Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. This study investigates the acetylation of 5-aminosalicylic acid by isolated human colonic epithelial cells. 2. After incubation of intact cells with 0.1 mmol/l 5-aminosalicylic acid, N-acetyl-5-aminosalicylic acid was detected in a concentration of 141 (+/- 23.8 SEM) nmol/g dry weight in the incubation medium, and 34.8 (+/- 5.5 SEM) nmol/g dry weight intracellularly. No unchanged 5-aminosalicylic acid was detected inside the cell. 3. Acetylation of 5-aminosalicylic acid by a cell homogenate was very poor, but the addition of 1 mmol/l acetyl-CoA resulted in complete conversion of 0.1 mmol/l 5-aminosalicylic acid to N-acetyl-5-aminosalicylic acid. 4. N-Acetyltransferase activity was detected in the cytosol, with a mean of 3.3 nmol min-1 mg-1 of protein. There was no N-acetyltransferase activity in the brush border. There was no difference in enzyme activity between epithelial cells derived from normal, Crohn's disease or ulcerative colitis patients. 5. Preliminary characterization of the N-acetyltransferase enzyme suggests a molecular weight of 150,000.
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PMID:Acetylation of 5-aminosalicylic acid by isolated human colonic epithelial cells. 215 87

The chick pineal gland expresses a circadian rhythm of melatonin biosynthesis, with elevated levels at night and low levels during the day. The rhythm of melatonin is regulated both by circadian oscillators located within the gland itself and by adrenergic input from the sympathetic nervous system. Previous work has shown that norepinephrine administration inhibits melatonin biosynthesis, as measured by the activity of the enzyme serotonin N-acetyltransferase. As a first step toward understanding the mechanisms by which norepinephrine regulates melatonin production in the chick pineal, we have identified the adrenergic receptor involved. Dissociated chick pineal cell cultures were prepared and melatonin release was measured on days 5 and 6 of culture using radioimmunoassay. The effects of adrenergic agonists and antagonists on the nocturnal increase of melatonin release during the 12 hr dark portion of a LD12:12 light cycle were determined. Norepinephrine inhibited melatonin release in a dose-dependent manner, with an average EC50 of 19.7 nM +/- 2.23 (SEM). Melatonin release values ranged from 100 to 4% of the level seen in control cultures, depending on the dose of norepinephrine. The physiological response to epinephrine, norepinephrine, and isoproterenol was stereospecific. The (-) stereoisomer was 6, 8, and 37 times more potent than the (+) stereoisomer, respectively. EC50 values (in nM) for adrenergic agonists were as follows: alpha-methyl-(-)-norepinephrine, 2.46; tramazoline, 3.06; guanabenz, 3.31; clonidine, 3.70; oxymetazoline, 4.29; (-)-epinephrine, 7.44; (-)-norepinephrine, 19.7; (-)-isoproterenol, 463; and (-)-phenylephrine, 659. Schild analysis was used to determine the relative potency of adrenergic antagonists. pA2 values for adrenergic antagonists were as follows: rauwolscine, 9.55; RX78 1094, 8.32; yohimbine, 8.14; phentolamine, 7.11; prazosin, 5.93; and (-)-propranolol, less than 6. The relative potencies of both adrenergic agonists and antagonists demonstrate that alpha-2 receptors mediate norepinephrine-induced inhibition of melatonin release in chick pineal cell cultures. The identification of alpha-2 receptors in chick pineal cells should aid in our understanding of the biochemical events initiated by receptor activation that regulate melatonin synthesis.
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PMID:Alpha-2 adrenergic regulation of melatonin release in chick pineal cell cultures. 289 Jul 22

