortex, where the activity of alcohol dehydrogenase is very low, is not inhibited by ethanol. 8. Kidney cortex, testis, ovary, uterus and certain tissues of the alimentary tract were the only rat tissues, apart from the liver, that showed measurable alcohol dehydrogenase activity. 9. The concentrations of pyruvate in the liver were decreased to about one-fifth by ethanol. 10. The concentration of lactate in the perfused liver was about 3mm below that of the perfusion medium 30min. after the addition of 10mm-lactate. 11. The great majority of the findings support the view that the inhibition of gluconeogensis by ethanol is caused by the alcohol dehydrogenase reaction, which decreases the [free NAD(+)]/[free NADH] ratio. The decrease lowers the concentration of pyruvate and this is the immediate cause of the inhibition of gluconeogenesis from lactate, alanine and serine: the fall in the concentration of pyruvate lowers the rate of the pyruvate carboxylase reaction, one of the rate-limiting reactions of gluconeogenesis. The cause of the inhibition of gluconeogenesis from other substrates is discussed.
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PMID:Inhibition of hepatic gluconeogenesis by ethanol. 577 87

D-Fructose and D-glucose activate alcohol dehydrogenase from horse liver to oxidize ethanol. One mol of D-[U-14C]fructose or D-[U-14C]glucose is covalently incorporated per mol of the maximally activated enzyme. Amino acid and N-terminal analyses of the 14C-labelled glycopeptide isolated from a proteolytic digest of the [14C]glycosylated enzyme implicate lysine-315 as the site of the glycosylation. 13C-n.m.r.-spectroscopic studies indicate that D-[13C]glucose is covalently linked in N-glucosidic and Amadori-rearranged structures in the [13C]glucosylated alcohol dehydrogenase. Experimental results are consistent with the formation of the N-glycosylic linkage between glycose and lysine-315 of liver alcohol dehydrogenase in the initial step that results in an enhanced catalytic efficiency to oxidize ethanol.
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PMID:Activation of liver alcohol dehydrogenase by glycosylation. 634 12

Rat hepatocytes were isolated by a collagenase perfusion technique with subsequent subfractionation on Metrizamide gradients into subpopulations which have been designated band I and band II and are likely to be enriched with centrilobular and periportal cells, respectively. Band I was found to have a higher concentration of 5'-nucleotidase and band II a higher concentration of alcohol dehydrogenase. Furthermore, pretreatment of rats with phenobarbital led to higher cytochrome P-450 in the band I (centrilobular enriched) as compared to the band II (periportal enriched) subpopulations of hepatocytes. These data support their ascribed lobular origins. The uptake of a single concentration of galactose, ouabain and taurocholate into each of the two subpopulations was investigated until the concentration within the hepatocytes no longer increased. No difference was found in the uptake of [14C]galactose (25 mM) between the two hepatocyte subpopulations. However, the uptake of [3H]ouabain (125 microM) was greater in the centrilobular as compared to periportal enriched fraction of the hepatocytes. An even greater difference was found for the uptake of [3H]taurocholate (25 microM). The kinetics of taurocholate uptake were subsequently investigated. The Km for each subpopulation was 21 microM, while the Vmax of the centrilobular enriched fraction was 2.03 and that of the periportal enriched fraction was 1.57 nmol/min/mg of protein. These results show that there is a difference in uptake into hepatocytes of centrilobular and periportal origin for ouabain and taurocholate, but not for galactose.
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PMID:Uptake of galactose, ouabain and taurocholate into centrilobular and periportal enriched hepatocyte subpopulations. 720 41

