Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent delineation of a clinical syndrome marked by eosinophilia, myalgia, and scleroderma-like skin changes associated with L-tryptophan use has necessitated the Centers for Disease Control to initiate a health alert. The likely association of L-tryptophan ingestion with a syndrome that mimics eosinophilic fasciitis (Shulman's syndrome) further identifies an environmental agent associated with an inflammatory sclerosing rheumatic disease process. In this report, we present the clinical, morphologic, and enzyme histochemical findings in muscle, skin, and fascia biopsies from 14 cases fulfilling the Center for Disease Control diagnostic criteria for L-tryptophan-associated eosinophilia-myalgia syndrome. The clinical syndrome reveals a high incidence of arthralgia, elbow contracture, and clinical neuropathy. The absence of significant change in creatine kinase or sedimentation rate allows for diagnostic separation from other inflammatory myopathies. Histoenzymatic features in muscle biopsies reveal a preferential epimysial-perimysial noneosinophilic infiltration characterized by acid phosphatase reactive histiocytosis, nonnecrotizing venulitis, perineural inflammation within dermis and perimysium, type II fiber atrophy with superimposed denervation features, and perifascicular alkaline phosphatase reactivity representing early neofibroplasia. The constellation of changes in skin, fascia, and muscle, with the defined clinical syndrome, allows for accurate differentiation from allied syndromes, including eosinophilic polymyositis, scleroderma, idiopathic polymyositis/dermatomyositis, polyarteritis nodosa, and toxic oil syndrome. Accurate differentiation from eosinophilic fasciitis still rests on a history of L-tryptophan ingestion.
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PMID:Neuromuscular manifestations of L-tryptophan-associated eosinophilia-myalgia syndrome: a histomorphologic analysis of 14 patients. 198 74

We have used an alkaline phosphatase protection assay to investigate the interaction of the trp repressor with its operator sequence. The assay is based on the principle that the trp repressor will protect a terminally 5'-32P-labeled operator DNA fragment from attack by alkaline phosphatase. The optimal oligonucleotide for investigating the trp repressor/operator interaction extends two base pairs from each end of the genetically defined target sequence predicted by in vivo studies [Bass et al. (1987) Genes Dev. 1, 565-572]. The assay works well over a 10,000-fold range of protein/DNA affinity and is used to show that the corepressor, L-tryptophan, causes the liganded repressor to bind a 20 base pair trp operator duplex 6400 times more strongly than the unliganded aporepressor. The affinity of the trp repressor for operators containing symmetrical mutations was interpreted in terms of the trp repressor/operator crystal structure as follows: (1) Direct hydrogen bonds with the functional groups of G-9 of the trp operator and the side chain of Arg 69 of the trp repressor contribute to DNA-binding specificity. (2) G-6 of the trp operator is critical for DNA-binding specificity probably because of the two water-mediated hydrogen bonds between its functional groups and the N-terminus of the trp repressor's E-helix. (3) Sequence-dependent aspects of the trp operator's conformation help stabilize the trp repressor/operator complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An alkaline phosphatase protection assay to investigate trp repressor/operator interactions. 198 82

The clinical constellation of leukocytosis, thrombocytosis, and low or absent stainable neutrophil alkaline phosphatase (NAP) is considered characteristic of chronic myelogenous leukemia (CML). CML with eosinophilic differentiation (eosinophilic leukemia) is well described, and leukemia and other clonal hematologic malignancies are associated with the syndrome of eosinophilic fasciitis. We describe leukocytosis, thrombocytosis, eosinophilia, mild basophilia, and absent stainable NAP, initially suggesting the diagnosis of CML in a patient with the eosinophilia myalgia syndrome associated with L-tryptophan use, a condition resembling eosinophilic fasciitis. Cytogenetic and molecular genetic studies failed to demonstrate a clonal proliferation of eosinophils.
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PMID:Absent neutrophil alkaline phosphatase in the eosinophilia myalgia syndrome associated with L-tryptophan use. 201 75

Many proteins are now known to be anchored to the plasma membrane by a phosphatidylinositol-glycan (PI-G) moiety that is attached to their COOH termini. Placental alkaline phosphatase (PLAP) has been used as a model for investigating mechanisms involved in the COOH-terminal processing of PI-G-tailed proteins. The COOH-terminal domain of pre-pro-PLAP provides a signal for processing during which a largely hydrophobic 29-residue COOH-terminal peptide is removed, and the PI-G moiety is added to the newly exposed Asp-484 terminus. This cleavage/attachment site was subjected to an almost saturation mutagenesis, and the enzymatic activities, COOH-terminal processing, and cellular localizations of the various mutant PLAP forms were determined. Substitution of Asp-484 by glycine, alanine, cysteine, asparagine, or serine (category I) resulted in PI-G-tailed and enzymatically active proteins. However, not all category I mutant proteins were PI-G tailed to the same extent. Pre-pro-PLAP with other substituents at position 484 (threonine, proline, methionine, valine, leucine, tyrosine, tryptophan, lysine, glutamic acid, and glutamine; category II) were expressed, as well as the category I amino acids, but there was little or no processing to the PI-G-tailed form, and this latter group exhibited very low enzyme activity. The bulk of the PLAP protein produced by category II mutants and some produced by category I mutants were sequestered within the cell, apparently in the endoplasmic reticulum (ER). Most likely, certain amino acids at residue 484 are preferred because they yield better substrates for the putative "transamidating" enzyme. In transfected COS cells, at least, posttranslational PI-G-tail processing does not go to completion even for preferred substrates. Apparently PI-G tailing is a requisite for transport from the ER and for PLAP enzyme activity. Proteins that are not transamidated are apparently retained in the ER in an inactive conformation.
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PMID:Selectivity of the cleavage/attachment site of phosphatidylinositol-glycan-anchored membrane proteins determined by site-specific mutagenesis at Asp-484 of placental alkaline phosphatase. 215 84

