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

Among the noninvasive methods proposed for the study of collagen metabolism as an of fibrosis and inflammation, the most widely accepted method is quantitation in serum of the N-terminal peptide of type III procollagen (P-III-Ps). We measured this variable in 87 subjects classified into five study groups: 19 controls (C), 18 alcoholics (E), 15 patients diagnosed as liver cirrhosis (CH), 11 chronic liver disease (HC) and 24 pregnant women (EMB). In our environment, the serum level of P-III-P in the healthy population was 9.12-12.8 ng/ml. In 27.77% of the alcoholics studied (5 cases) the mean value exceeded this level, 19.35 +/- 3.05 ng/ml. Forty percent of the cirrhotics (6 cases) presented the highest values, 26.54 +/- 11.45 ng/ml, while 83.33% of the patients with chronic active hepatitis presented a mean value of 18.53 +/- 3.8 ng/ml. Of the 24 pregnant women, 95.83% (23 cases) had higher than normal values, and concentrations roses in the last trimester of gestation with respect to the previous trimesters. Analysis of the correlations of all the biochemical parameters of liver function with P-III-Ps disclosed a relationship between P-III-Ps and alkaline phosphatase in the groups of cirrhotics and chronic persistent hepatitis (p less than 0.05). We conclude that the N-terminal peptide of type III procollagen is a useful marker of active fibrosis.
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PMID:[Serum determination of N-terminal peptide of type III procollagen as a marker of fibrotic activity]. 273 69

Mammalian cells contain two subspecies of RNA polymerase II, designated IIO and IIA. The objectives of these studies were to determine the structural relationship between these subspecies and to determine the functional significance of these differences. Subunits IIo and IIa were purified from calf thymus, and the effect of alkaline phosphatase treatment on electrophoretic mobility and immunochemical reactivity was examined. The removal of phosphate converts subunit IIo to a form indistinguishable from that of subunit IIa. These results indicate that subunit IIo is produced by multisite phosphorylation of subunit IIa. The distribution of phosphate within subunit IIo was determined by CNBr cleavage of in vivo labeled HeLa cell RNA polymerase II. 32P-Labeled subunit IIo was purified by immunoprecipitation and cleaved with CNBr, and the resultant peptides were analyzed. The quantitative recovery of 32P in the C-terminal peptide establishes that this domain is the primary site of phosphorylation. In an effort to assess the level of phosphorylation of the transcriptionally active form of RNA polymerase II in HeLa nuclei, transcription was carried out in the presence of 4-thiouracil triphosphate and the nascent labeled transcript cross-linked to RNA polymerase. Specific photoaffinity labeling of subunit IIo was observed. Alkaline phosphatase treatment results in an increase in the mobility of photoaffinity labeled subunit IIo to approach that of subunit IIa. These results indicate that subunit IIo is a component of transcriptionally active RNA polymerase II.
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PMID:Messenger RNA synthesis in mammalian cells is catalyzed by the phosphorylated form of RNA polymerase II. 362 68

The gamma-carboxy glutamic acid (Gla)-containing protein of mammalian bone (BGP, also called osteocalcin) is a 49 amino acid polypeptide containing two to three residues of gamma-carboxyglutamic acid. BGP is synthesized by osteoblastlike cells, and plasma BGP in laboratory animals is derived principally from recently synthesized BGP. These data, taken together with observations that plasma BGP levels are elevated in patients with disorders of high bone turnover, suggest that plasma BGP is a marker of osteoblast activity. Since low bone formation rates may play an important role in the loss of bone mass with age, we have examined the determinants of plasma BGP levels in aging subjects, using a region-specific radioimmunoassay for human BGP based on the synthetic C-terminal peptide hBGP37-49. In 147 carefully screened healthy subjects, aged 23-91, BGP did not change with age, whereas alkaline phosphatase (AP) showed a significant positive correlation (r = 0.30, P less than 0.001). Creatinine clearance (GFR) declined by 0.9 ml/min/yr and correlated with both BGP (r = -0.21, P less than 0.001) and AP (r = -0.21, P less than 0.001). However, correlation of AP with age persisted after controlling for GFR. BGP was not correlated with serum PTH, urine Ca/GFR, or urine cAMP/GFR. In 48 patients with known parenchymal renal disease studied for comparison, plasma BGP was increased at a serum creatinine of greater than or equal to 1.8 mg/dl. Our results indicate that plasma BGP, a specific marker of bone metabolism, is not predictably related to age per se. This result is in contrast to the age-related rise in total AP. Subtle changes in renal function can affect plasma BGP levels.
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PMID:Determinants of bone gamma-carboxyglutamic acid-containing protein in plasma of healthy aging subjects. 387 50

