Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloroacetaldehyde-modified poly(rC) or poly(dC) was prepared containing either 8-36% 3,N4-ethenocytidine (epsilon C) or 8-36% of a mixture of epsilon C and the hydrated epsilon C (epsilon C . H2O), with the hydrate greatly predominating (greater than 90%). These ribo- and deoxyribonucleotide templates were transcribed with DNA-dependent RNA polymerases from Escherichia coli and calf thymus, in the presence of either Mn2+ or Mg2+ and all four ribonucleoside triphosphates. All the polymers tested were transcribed with either cation present. In an earlier report from this laboratory [Spengler, S., & Singer, B. (1981) Nucleic Acids Res. 9. 365], transcriptional ambiguities resulting from epsilon C residues in enzymatically synthesized poly(rC, epsilon rC) were studied with E. coli DNA-dependent RNA polymerase in the presence of Mn2+. The misincorporations there reported were confirmed when poly(rC, epsilon rC) and poly(dC, epsilon dC), prepared by reaction of poly(rC) and poly(dC) with CAA, were transcribed in the presence of either Mn2+ or Mg2+. We now report that the presence of hydrated epsilon C in polymers also leads to misincorporations but with reproducible differences from those found with epsilon C alone. Nearest-neighbor analysis of the transcription products showed that the hydrate caused misincorporation of A greater than U much greater than C while epsilon C caused misincorporation of U greater than A much greater than C. The extent of misincorporation in transcription was less with Mg2+ than with Mn2+, but the pattern of ambiguity was the same with both cations and with both ribo- and deoxyribocytidylate polymers. Calf thymus DNA-dependent RNA polymerase IIB was also used to transcribe deoxyribocytidine polymers with Mn2+ as the cation. epsilon C and epsilon C . H2O both caused a high level of misincorporation of U , A, and C, but the preferred misincorporations differed slightly from those found with E. coli DNA-dependent RNA polymerase. For both prokaryotic and eukaryotic enzymes, the type of misincorporation resulting from the loss of hydrogen bonding by modification of the N-3 of C not only differed between epsilon C and the hydrated intermediate but also both differed from the transcriptional errors resulting from the presence of 3-methylcytidine in poly(dC) or poly(rC). We conclude that the errors made by these polymerases during transcription do not result primarily from the conditions used (cation, ribo- or deoxyribotemplate) but must be at least in part attributed to the enzyme recognizing some facet of the modified base other than the lack of normal hydrogen bonding.
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PMID:Chloroacetaldehyde-treated ribo- and deoxyribopolynucleotides. 2. Errors in transcription by different polymerases resulting from ethenocytosine and its hydrated intermediate. 675 74

PI is an important precursor for polyphosphoinositides and some sphingolipids and is also involved in the glycolipid anchoring of plasma membrane proteins. This lipid is synthesized from CDP-diacylglycerol and myo-inositol by PI synthase, an enzyme localized in the outer mitochondrial membranes and microsomes in yeast. PI synthase was highly purified from yeast microsomes after solubilization with Triton X-100. The activity is dependent on Mn2+ or Mg2+ and Triton X-100. The reaction follows a sequential Bi-Bi mechanism with binding to CDP-diacylglycerol before myo-inositol and releasing PI prior to CMP. Unlike most of the yeast phospholipid-synthesizing enzymes, PI synthase is a constitutive enzyme. Its expression is insensitive to the addition of myo-inositol and choline to culture medium or the transition of growth phase. The primary translate deduced from the encoding gene, PIS, comprises 220 amino acid residues with a calculated molecular mass of 23,613. The sequence contains several hydrophobic regions and resembles that of the human enzyme. The sequence also contains the local, conserved region found in enzymes catalyzing the transfer of the phosphoalcohol moiety from CDP-alcohol, such as phosphatidylserine synthase, cholinephosphotransferase and phosphatidylglycerolphosphate synthase. Substitution of amino acid at position 114 from His (CAC) to Gln (CAA) results in a 200-fold increase in Km of the enzyme for myo-inositol, making cells auxotrophic for myo-inositol. Disruption of the PIS locus in the genome is lethal, indicating that PI is essential for the survival and growth of yeast cells.
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PMID:Phosphatidylinositol synthase from yeast. 937 Mar 30

The administration of cisplatin (CDDP) may influence trace metal concentrations in body fluids. In order to test this hypothesis, the blood concentrations of trace metals were determined during the present study in eight Japanese esophageal and lung cancer patients receiving CDDP-based chemotherapy. The levels of manganese, iron (Fe), cobalt, copper, zinc (Zn), platinum and lead in the plasma were determined by inductively coupled plasma-mass spectrometry. In addition, the serum levels of Fe, transferrin and ferritin were evaluated. The baseline plasma concentration of Fe in patients with esophageal cancer was significantly lower than that in lung cancer patients (P=0.011), although there were no significant differences identified with respect to the plasma levels of other trace metals. The data obtained from six fasting patients without blood transfusion demonstrated that plasma concentrations of Fe increased 3.5-fold soon after CDDP treatment and returned to baseline levels ~10 days after therapy. The excessive Fe levels in the bloodstream induced changes in serum ferritin and transferrin levels. Furthermore, serum Zn levels increased 1.8-fold in the 1-3 days following CDDP treatment, and serum cystatin C levels transiently increased. These findings indicate that serum Fe and Zn levels may be useful to understanding the physiological responses in the early stages of CDDP-based chemotherapy, which may be associated with systemic inflammation and/or tissue distribution of CDDP.
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PMID:Changes in blood concentrations of trace metals in cancer patients receiving cisplatin-based chemotherapy. 2810 41