Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Few reports have dealt with the kinetics and metabolism of AraC and analogs by rat intestine. Using everted rat jejunum with continuous perfusion, it was possible to demonstrate that AraC and Cyd cross the intestinal barrier(s) by a carrier mediated process which was saturable and exhibited fairly good fitting of the flux rate by Michaelis-Menten equation. The transport rate of different analogs was not consistent with the pH-partition theory of membrane transport of drugs being rather dependent on the chemical structure of the nucleoside. A free amino group of cytosine increased the rate of transport within the present series of AraC analogs. There was a detectable deaminase as well as esterase activity towards AraC and its analogs in rat jejunum.
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PMID:Kinetics of transport and metabolism of 1-beta-D-arabinofuranosylcytosine and structural analogs by everted perfused rat jejunum. 670 82

2-Chlorodeoxyadenosine (CdA) is a deaminase-resistant purine analogue which has shown clinical activity against various haematological tumours, and is currently undergoing phase II trials. In the present study, the semiautomated fluorometric microculture cytotoxicity assay (FMCA) was used for in vitro evaluation of CdA activity in cell suspensions from both haematological and solid tumours. A total of 133 samples from various diagnoses were successfully tested with continuous drug exposure. CdA showed high in vitro activity against samples from chronic and acute lymphocytic leukaemia and acute myelocytic leukaemia, but little or no response was observed in the solid tumour groups. Cross-resistance analysis with standard drugs revealed the following rank order of correlation coefficients: cytosine arabinoside (AraC) > daunorubicin > doxorubicin > vincristine > prednisolone > 4-hydroperoxycyclophosphamide > etoposide > cisplatin. The high correlation between CdA and AraC was maintained even if the analysis was based only on the haematological tumours. The results indicate that CdA is differentially active against haematological tumours with little or no activity against solid tumours. CdA also appears highly cross resistant with AraC. If this disease-specific information is substantiated in further clinical trials and extended to other phase I-II drugs, non-clonogenic drug resistance assays such as the FMCA may become useful in new drug evaluation, and in targeting specific diagnoses and patients for phase II trials.
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PMID:In vitro activity of 2-chlorodeoxyadenosine (CdA) in primary cultures of human haematological and solid tumours. 794 67

Coproporphyrinogen III oxidase, an enzyme involved in heme biosynthesis, catalyzes the oxidative decarboxylation of coproporphyrinogen III to form protoporphyrinogen IX. Genetic and biochemical studies suggested the presence of two different coproporphyrinogen III oxidases, one for aerobic and one for anaerobic conditions. Here we report the cloning of the hemF gene, encoding the aerobic coproporphyrinogen III oxidase from Escherichia coli, by functional complementation of a Saccharomyces cerevisiae HEM13 mutant. An open reading frame of 897 bp encoding a protein of 299 amino acids with a calculated molecular mass of 34.3 kDa was identified. Sequence comparisons revealed 43% amino acid sequence identity with the product of the S. cerevisiae HEM13 gene and 90% identity with the product of the recently cloned Salmonella typhimurium hemF gene, while a structural relationship to the proposed anaerobic enzyme from Rhodobacter sphaeroides was not obvious. The hemF gene is in an operon with an upstream open reading frame (orf1) encoding a 31.7-kDa protein with homology to an amidase involved in cell wall metabolism. The hemF gene was mapped to 52.6 min of the E. coli chromosome. Primer extension experiments revealed a strong transcription initiation site upstream of orf1. A weak signal, possibly indicative of a second promoter, was also identified just upstream of the hemF gene. A region containing bent DNA (Bent 111), previously mapped to 52.6 min of the E. coli chromosome, was discovered in the 5' region of orf1. Two potential integration host factor binding sites were found, one close to each transcription start site. An open reading frame (orf3) transcribed in a direction opposite that of the hemF gene was found downstream of the hemF gene. It encodes a protein of 40.2 kDa that showed significant homology to proteins of the XylS/AraC family of transcriptional regulators.
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PMID:Isolation of the hemF operon containing the gene for the Escherichia coli aerobic coproporphyrinogen III oxidase by in vivo complementation of a yeast HEM13 mutant. 830 May 22

The importance of viridans streptococci as agents of serious extra-oral diseases, including endocarditis, is now recognized. We have tested the hypothesis that the ability to utilize sialic acid as a nutrient source may play a role in the proliferation of these organisms. The type strains of the 15 presently recognized species of viridans streptococci and two clinical isolates-S. oralis (AR3), isolated from a patient with infective endocarditis, and S. intermedius (UNS35), a brain abscess isolate-were studied for their ability to utilize sialic acid. Only S. oralis, S. sanguis, S. gordonii, S. mitis ("oralis group") S. intermedius, S. anginosus, S. constellatus ("milleri group"), and S. defectivus ("nutritionally variant group") were able to use sialic acid (N-acetylneuraminic acid) efficiently as a sole carbon source. Formate, acetate, and ethanol were produced as the major metabolic end-products of sialic acid metabolism, while corresponding glucose-grown cultures produced lactate as the major metabolic end-product. Utilization of sialic acid was independent of the production of sialidase. Cell-free extracts of sialic acid-grown cultures expressed elevated levels of N-acetylneuraminate pyruvate-lyase (NPL; the first enzyme in the intracellular catabolism of sialic acid) and N-acetylglucosamine-6-phosphate (GlcNAc-6-P) deacetylase and glucosamine-6-phosphate (GlcN-6-P) deaminase (enzymes involved in the intracellular catabolism of N-acetylglucosamine). These activities were repressed by growth in the presence of glucose. The intracellular fate of sialic acid, after cleavage by NPL into N-acetylmannosamine (ManNAc) and pyruvate, is uncertain, but the elevated levels of GlcNAc-6-P deacetylase and GlcN-6-P deaminase in sialic acid-grown cells suggest that phosphorylation and isomerization are possible steps in the metabolism of ManNAc to generate an intermediate common to the pathway of N-acetylglucosamine metabolism. The species of viridans streptococci that have the ability to utilize sialic acid are those most commonly associated with extra-oral diseases, and this ability is likely to play a role in the persistence and survival of these infecting organisms in vivo.
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PMID:Utilization of sialic acid by viridans streptococci. 890 24