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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiulcerogenic drug ranitidine, given orally to mice, brought about reductions of kidney-bound hydrolytic enzymes at three different dose levels, viz. 10 mg, 100 mg, and 1000 mg/kg body weight, and for three different time points (single administration for 2 h and 24 h, and daily administration for 15 days). The activities of Na+, K(+)-ATPase, Ca2(+)-ATPase, and Mg2(+)-ATPase (marker enzymes of basolateral membranes) were reduced, and these reductions were significant at higher doses and after a 24-h single treatment or 15 days' daily treatment. Maltase, alkaline phosphatase, and leucine aminopeptidase (marker enzymes of brush border membrane [BBM]) activities were significantly inhibited after ranitidine treatment. Kinetic analysis of BBM-associated enzymes indicated that ranitidine decreased the maximum of apparent initial enzyme velocity (Vmax) of maltase, alkaline phosphatase, and leucine aminopeptidase. The substrate affinity constant (Km) was decreased in the case of alkaline phosphatase and maltase, while it was not altered in the case of leucine aminopeptidase. In vitro addition of ranitidine to renal BBM also produced significant inhibition of these enzymes, the inhibition constants (Ki) for maltase, alkaline phosphatase, and leucine aminopeptidase being 7.5, 15.5, and 3.5 mM, respectively. Membrane-bound lipid estimation showed a significant increase in phospholipids, triglycerides, and free fatty acids. Cholesterol, however, was decreased in both renal basolateral and brush border membranes.
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PMID:Effect of histamine H2-receptor antagonist, ranitidine on renal brush border and basolateral membranes. 217 15

The dose relationship between medroxyprogesterone acetate (MPA), a long acting contraceptive, and rat intestinal digestive and absorptive functions has been investigated. The study revealed that the activities of brush border sucrase, lactase and leucine aminopeptidase were stimulated only at high doses, viz 70 mg/kg (180 mumol/kg) body weight and above, whereas the activity of alkaline phosphate was depressed at comparatively low dose (17.5 mg/kg; 45 mumol/kg body weight). This decrease was found to be significant (p less than 0.001) at all the doses tested. The inhibition in the intestinal uptake of calcium paralleled the decrease in alkaline phosphatase activity. Relatively high amount of MPA (140 mg/kg; 360 mumol/kg) was required to augment the uptake of glucose and amino acid. The results obtained do not indicate a close relationship between the dose of the drug and the extent of alteration in the rat intestinal digestive and absorptive functions. The study appears to confirm the association between brush border enzymes activities and uptake of nutrients in rat intestine.
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PMID:Effect of various doses of medroxyprogesterone acetate on intestinal functions in rats. 230 1

49 women of reproductive age were included in the study and were divided in 2 groups. The ovulation inhibitor group (OI) consisted of 37 women aged 33.5-39 exposed to ovulation inhibitors for an average of 13.4 years (Ovosiston, Sequenzovosiston, Non-Ovlon), and the control group consisted of 12 women aged 35.5-41.5 who had taken no OI for at least 5 years. Aspartate-aminotransferase (serum glutamic oxaloacetic transaminase=SGOT) and alanine aminotransferase (serum glutamic pyruvic transaminase) enzymes were determined as indicators of liver damage, and gamma-glutamyl-transferase (gamma-GT) for indication of cholestasis or as a sensitive parameter of hepatopathy. By using a nonradiating, stabile isotop-marked tracer substance, 15 N-ammonium chloride, the uric acid synthesis performance and the ammonium excretion of the liver could be evaluated. The Q-value indicated an excess of ammonium and uric acid as demonstrated by the 15 N test. Significant differences were found between the 2 groups with regard to ALAT, gamma-GT, Q-value, and leukocyte count. The measured values of enzymes and leukocytes studied, however, stayed within the normal range. In the OI group, the decreased gamma-GT activity was surprising. Also, the Q-value showed a slightly pathological median value in 18 women of the OI group. In 4 women who has Q-values of 1.6 to 1.9 (vs. 1.4 median value), liver punction was performed. In each case, liver damage could be shown to be attributed to use of contraceptives. Morphological changes indicating enhanced detoxification activity, and liver cell fat formation of various severity were also found as uncharacteristic alterations. The described increase of the serum activity of aminotransferase, leucine aminopeptidase, alkaline phosphatase, and gamma-GT were interpreted as the expression of cellular adaptation. Long-term use of hormonal contraceptives influences the metabolism of the liver, whose partial disorder can be detected by the 15 N-ammonium test. Normal ALAT and gamma-GT serum enzyme activity in single cases does not allow conclusions on the behavior of the metabolism of the liver.
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PMID:[Use of the stable nitrogen isotope 15N in assessing liver metabolism in hormonal contraception]. 231 86