We isolated numerous mutants of Streptomyces fradiae blocked in tylosin biosynthesis after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. These mutants were classified into nine groups, based upon the tylosin-like compounds produced and upon cofermentation analyses. More than 80% of the mutants isolated produced no tylosin-like compounds, and the majority of these were blocked only in the formation of tylactone. Four classes of mutants blocked in the biosynthesis or addition of tylosin sugars were isolated; tylA mutants were blocked in the formation of all three tylosin sugars, whereas tylB, tylC, and tylD mutants were blocked specifically in the biosynthesis or the addition of mycaminose, mycarose, and 6-deoxy-d-allose, respectively. Two classes of mutants (tylH and tylI) blocked in specific oxidations of tylactone and two classes (tylE and tylF) blocked in specific O-methylations of demethylmacrocin and macrocin were also characterized. Cofermentation and bioconversion studies with these mutants suggested the following relationships: (i) the tylosin sugars are derived from a common intermediate; (ii) tylactone is the first intermediate which can be excreted in appreciable quantities; (iii) the addition of mycaminose to the C-5 hydroxyl group of tylactone must precede oxidations at C-20 and C-23; (iv) oxidation at C-20 normally precedes the attachment of mycarose to the 4' hydroxyl position of mycaminose; and (v) 6-deoxy-d-allose is added to the C-23 hydroxyl position of the lactone and subsequently O-methylated at 2''' and 3''' positions. The O-methylations appear to be the final two steps in tylosin biosynthesis, and the 2''' O-methylation must occur before the 3''' O-methylation can take place. All of the tyl mutants except the tylG mutants produced relatively high levels of tylosin-like intermediates or shunt products. Mutants blocked in specific steps other than 3''' O-methylation, including a mutant blocked in 2''' O-methylation of demethylmacrocin, produced normal levels of macrocin O-methyltransferase. Mutants apparently containing specific tylosin structural gene mutations produced normal levels of aerial mycelia and spores, produced low levels of tylosin aldehyde reductase, and were resistant to high levels of tylosin. However, three atypical tylG mutants produced no tylosin-like compounds, could not cosynthesize tylosin with any other tyl mutant, could not bioconvert tylactone or macrocin to tylosin, and produced no macrocin O-methyltransferase. These three mutants produced elevated levels of tylosin aldehyde reductase. In addition, one was very succeptible to tylosin and did not produce aerial mycelia or spores.
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PMID:Properties of Streptomyces fradiae mutants blocked in biosynthesis of the macrolide antibiotic tylosin. 728 18

Two mutants carrying different deletions of the IMP2 coding sequence of Saccharomyces cerevisiae, delta T1, which encodes a protein lacking the last 26 C-terminal amino acids, and delta T2, which completely lacks the coding region, were analysed for derepression of glucose-repressible maltose, galactose, raffinose and ethanol utilization pathways in response to glucose limitation. The role of the IMP2 gene product in the regulation of carbon catabolite repressible enzymes maltase, invertase, alcohol dehydrogenase, NAD-dependent glutamate dehydrogenase (NAD-GDH) and L-lactate:ferricytochrome-c oxidoreductase (L-LCR) was also analysed. The IMP2 gene product is required for the rapid glucose derepression of all above-mentioned carbon source utilization pathways and of all the enzymes except for L-LCR. NAD-GDH is regulated by IMP2 in the opposite way and, in fact, this enzyme was released at higher levels in both imp2 mutants than in the wild-type strain. Therefore, the product of IMP2 appears to be involved in positive and negative regulation. Both deletions result in growth and catalytic defects; in some cases partial modification of the gene product yielded more dramatic effects than its complete absence. Moreover, evidence is provided that the IMP2 gene product regulates galactose- and maltose-inducible genes at the transcriptional level and is a positive regulator of maltase, maltose permease and galactose permease gene expression.
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PMID:IMP2, a gene involved in the expression of glucose-repressible genes in Saccharomyces cerevisiae. 749 32

Glucose-repressed growth of Saccharomyces cerevisiae was analysed in a nitrogen-limited continuous culture at different dilution rates (D). The glucose consumption of the yeast decreased from 3.4 g g-1 h-1 to 3.0 g g-1 h-1 when D was decreased from 0.3 h-1 to 0.15 h-1. No transcripts of the SUC2 and HXK1 genes, encoding, respectively, invertase and hexokinase isoenzyme 1, could be detected. Because both genes are regulated by glucose repression at the transcriptional level, this confirmed that the culture was glucose repressed at every D. During the decrease in D, no change in the activities or mRNA levels of key enzymes in carbon metabolism was observed, except for alcohol dehydrogenases I and II and phosphoglucomutase. These enzymes increased in activity and/or mRNA level when D was decreased, which was also observed in glucose- and galactose-limited continuous cultures. This demonstrates that the expression levels of alcohol dehydrogenases I and II, and also phosphoglucomutase, are coupled to the growth rate of the organism. A comparison between the alcohol dehydrogenase II activity in glucose- and nitrogen-limited continuous cultures demonstrated that the growth rate contributes as much to repression of alcohol dehydrogenase II activity as does glucose. Both the glucose consumption and the activity of the glycolytic enzymes were relatively constant when D was decreased and, as a consequence, the concentrations of intracellular metabolites remained constant. A slight decrease in the glucose 6-phosphate concentration was observed, which could be caused by the slight decrease in glucose consumption at low D values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A nitrogen-limited, glucose-repressed, continuous culture of Saccharomyces cerevisiae. 801 81


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