Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nucleotide pyrophosphatase activity with uridine diphosphoglucose and dephospho-CoA as substrates was demonstrated in normal human serum. The enzyme has a pH-optimum of about 9.6 and is inhibited by EDTA. Phosphodiesterase I (hydrolysis of thymidine-5'-monophospho-p-nitrophenylester) was also found in normal human serum, with a pH-optimum of about 9.8 and a Km of 0.20-0.25 mM. Probably both activities should be attributed to one enzyme. Different isoenzymes may exist, however. The activity of nucleotide pyrophosphatase/phosphodiesterase I in normal serum in many respects resembles an enzyme previously isolated from liver plasma membranes. Phosphodiesterase I activity was increased in normal pregnancy, in primary biliary cirrhosis, and in patients with bone lesions, but not in acute viral hepatitis or active chronic hepatitis. In primary biliary cirrhosis, the activity of phosphodiesterase I paralleled an increase of alkaline phosphatases.
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PMID:Nucleotide pyrophosphatase and phosphodiesterase I. Demonstration of activity in normal serum, and an increase in cholestatic liver disease. 0 80

The clinical usefulness of serum 5'-nucleotide phosphodiesterase isozyme-V (5'-NPD-V) assay as a serological marker for hepatocellular carcinoma was evaluated. Serum levels of 5'-NPD-V were measured by polyacrylamide gel electrophoresis in 536 Japanese patients with various diseases, including 120 patients with hepatocellular carcinoma. Icteric serum was not an indicator for the measurement of this isozyme, because jaundice gave a non-specific false-positive reaction. In 99 cases of hepatocellular carcinoma without jaundice, 73 (74%) had positive 5'-NPD-V and 24 (24%) showed levels greater than (+ +). The diagnostic value of this isozyme for hepatocellular carcinoma was relatively high, especially in patients with low or negative AFP levels. Diagnostic application for serum 5'-NPD-V assay to small liver tumors was limited. 5'-NPD-V showed false-positive results even in certain cases of benign liver diseases such as chronic hepatitis and liver cirrhosis, but cases with positivities stronger than (+ +) were few. Moreover, the test might be useful for the prediction of liver metastasis in cancer patients, since positive rates were significantly higher in cases with liver metastasis than in those in the non-liver metastasis group.
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PMID:5'-Nucleotide phosphodiesterase isozyme-V in hepatocellular carcinoma and other liver diseases. 170 10

Hepatitis B virus (HBV), the causative agent of chronic hepatitis B and prototypic hepadnavirus, is a small DNA virus that replicates by protein-primed reverse transcription. The product is a 3-kb relaxed circular DNA (RC-DNA) in which one strand is linked to the viral polymerase (P protein) through a tyrosyl-DNA phosphodiester bond. Upon infection, the incoming RC-DNA is converted into covalently closed circular (ccc) DNA, which serves as a viral persistence reservoir that is refractory to current anti-HBV treatments. The mechanism of cccDNA formation is unknown, but the release of P protein is one mandatory step. Structural similarities between RC-DNA and cellular topoisomerase-DNA adducts and their known repair by tyrosyl-DNA-phosphodiesterase (TDP) 1 or TDP2 suggested that HBV may usurp these enzymes for its own purpose. Here we demonstrate that human and chicken TDP2, but only the yeast ortholog of TDP1, can specifically cleave the Tyr-DNA bond in virus-adapted model substrates and release P protein from authentic HBV and duck HBV (DHBV) RC-DNA in vitro, without prior proteolysis of the large P proteins. Consistent with TPD2's having a physiological role in cccDNA formation, RNAi-mediated TDP2 depletion in human cells significantly slowed the conversion of RC-DNA to cccDNA. Ectopic TDP2 expression in the same cells restored faster conversion kinetics. These data strongly suggest that TDP2 is a first, although likely not the only, host DNA-repair factor involved in HBV cccDNA biogenesis. In addition to establishing a functional link between hepadnaviruses and DNA repair, our results open new prospects for directly targeting HBV persistence.
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PMID:Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses. 2520 58