The present studies were conducted to determine if diets containing a large amount of fat stimulate the regeneration of damaged intestinal mucosa in the presence or absence of essential fatty acid deficiency. To simulate injury, male Sprague-Dawley rats were given methotrexate, 2.5 mg/kg body wt, subcutaneously for 3 consecutive days. Twenty-four hours after the last methotrexate injection, rats were placed on diets containing either 0%, 1%, or 10% safflower oil. Mucosal weight, protein, deoxyribonucleic acid, maltase, sucrase, lactase, alkaline phosphatase, leucine aminopeptidase, and fatty acids were all determined 3 and 12 days after methotrexate. Crypt-cell production rates were also determined. Essential fatty acid deficiency was confirmed in the 0% safflower oil group, in which triene-tetraene ratios were greater than 0.4. Mucosal weight, deoxyribonucleic acid, protein content, and villus height were all greater in the 1% safflower oil group than in the 0% group at 12 days. In the ileum, 1-h thymidine incorporation was greater in the 0% safflower oil group than in the other two groups. No differences in any of the parameters studied were observed between the 1% and 10% groups. These results suggest that diets deficient in essential fatty acids may impair the recovery of intestinal mucosa from injury.
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PMID:Effects of dietary lipids on recovery from mucosal injury. 232 15

The effect of methylglyoxal on protein -SH and -NH2 groups in cytosolic and membranous fractions of epithelial cells lining the gastrointestinal tract of rat was investigated, using isolated villus and crypt cells (enterocytes) and colonocytes. It was found that 11-12% cytosolic protein -SH and 14-17% membrane protein -SH groups were lost when villus and crypt cells were treated with 2 mM methylglyoxal. In colonocytes, the corresponding loss in protein -SH groups was 46 and 30% under the same treatment. Similarly, 27-37% protein -NH2 group in the cytosolic fraction and 18-19% protein -NH2 group in membranous fractions of the enterocytes were lost by 2 mM methylglyoxal treatment. In colonocytes, the loss of protein -NH2 group was 30 and 15% in cytosolic and membranous fractions, respectively, under the same treatment. Effect of methylglyoxal on activity of various brush border enzymes such as alkaline phosphatase, gamma-glutamyl transpeptidase, leucine aminopeptidase, Mg2(+)-ATPase, sucrase and lactase was also studied. Alkaline phosphatase and gamma-glutamyl transpeptidase activities were inhibited to the extent of 30 and 15% respectively. There was no significant change in the activities of other enzymes after treating the brush border vesicles with 2 mM methylglyoxal. These findings show that methylglyoxal can cause loss of protein thiol and amino groups and enzyme activity in mucosal cells of rat gastrointestinal tract and the effect is more pronounced in colonocytes, which are in constant contact with bacterial metabolites.
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PMID:Effect of methylglyoxal on protein thiol and amino groups in isolated rat enterocytes and colonocytes and activity of various brush border enzymes. 234 Nov 60

Oral administration of cimetidine, an antiulcerogenic drug, at a dose of 100 mg per kg body weight in mice, caused significant inhibition of glucose and amino acid uptake in small intestinal segments either after 2 and 24 h (single treatment) or 15 days (daily). Cimetidine also caused a significant decrease in intestinal brush border membrane associated enzymes, sucrase, lactase, maltase and alkaline phosphatase, but increases the activity of leucine aminopeptidase. Kinetic analysis indicated that cimetidine decreased the maximum of apparent initial enzyme velocity (Vmax) of disaccharidases, while substrate affinity constant (Km) was not altered, indicating the noncompetitive nature of inhibition. However, the inhibition of alkaline phosphatase was found to be of mixed type as both Km and Vmax were altered. In vitro addition of cimetidine also produced significant inhibition of enzymes, the inhibition constant (Ki) for sucrase, lactase, maltase and alkaline phosphatase being 22.8, 4.5, 11.5 and 4.8 mM, respectively. It was further observed that in vitro addition of cimetidine also decreased Vmax in case of maltase, sucrase and lactase, Km was unchanged, whereas in case of alkaline phosphatase there was a decrease in Vmax and increase in Km, as compared to the controls.
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PMID:Effect of cimetidine on intestinal absorption & digestive functions in mice. 237 90