The authors examined the activity of N-acetyltransferase and that of microsomal P-450 isoenzymes in health and hepatic disease state by determining the acetylation phenotype and the total (CLAP) and metabolic clearances of antipyrine to form norantipyrine or N-demethylantipyrine (MCLnora), 3-hydroxymethylantipyrine (MCLhma), and 4-hydroxyantipyrine (MCLha) in 21 healthy subjects and in 33 patients with chronic liver diseases (CLD) and investigated the relationship between the activities of these two enzyme systems. The acetylation phenotype was determined according to the urinary caffeine metabolites test. The mean and (SEM) of CLAP, MCLhma, MCLha, and MCLnora in healthy subjects were 2.42 (0.264), 0.193 (0.031), 0.322 (0.045), and 0.288 (0.04) L/h, and those observed in patients with CLD were 0.98 (0.1), 0.076 (0.015), 0.131 (0.026), 0.103 (0.022) L/h, respectively. The prevalence of fast acetylation among the healthy subjects and patients with CLD was 38% and 39%, respectively. Although all metabolic clearances appear to be reduced in healthy slow acetylators, the reduction was only significant in MCLnora, indicating a direct association between the activity of N-acetyltransferase and that of P-450 IIIA3 responsible for the N-demethylation of antipyrine. Conversely, slow acetylators with CLD exhibited significantly higher CLAP and near-significantly larger metabolic clearances including MCLnora, which suggests that P-450 activity in fast acetylators is more sensitive to chronic liver diseases than in slow acetylators.
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PMID:Relationship between antipyrine metabolism and acetylation phenotype in health and chronic liver diseases. 766 22

Placental biotransformation reactions may modulate the effect a xenobiotic has on the developing fetus. However, in spite of the critical role the placenta plays in supporting fetal life, little is known about the pharmacology and toxicology of the human placenta. Our laboratory has previously characterized the N-acetylation activity of the human term placenta. This activity is predominantly attributable to the NAT1 form of arylamine N-acetyltransferase (NAT). Although acetylation is generally thought to be a detoxifying reaction, both N-acetylation and deacetylation reactions play an important role in the activation of carcinogenic arylamines to their reactive and toxic forms. In the current study we characterized the activity of human placental NAT and deacetylase toward the carcinogenic arylamine, 2-aminofluorene (AF) and its acetylated metabolite, 2-acetylaminofluorene (AAF). 2-Aminofluorene is a synthetic, prototype carcinogenic arylamine compound, and its metabolism has been extensively studied in the laboratory. Our data show that the affinity (Km = 24.2 +/- 1.66 mumol/L; mean +/- SEM, n = 6) and maximal velocity (Vmax = 4.29 +/- 0.33 nmol/min/mg; mean +/- SEM, n = 6) of AF N-acetylation by human placenta are similar to those in human liver. The deacetylation of AAF to AF by placental microsomes may be catalyzed by a carboxylesterase. However, our studies with inhibitors reveal that the characteristics of human placental deacetylation activity differ from that of human liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biotransformation of carcinogenic arylamines and arylamides by human placenta. 803 95

1. An arylalkylamine N-acetyltransferase (NAT) of the parasitic nematode, Ascaridia galli was studied using either [14C]serotonin (5-HT) or [14C]octopamine (OA) as substrates and with acetyl-CoA as the donor of the acetate group. 2. The NAT activity towards 5-HT and OA co-eluted from a size-exclusion column and appeared to have an M(r) of around 30,000. The enzyme had apparent Km values of 540 +/- 100 microM (+/- SEM) and 33 +/- 4 microM (+/- SEM) for 5-HT and octopamine, respectively, when assayed in the presence of 1 mM acetyl-CoA. 3. High levels of NAT were found in the gonads of male and female worms and the muscle/body wall. 4. N-acetylation was strongly inhibited by Cu2+ but not by other divalent metal ions and the effect of a number of compounds including biogenic amines, formamidines, hydrazines, and beta-carbolines on the arylalkylamine N-acetyltransferase activity was studied.
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PMID:Properties of an arylalkylamine N-acetyltransferase from the nematode, Ascaridia galli. 829 55

It has been postulated that Mg depletion is associated with decreased melatonin. Exogenous magnesium (Mg) has been found to increase the activity of serotonin N-acetyltransferase, an enzyme in the pathway for melatonin synthesis; but no data have been found on the effect of Mg deficiency on plasma melatonin. This pilot study examined the effect of a dietary Mg deficiency on plasma melatonin in male, Sprague-Dawley rats. Weanling rats were placed on a Mg-deficient (150 ppm) or a Mg-adequate (1000 ppm) diets for four weeks, after which they were sacrificed 4, 5 or 7 hours into the dark cycle. Plasma was assayed for melatonin concentrations. A significant decrease (p = 0.0101) occurred in mean (+/- SEM) plasma melatonin levels of the Mg-deficient animals (50 +/- 6.4 pg/mL) when compared to the Mg-adequate animals (75 +/- 6.6 pg/mL). There was no obvious phase shift in the melatonin profile of the Mg-deficient animals when compared to the Mg-adequate animals.
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PMID:Dietary magnesium deficiency decreases plasma melatonin in rats. 1717 5