Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.26 (invertase)
 4,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral administration of the antiulcerogenic drug, cimetidine, was studied on kidney-bound hydrolytic enzymes at three different dose levels (30 mg, 100 mg, and 2000 mg/kg body weight) and for single administration for 2 and 24 h, and daily administration for 15 days in mice. It significantly inhibited Na+, K(+)-ATPase, Mg(2+)-ATPase, and Ca2+, Mg(2+)-ATPase in the isolated basolateral membrane (BLM). Brush-border-membrane-(BBM)-associated enzymes, sucrase, lactase, maltase, leucine aminopeptidase, and alkaline phosphatase also showed a marked reduction. Substrate saturation kinetics revealed the nature of inhibition was of mixed type in the case of sucrase, lactase, maltase, and alkaline phosphatase (Km was increased, while Vmax decreased), whereas it was of non-competitive type for leucine aminopeptidase (Km was unchanged, while Vmax decreased). In vitro addition of cimetidine (5-20 mM) to the BBM also inhibited the enzyme activity. Dixon plot produced the inhibition constant (Ki) for cimetidine in the case of maltase, alkaline phosphatase, and leucine aminopeptidase in the order of 14.83, 32.83 and 11.5 mM, respectively. Analysis of lipids revealed a significant reduction in BBM-associated phospholipid and phospholipid/cholesterol molar ratio, while the neutral lipid fraction, i.e., cholesterol and triglycerides were not altered. Free fatty acid exhibited an increase after drug treatment, which was significant at higher dose after 24 h of single and 15 days of daily treatment. BLM-associated lipids did not exhibit any significant change. Cimetidine-induced depression in renal BLM- and BBM-associated disaccharidases and ATPases, at least at the higher dose level, may have serious consequences in the absorption of end-product nutrients.
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PMID:Depression of membrane-bound hydrolases by cimetidine in mouse renal basolateral and brush border. 183 34

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