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 gene encoding the mouse placental alkaline phosphatase (ALP; orthophosphoric-monoester phosphohydrolase, alkaline optimum, EC 3.1.3.1) is mapped to chromosome 4, based on Southern blot hybridization of the mouse cDNA with DNAs from mouse-Chinese hamster somatic cell hybrids. This assignment is consistent with the genetic analysis of the Akp-2 locus, which is responsible for the genetic variation of alkaline phosphatase enzyme in placenta as well as in liver, kidney, and bone.
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PMID:Mapping of gene encoding mouse placental alkaline phosphatase to chromosome 4. 316 38

Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and a deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. Clinical severity is variable, ranging from death in utero (due to severe rickets) to pathologic fractures first presenting in adult life. Affected siblings, however, are phenotypically similar. Severe forms of the disease are inherited in an autosomal recessive fashion; heterozygotes often show reduced serum ALP activity. The specific gene defects in hypophosphatasia are unknown but are thought to occur either at the L/B/K ALP locus or within another gene that regulates L/B/K ALP expression. We used the polymerase chain reaction to examine L/B/K ALP cDNA from a patient with a perinatal (lethal) form of the disease. We observed a guanine-to-adenine transition in nucleotide 711 of the cDNA that converts alanine-162 of the mature enzyme to threonine. The affected individual, whose parents are second cousins, is homozygous for the mutant allele. Introduction of this mutation into an otherwise normal cDNA by site-directed mutagenesis abolishes the expression of active enzyme, demonstrating that a defect in the L/B/K ALP gene results in hypophosphatasia and that the enzyme is, therefore, essential for normal skeletal mineralization.
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PMID:A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. 317 60

The effectiveness of synthetic salmon calcitonin (SCT) administered as a nasal spray was assessed via clinical, biological, and radiological variables in 17 previously untreated Pagetic patients over a 1-year course of therapy. The results showed a highly significant decrease of serum alkaline phosphatase (S-ALP) (p less than 0.05 after 1 month of treatment) and of the urinary hydroxyproline/creatinine ratio (OH/Cr) (p less than 0.01 after 1 month of treatment). For the whole group, the mean decrease in S-ALP was 37 +/- 4% (SEM) after 6 months (p less than 0.01) and 31 +/- 5% after 1 year (p less than 0.01). The mean fall in OH/Cr was 35 +/- 6% (SEM) (p less than 0.01) and 37 +/- 7% (p less than 0.01) after 6 and 12 months, respectively. None of the usual side-effects of SCT were reported and local tolerance was excellent throughout the study.
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PMID:One year's treatment of Paget's disease of bone by synthetic salmon calcitonin as a nasal spray. 321 19

The cortical thickness of the clavicle (CTC), concentrations of bone gamma-carboxyglutamic acid-containing (Gla) protein (s-BGP, osteocalcin), alkaline phosphatase (s-ALP), calcium (s-Ca) and inorganic phosphorus (s-P) in serum, and calcium/creatinine (u-Ca/Cr) and inorganic phosphorus/creatinine (u-P/Cr) ratios in urine were examined in 211 subjects aged over 40 years in Oshima Island in Nagasaki prefecture. CTC decreased and s-BGP increased with age in both sexes, especially in women. Serum BGP was significantly higher in women than in men at the ages of 50's and over. Serum ALP in women increased until the ages of 60's. Serum Ca at the ages of 50's and s-P at the ages of 60's and over were higher in women than in men. As the increase in s-BGP is reported to be coincident with active bone formation, our findings do not support the view that age-related bone loss, especially in women, primarily results from decrease in bone formation.
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PMID:Changes in cortical thickness of the clavicle and serum bone gamma-carboxyglutamic acid-containing protein in the elderly in an island community in western Japan. 325 55

Changes in osteoblast function, assessed by serial bone scans and serum alkaline phosphatase bone isoenzyme (ALP-Bl) and osteocalcin, have been studied in 53 patients receiving systemic therapy for bone metastases from advanced breast cancer. In 12/16 patients with healing of lytic disease on x-ray a paradoxical deterioration in the bone scan appearances after 3 mo treatment was seen. This was characterized by increased activity in baseline lesions and the appearance of new foci of tracer uptake; changes which are indistinguishable from progressive disease. After 6 mo successful treatment the bone scan improved with reduced tracer uptake and no new lesions since the 3-mo scan. New lesions appearing after 6 mo indicated progressive disease. These changes are attributed to a flare in osteoblast activity induced by successful systemic therapy and confirmed by a transient rise in osteocalcin and ALP-Bl. After 1 mo of treatment 15/16 responders showed a rise in both parameters compared with only 5/23 nonresponders (p = less than 0.001). The flare response is the rule rather than the exception after successful systemic therapy for bone metastases. The appearance of new lesions or increasing activity in known lesions during the first 3 mo is as likely to herald radiological response as disease progression.
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PMID:Bone scan flare predicts successful systemic therapy for bone metastases. 326 30