Limited proteolysis of rabbit skeletal muscle AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) with trypsin results in conversion of the enzyme to a form which is no longer inhibited by ATP and exhibits hyperbolic kinetics even at low K+ concentration and in the absence of ADP. The interaction with troponin T from white skeletal muscle or with the phosphorylated 42-residue N-terminal peptide of troponin T restores in the trypsin-treated AMP deaminase the sensitivity to adenine nucleotides and increases the KA for K+ activation of the enzyme from 1 mM to 12 mM, this effect being diametrically opposite to that exerted by limited proteolysis on the native enzyme. Treatment of the N-terminal peptide of troponin T with alkaline phosphatase abolishes the modulating properties of the peptide, suggesting that phosphorylation-dephosphorylation processes may be involved in the regulation of the enzyme.
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PMID:Interaction with troponin T from white skeletal muscle restores in white skeletal muscle AMP deaminase those allosteric properties removed by limited proteolysis. 396 31

Aluminium is involved in the etiology of several complications of chronic renal failure and has been firmly established as having toxic effects on bone tissue. We have measured plasma aluminium together with serum osteocalcin, procollagen I C-terminal peptide and total alkaline phosphatase activity in healthy subjects and in a group of subjects who consumed aluminium-containing and non-aluminium containing antacid preparations, with normal renal function. Age-related healthy reference ranges for plasma aluminium are presented and the effects of chronic antacid consumption on plasma aluminium and biochemical markers of bone formation investigated. In 172 healthy subjects the mean plasma aluminium concentration was 4.4 +/- 2.9 micrograms L-1, men having a significantly greater circulating aluminium load than women (5.4 +/- 2.8 micrograms L-1 vs. 4.0 +/- 2.8 micrograms L-1 respectively (P = 0.0039)). Older men were found to have significantly higher plasma aluminium levels than younger men. Increased plasma aluminium was seen in subjects taking antacids although this was not associated with significant changes in most indices of bone formation.
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PMID:Plasma aluminium in a reference population: the effects of antacid consumption and its influence on biochemical indices of bone formation. 824 26

The purine/cytosine permease, encoded by the FCY2 gene, is a carrier located in the plasma membrane of the yeast Saccharomyces cerevisiae. Polyclonal antibodies were raised against two peptides that corresponded to the sub-N-terminal and C-terminal sequences of the putative protein deduced from the FCY2 gene. Immunoprecipitation experiments performed with protein extracts labelled in vivo with 35S showed that purine/cytosine permease is specifically detected as a broad and diffuse band. The apparent molecular mass of this protein was 45-50 kDa. By means of in vivo pulse/chase 35S-labelling experiments, we observed a slight increase in the apparent molecular mass of purine/cytosine permease during the chase. This shift in electrophoretic mobility of the protein suggested a post-translational modification. This molecular mass increase was eliminated by alkaline phosphatase treatment of the immunoprecipitate, which strongly suggested phosphorylation of the carrier. This proposal was confirmed by in vivo [32P]P(i) labelling and immunoprecipitation of purine/cytosine permease with purified anti-(sub-N-terminal peptide) IgG or anti-(C-terminal peptide) IgG. Phosphoamino acid analysis indicated that phosphorylation occurred on seryl residues of purine/cytosine permease. By means of thermosensitive secretory-pathway-mutant strains, we demonstrated that purine/cytosine permease phosphorylation occurred either between the Golgi apparatus and the plasma membrane or in the plasma membrane itself.
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PMID:In vivo phosphorylation of the purine/cytosine permease from the plasma membrane of the yeast Saccharomyces cerevisiae. 870 52

