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

We previously described a lyophilized supernatant from germinated Candida albicans that blocks human neutrophil (PMN) O2- production and degranulation stimulated by several PMN agonists but does not block stimulation by PMA. In studies to further characterize this Candida hyphal inhibitory product (CHIP), we noted several physicochemical parallels with the purine nucleoside adenosine (Ado). A Sephadex G-10 semipurified fraction of CHIP had an absorption peak near 260 nm, an apparent m.w. of less than 400, and was resistant to boiling and proteases. Maximally effective doses of CHIP (100 micrograms/ml) and Ado (100 microM) blocked 0.1 microM FMLP-stimulated O2- production by 76.8 +/- 4.1 and 81.7 +/- 4.8%, respectively. Ado deaminase, known to inactivate Ado, reversed inhibition by both Ado and CHIP. Results were comparable for the effect of CHIP and Ado on FMLP-stimulated beta-glucuronidase and lactoferrin release. Activation of the respiratory burst by opsonized C. albicans yeast was also inhibited by CHIP and Ado, but the extent of inhibition was less than for FMLP. At yeast:PMN ratios of 4:1, 10:1, and 40:1, CHIP inhibited O2- by -3.8%, 14.3%, and 12.8%, respectively; Ado blocked production by 32.9%, 24.2%, and 11.5%, respectively. The effect of CHIP and Ado on Candida killing by PMN was compared using two viability assays in each of four experiments. Ado (100 microM) had no effect on killing, although CHIP (100 micrograms/ml) inhibited killing in the MTT assay at 15 and 45 min by 81.6 +/- 6.3 and 24.7 +/- 6.2%, respectively; as assayed by CFU, CHIP inhibited killing by 34.1 +/- 6.2 and 10.3 +/- 2.5%, respectively. The ability of CHIP to inhibit killing was not affected by adding Ado deaminase, providing additional evidence that an Ado-like effect by CHIP is not essential for killing inhibition. Killing of opsonized Streptococcus pneumoniae was also inhibited in a concentration-dependent manner. Reverse-phase HPLC of the semipurified fraction revealed a peak, eluting identically to authentic Ado, which was eliminated by adding Ado deaminase. Ado content of the G-10 fraction was sufficient to account fully for the FMLP-inhibitory activity. The antikilling activity was resistant to boiling and proteases but was eliminated by mild periodation. Fractions eluting from a Sephadex CL6B column between 0.8 and 2.0 x 10(6) m.w. had increased sp. act. for killing inhibition. Sp. act. increased as carbohydrate content increased, but killing inhibition by various Candida cell wall constituents was absent to modest compared to inhibition induced by CHIP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vitro, Candida albicans releases the immune modulator adenosine and a second, high-molecular weight agent that blocks neutrophil killing. 131 20

Arachidonylethanolamide (anandamide, AEA) has been identified as an endogenous ligand for cannabinoid receptors CB1 and CB2. Characterization of the direct cannabimimetic actions of anandamide has been hampered by its short duration of action and rapid degradation in in vivo and in vitro systems to arachidonic acid, a precursor in the biosynthesis of a broad range of biologically active molecules. In the present studies, we utilized 2-methylarachidonyl-(2'-fluoroethyl)amide (F-Me-AEA), an analog of anandamide resistant to enzymatic degradation, to determine whether F-Me-AEA modulated T cell function similar to that of plant-derived cannabinoids. Indeed, F-Me-AEA at low micromolar concentrations exhibited a marked inhibition of phorbol ester plus calcium ionophore (PMA/Io)-induced IL-2 protein secretion and steady state mRNA expression. Likewise, a modest suppression of the mixed lymphocyte response was observed in the presence of F-Me-AEA indicating an alteration in T cell responsiveness to allogeneic MHC class II antigens. F-Me-AEA was also found to modestly inhibit forskolin-stimulated adenylate cyclase activity in thymocytes and splenocytes, a hallmark of cannabinoid receptor agonists. Further characterization of the influence of F-Me-AEA on the cAMP signaling cascade revealed an inhibition of CREB-1/ATF-1 phosphorylation and subsequently, an inhibition of CRE DNA binding activity. Characterization of nuclear binding proteins further revealed that NF-AT and, to a lesser extent, NF-kappaB DNA binding activities were also suppressed. These studies demonstrate that F-Me-AEA modulates T cell function in a similar manner to plant-derived and endogenous cannabinoids and therefore can be utilized as an amidase- and hydrolysis-resistant endogenous cannabinoid.
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PMID:Inhibition of leukocyte function and interleukin-2 gene expression by 2-methylarachidonyl-(2'-fluoroethyl)amide, a stable congener of the endogenous cannabinoid receptor ligand anandamide. 1589 38

The amidase reaction of trypsin, which is a member of the serine proteinase family, is accelerated by its complexation with block ionomers containing a polycarboxylate block, such as PEG-PAA, PEG-PGA, or PEG-PMA. PEG-PAA and PEG-PGA had similar effects, causing an increase in the k(cat) value and a shift in the pH profile to a lower pH region. On the other hand, PEG-PMA showed not only an increase in the k(cat) value, but also a decrease in the activation energy; however, there was no shift in the pH dependence of the initial reaction rate. Such differences might be induced by the difference in pK(a) values of the polycarboxylate block in block ionomers.
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PMID:Effect of polycarboxylate blocks on the amidase activity of trypsin through complexation with PEG/polycarboxylate block ionomers. 1737 Feb 72