Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several enzymes were investigated histochemically in the colons of normal male F344 rats in order to understand the function of different types of cells in this tissue. Serial methacrylate-embedded sections (2-4 microns) allowed the precise localizations of several enzymes including acid phosphatase, alkaline phosphatase, gamma-glutamyl transpeptidase, N-acetyl-beta-D-glucosaminidase (hexosaminidase), alpha-naphthyl butyrate esterase and 5'-nucleotidase. Sites reactive with periodic acid-Schiff were also localized. Gradients of enzyme activity were observed between caecum and rectum and/or from the luminal surfaces to the bases of the crypts for hexosaminidase, esterase and gamma-glutamyl transpeptidase. To our knowledge this is the first histochemical demonstration of gamma-glutamyl transpeptidase in normal rat colonic epithelial cells. The utilization of the methacrylate-embedding technique has revealed previously undescribed gradients of enzyme activity and has allowed the localization of enzyme activities not previously reported in normal rat colonic mucosa.
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PMID:In situ localization of enzymes and mucin in normal rat colon embedded in plastic. 247 20

Interest in the role of mononuclear phagocytes in glomerulonephritis (GN) and in defining markers of renal neoplasms led the authors to study alpha-naphthyl acetate/butyrate esterase (ANAE/ANBE), alkaline phosphatase (AlkP), acid phosphatase (AcP), 5'-nucleotidase (5'N), and ATPase (ATP) activity in paraformaldehyde-fixed, plastic-embedded renal tissue from patients with a variety of pathologic conditions. These conditions included GN, renal tumors, and transplant rejection. Enzymatic staining for ANAE, ANBE, AcP, AlkP, and ATP was generally confined to tubules and collecting ducts in normal kidney. Nine of 10 cases of renal carcinoma had weakly to strongly positive reactions with AlkP, AcP, and ANAE; 9 of 10 cases of Wilms' tumor showed weakly positive reactions with AcP and ANAE, particularly in tubular structures. Severely damaged kidney allografts showed surprising retention of normal histochemical features. In all cases 5'N stained both glomerular capillaries and interstitial vasculature; ATPase and AlkP stained interstitial vessels only. Plastic embedding provides superb preservation of both microscopic anatomy and enzymatic activity, which may allow utilization of enzyme histochemistry for diagnostic and research purposes.
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PMID:Enzyme histochemistry in plastic-embedded sections of normal and diseased kidneys. 258 40

F344 Male rats weighting between 90 and 110 gm were given 90 ppm diethylnitrosamine in their drinking water for 5 weeks. Seven weeks after the administration of carcinogen was completed, the rats were sacrificed and sections of their livers were embedded in methacrylate. Serial sections 2 or 4 micron in thickness demonstrated the presence of gamma-glutamyl transpeptidase, acid phosphatase, adenosine triphosphatase, aldehyde dehydrogenase, alkaline phosphatase, alpha-naphthyl butyrate esterase, DT diaphorase, glucose-6-phosphate dehydrogenase, and 5'-nucleotidase activity and glycogen. The use of 4-micron sections of methacrylate-embedded tissue allows the evaluation of many more phenotypic markers in serial sections than is currently possible with frozen sections.
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PMID:Examination of enzyme-altered foci with gamma-glutamyl transpeptidase, aldehyde dehydrogenase, glucose-6-phosphate dehydrogenase, and other markers in methacrylate-embedded liver. 287 68

Two-micrometer sections of methacrylate-embedded kidney were used to investigate the enzymatic activities of mouse kidney where the proximal tubule and Bowman's capsule from the same corpuscle were viewed in the same section. Alkaline phosphatase, acid phosphatase, 5'-nucleotidase, gamma-glutamyl transpeptidase, N-acetyl-beta-glucosaminidase, leucine aminopeptidase, alpha-naphthyl butyrate esterase, and adenosine triphosphatase activities were observed in the proximal tubule, but only 5'-nucleotidase, alpha-naphthyl butyrate esterase, and alkaline phosphatase were observed in the squamous portion of the parietal epithelium of Bowman's capsule. The use of methacrylate-embedded tissue allowed more precise localization of enzymatic activity than is possible with most frozen sections. This may provide interesting applications not only for characterization of kidney diseases but also for characterization of other normal and abnormal tissues.
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PMID:Enzymatic histochemistry of mouse kidney in plastic. 288 Aug 90