Increased levels of lipocortins occur in the nervous system in multiple sclerosis, in experimental autoimmune encephalomyelitis and experimental neuritis at the height of disease and decrease thereafter, suggesting their potential involvement in recovery from disease. We therefore investigated whether lipocortins may suppress activation of autoimmune T cells. Antigen-specific and growth factor-mediated proliferation of T cell lines reactive with myelin basic protein (MBP) was measured in the presence of recombinant lipocortin-1, -2, and -5, and natural bovine lipocortin-1 using various concentrations and incubation periods. We also employed an N-terminal lipocortin-1 peptide spanning aa 1-26, a proteolytic fragment of lipocortin-1 where the respective N-terminal region was clipped off, tested blocking with a neutralizing antibody, and investigated the effect of alkaline phosphatase treatment. Both human recombinant and bovine lipocortin-1 had a marked suppressive effect on T cell activation by MBP and the respective immunogenic peptide. When added at 3 micrograms/ml we observed up to 90% inhibition of T cell proliferation between day 2 and 3, but not at earlier time points of activation. The inhibitory effect of human lipocortin-1 was blocked after addition of a neutralizing antibody directed against lipocortin-1. Lipocortin-2 and -5, and the N-terminal peptide of lipocortin-1 were ineffective, whereas the fragment spanning residues 27-345 of lipocortin-1 retained full activity. Treatment of bovine lipocortin-1 with alkaline phosphatase did not alter immunosuppressive properties.
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PMID:Lipocortin-1 (annexin-1) suppresses activation of autoimmune T cell lines in the Lewis rat. 882 88

Enhanced bone resorption is a characteristic finding in multiple myeloma (MM). The aim of this study was to assess the newer biochemical bone markers in patients with myeloma. We studied 17 MM patients--10 males (3 untreated, 5 in remission, 2 responding), 7 females (3 in remission, 4 responding) and 15 normal controls. Serum bone specific alkaline phosphatase (BSALP), osteocalcin (OC) and procollagen type 1 C-terminal peptide (PICP) were determined as markers of bone formation, while serum tartrate resistant acid phosphatase (TRAP), urinary deoxypyridinoline (Dpyr) and calcium (Ca) were determined as markers of bone resorption and the ratio of the levels of bone formation/resorption were determined. All markers were measured by enzyme immunoassays (Metra Biosystems), except for TRAP by an in-house enzymatic assay and Ca by the cresolphthalein method. The Dpyr and Ca were expressed as a ratio to urinary creatinine (Cr) excretion. There were significantly higher (i) (Dpyr/Cr)/PICP ratio in male MM patients than in controls (P < 0.05); (ii) (a) urinary Dpyr excretion (P < 0.001), (b) (Dpyr/Cr)/BSALP ratio (P < 0.0001) and (c) (Dpyr/Cr)/PICP (P < 0.0001) in the untreated male MM subgroup than controls; (iii) (Dpyr/Cr)/BSALP ratio (P < 0.05) in the untreated than in the responding male MM subgroup, (iv) (Dpyr/Cr)/PICP ratio (P < 0.05) in untreated male patients than in those in the remission subgroup. In conclusion, (a) Dpyr is a sensitive marker in assessment of bone resorption in MM patients; (b) (Dpyr/Cr)/BSALP or (Dpyr/Cr)/PICP ratio is even more sensitive in distinguishing the untreated from the other MM subgroups and controls. Therefore, the use of a combination of these markers may have a potential role in the management of patients with MM.
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PMID:Biochemical bone markers in patients with multiple myeloma. 887 39