Intestinal and serum leucine aminopeptidase (LAP) and alkaline phosphatase (AKP) were characterized by electrophoresis for eight inbred strains of laboratory mice. Intestinal LAP and AKP of adult mice were expressed concordantly within strains, as banded or diffuse, and concordantly for rate of migration within strains that had diffuse isozymes. All strains, except DD/S, had a single band of serum LAP and a single, diffuse zone of serum AKP. DD/S had a double band of serum LAP as well as isozymes of intestinal LAP and AKP unlike those of other strains. All strains displayed similar, neuraminidase-sensitive isozymes of intestinal LAP and of AKP prior to weaning, but after weaning there was marked sensitivity to neuraminidase only in DD/S. In interstrain crosses, banded/diffuse, migration rate, and neuraminidase sensitivity were inherited as independent autosomal traits, with indications of variable penetrance and genetic interaction.
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PMID:Intestinal leucine aminopeptidase and alkaline phosphatase: genetic regulation and development in mice. 239 81

Several complexes of enzymes and immunoglobulins were detected at the same time in the serum of a patient with seropositive rheumatoid arthritis. The enzymes which were found to complex with immunoglobulins were lactate dehydrogenase, alkaline phosphatase (liver, bone, placental, and intestinal isoenzymes), amylase, cytosol leucine aminopeptidase, and microsomal leucine aminopeptidase. Reconstitution studies after papain or pepsin digestion showed that the association site of the enzymes was in the Fab portion of the immunoglobulin component. We found these complexes to be the result of an antibody-antigen reaction. The binding capacity of each enzyme was variable over the entire time course. The patient's immunoglobulins, complexed with lactate dehydrogenase or amylase, could not be reconstituted using alkaline phosphatase, cytosol leucine aminopeptidase, or microsomal leucine aminopeptidase in vitro. Therefore, this suggests that the immunoglobulins which bind to each enzyme are independent of each other.
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PMID:A case of rheumatoid arthritis with various enzyme-immunoglobulin complexes. 242 42

Primary cultures were obtained from microdissected rabbit proximal tubules (S1 segments). The growing epithelia were maintained in culture for up to 30 days. Electron microscopy study revealed that the cells formed a monolayer and showed a morphological polarity with apical microvilli and tight junctions. An immunofluorescence technique using two monoclonal antibodies raised against two apical brush border enzymes of the proximal tubule (LAP, DPP IV) revealed that these enzymes were expressed in the cultured cells. Membrane associated and cytosolic enzyme activities were measured on 12, 20 and 30-day-old cultures. Cultured epithelia exhibited leucine aminopeptidase, gamma glutamyl transferase and fructose 1-6 biphosphatase activities that remained constant for up to 30 days, whereas alkaline phosphatase activity decreased in the oldest cultures. Hexokinase activity on the other hand, increased after 12 days of culture. Cyclic AMP synthesis was stimulated by parathyroid hormone at 12, 20 and 30 days of culture and was insensitive to arginine vasopressin. After 20 days of culture the epithelia grown on permeable supports developed a transepithelial potential of -0.13 mV (apical negative) and a transepithelial resistance of 37 omega cm2 that increased to -1.13 mV and 60 omega cm2 respectively in 30-day-old cultures. The patch clamp technique was applied to the apical membrane of 12-15-day-old cultures. In the whole cell recording configuration, a cellular potential of -61.5 mV was measured, which was mainly due to K+ diffusion. A non-selective cationic channel was present in the apical membrane of the cultured cells. In cell-attached patches the channel carried an inward current and had a conductance of 13 pS. On excised patches the channel discriminated poorly between Na+ and K+ and was impermeant to Cl- and its conductance ranged between 20 and 28 pS. The channel activity was not voltage dependent but required a high calcium concentration (1 mM Ca2+) on the cytoplasmic face.
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PMID:Patch clamp study on primary culture of isolated proximal convoluted tubules. 246 62

Bronchoalveolar lavage (BALF) was found to be a useful index of cell damage. It has been observed that the enzymes in BALF could give an idea of cell damage in a pulmonary disease. Acid phosphatase, alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl-transpeptidase were assessed in mild, moderate, and severe pulmonary tuberculosis patients and Mantoux-negative normal controls. Activities of these enzymes were found to be higher in patients and were increasing with the severity of the disease. Increase in these enzymes in pulmonary tuberculosis patients could be attributed to lung tissue damage.
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PMID:Enzyme levels in bronchoalveolar lavage fluid and serum of active pulmonary tuberculosis patients. 256 25


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