Alkaline phosphatase [ALP; orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] is a ubiquitous enzyme of unknown function expressed at high levels in cells of mineralizing tissues. To study the structure, function, and expression of ALP, a full-length cDNA of rat ALP (2415 bases) was isolated from a ROS 17/2.8 osteosarcoma cell lambda gt10 cDNA library. The predicted amino acid sequence spans 524 residues and includes an N-terminal signal peptide of 17 amino acids, the phosphohydrolase active site, a rather hydrophilic backbone with five potential N-glycosylation sites, and a short hydrophobic C-terminal sequence. ALP negative CHO cells transfected with an expression vector containing the ALP coding sequences express ALP. The rat bone, liver, and kidney ALP shows remarkable 90% homology with the corresponding human enzyme, the most divergent region being the C-terminal hydrophobic domain through which the enzyme may be anchored to the plasma membrane. The rat ALP also shows 50% homology with the human placental and intestinal ALP and 25% homology with the Escherichia coli ALP. The amino acids involved in catalysis show nearly complete homology among all known ALP sequences, suggesting that these enzymes evolved from a common ancestral gene. The rat ALP cDNA pRAP 54, used as a hybridization probe in RNA blot analysis of several tissues that express ALP, revealed the presence of an ALP mRNA of approximately equal to 2500 bases. Furthermore, hybridization patterns derived from Southern blot analysis of rat chromosomal DNA offered molecular evidence that the ALP expressed in ROS 17/2.8 osteosarcoma and various rat tissues, excluding the intestine, is the product of the same single copy gene.
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PMID:Structure and expression of rat osteosarcoma (ROS 17/2.8) alkaline phosphatase: product of a single copy gene. 342 31

An isoelectric focusing technique for the separation of alkaline phosphatase isoenzymes on cellulose acetate membrane is described. Optimal conditions for isoelectric focusing were established by changing ampholine concentration and focusing conditions. Bone, liver, intestinal, and placental isoenzymes can be resolved into various sub-bands in a pH range of 4.1 to 5.2. These sub-bands were correlated with the findings of electrophoretic isoenzyme separation. The whole procedure proves very simple to perform and comparatively time saving (4 h). This procedure may help clarify the problems of ALP isoenzyme differentiation when electrophoretic patterns are unresolved.
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PMID:Isoelectric focusing on cellulose acetate membrane: a separation procedure for alkaline phosphatase isoenzymes. 343 38

Activity of alkaline phosphatase in serum (S-ALP) was characterized and compared with that of non-specific alkaline phosphatase (APase) of hard-tissue origin in the rat. The enzyme was characterized biochemically, and optimal incubation procedures were determined. S-ALP levels were determined before and after mandibular osteotomy combined with different degrees of periosteal reflections. Separation of S-ALP isoenzymes by isoelectric focusing revealed four major bands. A marked decrease of S-ALP activity was seen after osteotomy, and all isoenzymes were affected similarly. After treatment with hyperbaric oxygen, a smaller decrease in S-ALP was seen. S-ALP could be used as a marker for hard-tissue turn-over after surgical procedures.
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PMID:Changes of serum alkaline phosphatase following mandibular osteotomy in the rat. 347 93

Mouse alkaline phosphatase [ALP; orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] was partially purified from placenta. Data obtained by immunoblotting analysis suggested that the primary structure of this enzyme has a much greater homology to that of human and bovine liver ALPs than to the human placental isozyme. Therefore, a full-length cDNA encoding human liver-type ALP was used as a probe to isolate the mouse placental ALP cDNA. The cloned mouse cDNA is 2459 base pairs long and is composed of an open reading frame encoding a 524-amino acid polypeptide that contains a putative signal peptide of 17 amino acids. Homology at the amino acid level of the mouse placental ALP is 90% to the human liver isozyme but only 55% to the human placental counterpart. RNA blot hybridization results indicate that the mouse placental ALP is encoded by a gene identical to the gene expressed in mouse liver, kidney, and teratocarcinoma stem cells. This gene is therefore evolutionarily highly conserved in mouse and human.
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PMID:Cloning and characterization of a cDNA coding for mouse placental alkaline phosphatase. 347 79

Purification of human bone alkaline phosphatase, derived from human osteosarcoma tissue, has been carried to electrophoretic homogeneity. The purification procedure involved three major steps: (1) chromatography on hydroxylapatite; (2) ion exchange chromatography; and (3) gel filtration. The resultant purified enzyme is a glycoprotein, has a molecular weight of approximately 80,000 (consistent with previous reports for the bone isoenzyme), and is characteristically inhibited by modest heat (56 degrees C, 30 min) and L-homoarginine but not by L-phenylalanine. The isolation and purification procedure described can lead to the production of significant amounts of highly purified bone alkaline phosphatase. Purified ALP can be used for an analysis of minor structural differences that appear to exist between the bone, liver and kidney isoenzymes. Such information could lead to the development of a clinical diagnostic procedure specifically for bone alkaline phosphatase.
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PMID:Purification of bone alkaline phosphatase from human osteosarcoma. 350 97


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