Previous reports have suggested the involvement of voltage-activated calcium (Ca2+) channels in bone metabolism and in particular on the secretion of osteocalcin by osteoblast-like cells. We now report that potassium (K+) channels can also modulate the secretion of osteocalcin by MG-63 cells, a human osteosarcoma cell line. When 1,25-dihydroxyvitamin D3(1,25(OH)2D3)-treated MG-63 cells were depolarized by step increases of the extracellular K+ concentration ([K+]out) from 5-30 mM, osteocalcin (OC) secretion increased from a control value of 218 +/- 13 to 369 +/- 18 ng/mg of protein/48 h (p < 0.005 by analysis of variance). In contrast, in the absence of 1,25(OH)2D3, there is no osteocalcin secretion nor any effect of cell depolarization on this activity. The depolarization-induced increase in 1,25(OH)2D3-dependent osteocalcin secretion was totally inhibited in the presence of 10 microM Nitrendipine (a Ca2+ channel blocker, p < 0.005) without affecting cellular alkaline phosphatase nor cell growth. Charybdotoxin, a selective blocker of Ca2+-dependent K+ channels (maxi-K) present in MG-63 cells, stimulated 1,25(OH)2D3-induced osteocalcin synthesis about 2-fold (p < 0.005) after either 30, 60, or 120 minutes of treatment. However, Charybdotoxin was without effect on basal release of osteocalcin in the absence of 1,25(OH)2D3 pretreatment. Using patch clamp technique, we occasionally observed the presence of a small conductance K+ channel, compatible with an ATP-dependent K+ channel (GK[ATP]) in nonstimulated cells, whereas multiple channel openings were observed when cells were treated with Diazoxide, a sulfonamide derivative which opens GK(ATP). Western blot analysis revealed the presence of the N-terminal peptide of GK(ATP) in MG-63 cells, and its expression was regulated with the proliferation rate of these cells, maximal detection by Western blots being observed during the logarithmic phase of the cycle. Glipizide and Glybenclamide, selective sulfonylureas which can block GK(ATP), dose-dependently enhanced 1,25(OH)2D3-induced OC secretion (p < 0.005). Reducing the extracellular calcium concentration with EGTA (microM range) totally inhibited the effect of Glipizide and Glybenclamide on osteocalcin secretion (p < 0.005), which remained at the same levels as controls. Diazoxide totally prevented the effect of these sulfonylureas. These results suggest that voltage-activated Ca2+ channels triggered via cell depolarization can enhance 1,25(OH)2D3-induced OC release by MG-63 cells. In addition, OC secretion is increased by blocking two types of K+ channels: maxi-K channels, which normally hyperpolarize cells and close Ca2+ channels, and GK(ATP) channels. The role of these channels is closely linked to the extracellular Ca2+ concentration.
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PMID:Pharmacological and biochemical evidence for the regulation of osteocalcin secretion by potassium channels in human osteoblast-like MG-63 cells. 942 Dec 31

In this cross-sectional study, we evaluated 15 premenopausal women to elucidate whether bone turnover is increased and bone mineral density is reduced due to endogenous subclinical hyperthyroidism. Each patient had normal free thyroxine (FT4) and free triiodothyronine (FT3) levels associated with a stable suppression (<0.1 mU/L) of serum thyrotropin (TSH) levels during a period ranging between 6 and 11 months. Metabolic parameters of bone turnover (serum osteocalcin, bone specific alkaline phosphatase, procollagen I C-terminal peptide reflecting bone formation; urinary deoxypyridinoline and calcium excretion reflecting bone resorption) were assessed. Bone mineral density was measured at lumbar 1-4 vertebrae, femoral neck, and the forearm (midshaft radius and distal radius) by dual energy x-ray absorptiometry. All measurements were compared with 15 healthy age-, height-, and weight-matched premenopausal women who served as control group. Our findings suggest that endogenous subclinical hyperthyroidism is not associated with increased bone turnover, and bone mineral density is not reduced in premenopausal women, at least in the short term.
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PMID:Effect of endogenous subclinical hyperthyroidism on bone metabolism and bone mineral density in premenopausal women. 1041 Nov 15


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