Osteogenic tumours from c-fos (MT-c-fos-LTR)-transgenic mice and from mice infected with the v-fos-bearing FBR murine osteosarcoma virus (FBR MSV) showed close morphological and neoplastic similarities. Fos mRNA expression was elevated in both types of tumours, and expression of several genes characteristic of differentiated bone cells was either lower, enhanced, or not detectable in comparison to that in normal bone. Tumour-derived cell lines showed variable levels of exogenous fos expression; bone-cell-specific genes were similarly expressed in both primary tumours and tumour-derived cell lines. Upon transplantation the tumour cells formed fibrosarcomas, some of which contained areas of focal osseochondrous differentiation. Non-tumorigenic cell lines established from bone tissue of normal and MT-c-fos-LTR transgenic mice showed osteoblastic characteristics, whereas no parathyroid hormone (PTH) response was observed in transgenic tumour cell lines in spite of high alkaline phosphatase activity. These data indicate that deregulated fos expression interferes with terminal osteogenic differentiation in v-fos- and c-fos-induced bone tumours.
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PMID:Characterization of fos-induced osteogenic tumours and tumour-derived murine cell lines. 217 37

The far-ultraviolet circular dichroism spectra of fibrinogens phosphorylated by protein kinase C or casein kinase II indicated a conformational change corresponding to an increase in ordered secondary structure. The spectra of protein kinase A- or casein kinase I-phosphorylated fibrinogens did not differ substantially from the control. Fluorescence studies indicated changes in the tertiary structure around tryptophan residues for protein kinase A- or C-phosphorylated fibrinogens, but failed to show any such change for fibrinogen phosphorylated by either of the casein kinases. This latter result was also confirmed by circular dichroism measurements in the near-ultraviolet region. The apparent increase in ordered structure was proposed as an explanation for the slower rate of plasmin degradation seen in fibrinogens after phosphorylation by protein kinase C [6], and casein kinase II, especially as both spectral changes and plasmin degradation rate were unaffected by alkaline phosphatase.
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PMID:Conformational changes in human fibrinogen after in vitro phosphorylation and their relation to fibrinogen behaviour. 222 21

We report on two brothers with renal hypophosphatemia, intracerebral calcifications, minor facial anomalies, and short distal phalanges. The children presented with recurrent dental abscesses; one had premature closure of the anterior fontanelle. Biochemical findings included hypophosphatemia and elevated serum alkaline phosphatase with normocalcemia. Blood levels of parathyroid hormone, 1,25(OH)2 and 25(OH) vitamin D levels were normal; TRP (the fractional tubular reabsorption of PO4) and TmP/GFR (the tubular maximum rate of PO4 reabsorption in relation to GFR) were low. Both parents had a normal serum phosphate and brain CT scan without evidence of calcifications. This apparently new syndrome of renal hypophosphatemia associated with intracerebral calcifications appears to be inherited as either an autosomal recessive or an X-linked trait.
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PMID:Familial renal hypophosphatemia, minor facial anomalies, intracerebral calcifications, and non-rachitic bone changes: apparently new syndrome? 230 90

Acute morphine produced a dose-dependent, naloxone-sensitive, reversible increase in tryptophan hydroxylase activity in low speed supernatants of midbrain, pons-medulla and cerebral cortex but not spinal cord. The increase in cortical enzyme activity was blocked by 6-hydroxydopamine pretreatment, could be reversed in vitro by incubation with alkaline phosphatase and was non-additive with the increase in enzyme activity induced in the presence of phosphorylating conditions. Morphine administration produced an increase in Vmax but no change in Km of cortical enzyme for substrate, tryptophan, or the artificial reduced pterin cofactor, 6-methyl-5,6,7,8-tetrahydropterin. The failure of morphine to increase spinal tryptophan hydroxylase activity despite enhancement of enzyme activity in medulla indicates regional differences in responsiveness of the enzyme to in vivo activation.
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PMID:Activation of cortical tryptophan hydroxylase by acute morphine treatment: blockade by 6-hydroxydopamine. 244 68

We describe a family with an inherited persistent elevation of serum alkaline phosphatase activity in the absence of malignant disease, observed for at least 15 yr. Isoenzyme studies revealed that this increased activity was due to an enzyme which showed similarities to serum placental alkaline phosphatase from pregnant women having the following properties: high heat stability; reactivity to anti-placental alkaline phosphatase antiserum; lack of inhibition by L-homoarginine; moderate inhibition by EDTA; and lack of interaction with wheat germ lectin. The enzyme was less sensitive than placental alkaline phosphatase to inhibition by L-phenylalanine, L-tryptophan, L-leucine, L-leucyl-glycyl-glycine and L-phenylalanyl-glycyl-glycine. The enzyme also differed from the placental alkaline phosphatase in its electrophoretic mobility, isoelectric heterogeneity and apparent molecular mass. We conclude that the enzyme is an inherited heat stable alkaline phosphatase variant which might correspond to a rare phenotype of placental alkaline phosphatase.
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PMID:Inherited occurrence of a heat stable alkaline phosphatase in the absence of malignant disease. 250 Oct 47

Surface enhanced Raman scattering (SERS) of some enzymes (alkaline phosphatase, horseradish peroxidase and lactoperoxidase) and some amino acids (tryptophan, tyrosine and phenylalanine) on silver electrodes has been studied. The spectral band intensities of certain amino acids and amino acid residues were determined by their orientation on the surface and depended on the electrode potential (E).
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PMID:Structure-potential dependence of adsorbed enzymes and amino acids revealed by the surface enhanced Raman effect. 275 91


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