Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We used heat inactivation, L-phenylalanine inhibition, and electrophoresis on polyacrylamide gel and cellulose acetate membranes--with and without use of specific antisera against the liver-bone, intestinal, and placental isoenzymes--to distinguish and quantitate the different alkaline phosphatase isoenzymes in sera from 23 adult members of a kindred affected by the adult form of hypophosphatasia. Nine subjects had values for total activity more than two standard deviations below the mean values for age- and sex-matched normal persons. Bone isoenzyme was diminished in all nine, whereas liver isoenzyme was subnormal in only four. Phosphoethanolamine and phosphoserine in the urine of eight hypophosphatasemic individuals correlated inversely with both total and liver alkaline phosphatase activity in their serum, but not with the activity of the bone isoenzyme. Total activity in the serum of adult kindred members correlated best with the circulating liver isoenzyme activity. The findings suggest that altered hepatic metabolism is responsible for the increased urinary excretion of phosphoethanolamine, and perhaps phosphoserine, in hypophosphatasia.
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PMID:Hypophosphatasia (adult form): quantitation of serum alkaline phosphatase isoenzyme activity in a large kindred. 737 6

Two siblings with hypophosphatasia, one of whom was autopsied, were reported. The first case which was a product of a 26-year-old mother complicated by hydroamnios represented poor mineralization of the entire bones on X-ray examination and died shortly after birth. The second case weighing 1850 g delivered from the same mother had a rhizomelic micromelia and poor visualization of the skull, long bones and vertebral bones on X-ray at postmortem. The autopsy on the second case showed small thoracic cage with rachitic rosaries of ribs, membranous skull and poorly ossified vertebral and long bones. Microscopically, there was a marked disturbance of both enchondral and membranous ossifications similar to the histology of rachitis. A biochemical examination showed low alkaline phosphatase, high calcium and normal PTH in the serum. Further examination of their family revealed relatively low level of alkaline phosphatase of the parents and one of their brothers which suggsted they were carriers of hypophosphastasia. Previous reports on hypophosphatasia were reviewed and differential diagnosis of hypophosphatasia from the other congenital dwarfisms was discussed.
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PMID:Two siblings with hypophosphatasia. 741 41

Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.
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PMID:Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy. 770 47

The causes for low serum alkaline phosphatase (ALP) activity (reference range 30-115 U/L) in a large Veterans Medical Center were reviewed. Of 69,864 ALP determinations made over a 4-year period, 130 were low (< 30 U/L, 0.19%), representing 88 individual patients. Of these, 83 (primarily men, 96%) patients' charts were reviewed and classified into two groups, those with and those without conditions previously reported to be associated with decreased serum ALP activity: 47% had conditions associated with low ALP activity, the most frequent being cardiac surgery and cardiopulmonary bypass (26.5%), malnutrition (12.0%), magnesium deficiency (4.8%), hypothyroidism (2.4%), and severe anemia (1.2%); 53% of patients did not have clinical conditions previously associated with low ALP activity. No case of clinically apparent hypophosphatasia, for which low ALP activity is the defining characteristic, was found in this population of veterans. A low serum ALP may be of significance in other patient populations such as children, where it is associated with achondroplasia and cretinism, or in postmenopausal women with osteoporosis taking estrogen replacement therapy. In the predominantly adult male population in this study, low ALP activity was rare; it was seen most frequently in cardiac surgery patients postoperatively, a clinical condition heretofore not commonly associated with low serum ALP activity.
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PMID:Significance of low serum alkaline phosphatase activity in a predominantly adult male population. 772 Feb 39

Infantile type hypophosphatasia, an autosomal recessive disease with severe clinical manifestations, is characterized biochemically by subnormal activities of circulating alkaline phosphatase. In this report, we presented a five-day-old male with this rare disorder. His parents were first cousins, and he was first seen for jaundice. He had soft calvaria, large fontanel, extremely wide cranial sutures, low-set ears, a depressed nasal bridge, funnel chest, and short and bowed distal limbs. Roentgenographic studies showed widened sutures and poor ossification of the skull, bowing of the femora and slight modeling defects in the long bones. A low serum alkaline phosphatase activity led us to measure excretion of phosphoethanolamine and found it to be increased.
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PMID:Hypophosphatasia in a newborn infant. 773 10

Hereditary hypophosphatasia and hyperphosphatasia are two rare skeletal disorders, which commonly present during childhood and are characterized by a decrease and an increase, respectively, in serum tissue nonspecific alkaline phosphatase activity. The primary defect in hereditary hypophosphatasia appears to be a structural abnormality in the tissue nonspecific alkaline phosphatase gene, resulting in a decrease or absence of enzymatic activity. The pathogenesis of hyperphosphatasia is unknown. There is no treatment for hypophosphatasia. Treatment with pamidronate appears promising for patients with hereditary hyperphosphatasia.
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PMID:Hereditary hypophosphatasia and hyperphosphatasia. 806 Jul 71