The bis[(pivaloyloxy)methyl] [PIV2] derivative of 2'-deoxy-5- fluorouridine 5'-monophosphate (FdUMP) was synthesized as a potential membrane-permeable prodrug of FdUMP. The compound was designed to enter cells by passive diffusion and to revert to FdUMP after removal of the PIV groups by hydrolytic enzymes. The most convenient preparation of PIV2FdUMP was by condensation of 2'-deoxy-5-fluorouridine (FUdR) with PIV2 phosphate in the presence of triphenylphosphine and diethyl azodicarboxylate (the Mitsunobo reagent). PIV2FdUMP was stable in the pH range 1.0-4.0 (t1/2 > 100 h). It was also fairly stable at pH 7.4 (t1/2 = 40.2 h). In 0.05 M NaOH solution, however, it was rapidly degraded (t1/2 < 2 min). In the presence of hog liver carboxylate esterases, PIV2FdUMP was converted quantitatively to the mono-[(pivaloyloxy)methyl] [PIV1] analogue PIV1FdUMP. After a 24 h incubation, only trace amounts of FdUMP (1-3%) were observed, indicating that PIV1FdUMP is a poor substrate for carboxylate esterases. In mouse plasma, PIV2FdUMP was rapidly metabolized, first to PIV1FdUMP and then to FdUMP. With continued incubation, FUdR was formed, presumably due to further catabolism of FdUMP by plasma phosphatases or 5'-nucleotidases. Since PIV1FdUMP is a poor substrate for carboxylate esterase, the cleavage of the second PIV group is most likely mediated by plasma phosphodiesterases. The rate of degradation of PIV2FdUMP in the presence of acid and alkaline phosphatase, 5'-nucleotidase, or spleen phosphodiesterase was the same as that in buffer controls, indicating that the compound is not a substrate for these nucleotide catabolizing enzymes. The concentration of PIV2FdUMP and its 3'-O-acetyl ester (PIV2 3'-O-Ac-FdUMP) required to inhibit the growth of Chinese hamster ovary (CHO) cells in vitro to less than 50 cells per colony was 5 x 10(-6) M, the same as that required for 5-fluorouracil (FU). Both nucleotide prodrugs showed the same growth-inhibitory potency against a mutant CHO cell line that was 20-fold resistant to FU (CHO/FU). Administered intraperitoneally at optimal dosage for 5 consecutive days, PIV2FdUMP and PIV2 3'-O-Ac-FdUMP were as effective as FU at prolonging the life spans of mice bearing intraperitoneally implanted P388 leukemia. Both prodrugs retained full therapeutic activity against a P388 subline resistant to FU. Collectively, these data indicate that PIV2FdUMP and PIV2 3'-O-Ac-FdUMP are effective membrane-permeable prodrugs of FdUMP.
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PMID:Synthesis and antitumor evaluation of bis[(pivaloyloxy)methyl] 2'-deoxy-5-fluorouridine 5'-monophosphate (FdUMP): a strategy to introduce nucleotides into cells. 796 51

The absorption enhancement and presystemic degradation kinetics of a homologous series of acyclovir 2'-ester prodrugs were investigated in rats using the in situ nasal perfusion technique in the presence of bile salt-fatty acid mixed micelles. In vitro incubation studies indicated that nasal perfusate containing a mixed micellar solution generated higher ester-cleaving activity than isotonic phosphate buffer washings. Inhibitor screening and substrate specificity studies demonstrated the enzyme to be most likely carboxylesterase rather than true cholinesterase. The extent of prodrug cleavage by the carboxylesterase appears to correlate well with the substrate lipophilicity for esters with linear acyl chains. On the other hand, branching of the acyl side chain significantly retards acyclovir prodrug breakdown. To estimate the nasal epithelial membrane and cytoplasmic damaging effect caused by sodium glycocholate (NaGC)-linoleic acid (15 mM:5 mM) mixed micelles, the release profiles of 5'-nucleotidase (5'-ND), lactate dehydrogenase (LDH), and carboxylesterase in the nasal perfusate were measured as a function of time. The results indicated that the activities of all three enzymes resulting from the mixed micellar solution appeared to be significantly higher than those caused by 15 mM NaGC alone. The apparent nasal absorption rate constants of acyclovir and its butyrate, valerate, pivalate, and hexanoate ester prodrugs in mixed micellar solutions containing an esterase inhibitor (1 mM phenylmethylsulfonyl fluoride) were individually calculated. Without an inhibitor, lengthening of the linear acyl side chain of the prodrug resulted in greatly accelerated degradation coupled with moderate absorption improvement. The solubilities and micellar binding constants of acyclovir prodrugs were also determined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bile salt-fatty acid mixed micelles as nasal absorption promoters. III. Effects on nasal transport and enzymatic degradation of acyclovir prodrugs. 816 83