Alkaline phosphatase is an enzyme present in nearly all living organisms. The liver/bone/kidney-type isozyme (ALPL) is expressed in the liver, bone, kidney and in most other tissues. We have isolated the ALPL cDNA and its gene and indicated that the gene is divided into two leader exons (exon 1B and 1L) and 11 coding exons and the liver- and bone-specific transcriptions are regulated by their own promoters. The defect of ALPL results in infantile hypophosphatasia, a disorder characterized by defective bone mineralization and subnormal activity of circulating alkaline phosphatase. Prenatal diagnoses of the disease were successfully carried out. Mutation analysis of the family member is in progress.
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PMID:[Molecular cloning of liver/bone/kidney-type alkaline phosphatase complementary and genomic DNA: analyses of its deficiency, infantile hypophosphatasia]. 809 53

A major impasse to understanding the physiologic role(s) of alkaline phosphatase (ALP) is uncertainty as to its natural substrates. Various in vitro studies have led other investigators to suggest that ALP functions as a plasma membrane phosphoprotein phosphatase, consistent with our demonstration of ecto-topography of ALP in a variety of cell types. Thus, we compared the phosphorylation of plasma membrane proteins from control fibroblasts to those from profoundly ALP-deficient fibroblasts of hypophosphatasia patients. Fibroblasts from 3 controls and 3 hypophosphatasia patients (ALP activity < 4% of control) were biosynthetically labeled with 32Pi for 2 h. 32P incorporation into total trichloroacetic acid (TCA)-precipitable material was not significantly different in control and patient cells. Plasma membranes were prepared from these cells by hypotonic shock, solubilized, and subjected to two-dimensional (2-D) gel electrophoretic separation. Video densitometric analysis of silver-stained 2-D gels failed to reveal any consistent difference in the protein profile between patient vs. control fibroblasts (i.e., unique species, altered pls, or increased abundance). Autoradiography of individual 2-D gels demonstrated 63 plasma membrane phosphoproteins with molecular weights ranging from 15 to 152 kDa and predominantly acidic pls. Although several of these phosphoproteins appeared to have had donor-specific labeling, none was unique or especially abundant in the hypophosphatasia group. Thus, in ALP-deficient fibroblasts, normal incorporation of 32P into total cellular protein and into all identifiable plasma membrane phosphoproteins indicates that ALP does not modulate the phosphorylation of plasma membrane proteins.
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PMID:Evidence against a role for alkaline phosphatase in the dephosphorylation of plasma membrane proteins: hypophosphatasia fibroblast study. 822 82

Hypophosphatasia is rare enzymopathy that normally presents within the first few years of life and often has profound effects upon the periodontium. It is a heritable disorder characterised by defective mineralisation of the skeletal and dental structures of the body and a deficiency in the liver/bone/kidney (L/B/K) isoenzyme of alkaline phosphatase (ALP). There has been a tremendous advance in our knowledge of this condition over the last decade due to the advent of highly specific DNA probes and novel microanalytical techniques. This paper aims to review current literature about hypophosphatasia with special reference to the dental aspects of the condition and to shed light upon the controversial area of its mode of genetic inheritance. It is concluded that hypophosphatasia may result from the existence of 2 defective alleles, which alone or in combination may cause the condition. One allele is expressed in an autosomal dominant manner producing milder phenotypic characteristics, whilst the other is expressed in an autosomal recessive manner producing the more severe clinical form that often results in neonatal death. The milder phenotypes may go undiagnosed and the consequence of this in genetic counselling terms is extremely important.
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PMID:Hypophosphatasia: dental aspects and mode of inheritance. 822 47

Hypophosphatasia is a congenital disease characterized by defective bone mineralization, deficiency of alkaline phosphatase (ALP) activity, increased excretion of the phosphoethanolamine (PEA) in the urine, and premature loss of the deciduous teeth. A male hypophosphatasia patient (aged 15 years 6 months) with premature exfoliation of the deciduous teeth was referred to our hospital because of severe periodontal destruction in the permanent dentition. Blood and urine tests as well as oral and periodontal examinations were performed. Serum antibody titers against 7 periodontopathic bacteria by the enzyme-linked immunosorbent assay (ELISA), monocyte and neutrophil chemotaxis measurements, and cellular immunity tests were also performed. Low levels of ALP in serum and PEA in the urine were found. Monocyte and neutrophil chemotaxis exhibited normal values. Slightly depressed CD2+, CD3+, and CD4+ and slightly elevated activity of NK cells were found. An elevated level of serum antibody to Porphyromonas gingivalis was observed. Oral radiographic examination showed a mirror pattern of alveolar bone loss which is similar to that seen in localized juvenile periodontitis. Periodontal treatment of this patient was carried out for 4 years. The severely affected sites, the lower right and left first molars and the upper right first molar, had to be extracted. However, the other sites were well maintained. The serum IgG level against P. gingivalis was decreased after 4 years of periodontal treatment. Infection with P. gingivalis was suspected to be associated with the destruction of this patient's hypophosphatasia, but other dental abnormalities such as abnormal enamel, dentin, and cementum formation may also have contributed to the periodontal pathology.
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PMID:Clinical and laboratory studies of severe periodontal disease in an adolescent associated with hypophosphatasia. A case report. 838 14


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