SEARCH · PubMed Health

Results for “PYROPHOSPHATES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources

PubMed2004

Structure of 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase from Shewanella oneidensis at 1.6 A: identification of farnesyl pyrophosphate trapped in a hydrophobic cavity.

Isopentenyl pyrophosphate (IPP) is a universal building block for the ubiquitous isoprenoids that are essential to all organisms. The enzymes of the non-mevalonate pathway for IPP synthesis, which is unique to many pathogenic bacteria, have recently been explored as targets for antibiotic development. Several crystal structures of 2C-methyl-D-erythritol-2,4-cyclophosphate (MECDP) synthase, the fifth of seven enzymes involved in the non-mevalonate pathway for synthesis of IPP, have been reported; however, the composition of metal ions in the active site and the presence of a hydrophobic cavity along the non-crystallographic threefold symmetry axis has varied between the reported structures. Here, the structure of MEDCP from Shewanella oneidensis MR1 (SO3437) was determined to 1.6 A resolution in the absence of substrate. The presence of a zinc ion in the active-site cleft, tetrahedrally coordinated by two histidine side chains, an aspartic acid side chain and an ambiguous fourth ligand, was confirmed by zinc anomalous diffraction. Based on analysis of anomalous diffraction data and typical metal-to-ligand bond lengths, it was concluded that an octahedral sodium ion was 3.94 A from the zinc ion. A hydrophobic cavity was observed along the threefold non-crystallographic symmetry axis, filled by a well defined non-protein electron density that could be modeled as farnesyl pyrophosphate (FPP), a downstream product of IPP, suggesting a possible feedback mechanism for enzyme regulation. The high-resolution data clarified the FPP-binding mode compared with previously reported structures. Multiple sequence alignment indicated that the residues critical to the formation of the hydrophobic cavity and for coordinating the pyrophosphate group of FPP are present in the majority of MEDCP synthase enzymes, supporting the idea of a specialized biological function related to FPP binding in a subfamily of MEDCP synthase homologs.

Aldose-Ketose Isomerases↗

PubMed1979

The dolichol pathway of protein glycosylation in rat liver. Stimulation by GTP of the incorporation of N-acetylglucosamine in endogenous lipids and proteins of rough microsomes treated with pyrophosphate.

Incorporation of N-acetylglucosamine into endogenous lipid and protein acceptors was investigated on heavy microsomes from rat liver, incubated with UDP-N-acetyl[14C]glucosamine and GDP-mannose in the absence of detergent. This subcellular preparation derived for 95% or more from the rough endoplasmic reticulum and was devoid of Golgi components which contain the enzyme that adds the peripheral N-acetylglucosamine units to glycoproteins. The label was found almost exclusively in dolichyl diphosphate N-acetylglucosamine, except when the subcellular preparation was treated with pyrophosphate and subsequently incubated with the nucleotide sugars in the presence of GTP. Then, the incorporation of N-acetylglucosamine was considerably enhanced, and the additional label was associated with dolichyl diphosphate N,N'-diacetylchitobiose, with dolichyl diphosphate oligosaccharides and with proteins. The time-course of N-acetylglucosamine incorporation in these products was compatible with the pathway of dolichyl diphosphate glycoconjugates for the biosynthesis of the core portion of saccharide chains linked to asparagine residues of glycoproteins. The addition of GDP-mannose to the incubation medium was required to produce labeled dolichyl diphosphate oligosaccharides, but not to incorporate N-acetylglucosamine in protein. It is concluded that rough microsomes are capable of assembling dolichol-linked oligosaccharides from exogenous nucleotide precursors and of transferring N,N'-diacetylchitobiose, or its mannosylated derivatives, from the lipid intermediate to endogenous proteins. However, these metabolic activities are hindered in the original subcellular preparation, and in the absence of GTP. Although the earliest perceptible effect produced jointly by the treatment with pyrophosphate and by GTP was the synthesis of dolichyl diphosphate N,N'-diacetylchitobiose, the primary action of these factors remains uncertain. They may stimulate directly the reaction forming dolichyl diphosphate N,N'-diacetylchitobiose from dolichyl diphosphate N-acetylglucosamine, or activate the synthesis of this latter intermediate from a particular pool of dolichyl monophosphate which is readily converted afterwards into disaccharide and oligosaccharide derivatives and glycosylates protein. The requirement for GTP might have a functional meaning, for GTP acted maximally at a concentration distinctly lower than its actual concentration in liver. The detachment of ribosomes from rough vesicles was the major alteration induced by treatment with pyrophosphate. It is suggested that the removal of ribosomes unmasks the membrane sites where GTP acts.

Acetylglucosamine↗

PubMed1957

The association of blood cholinesterase levels with the susceptibility of animals to sarin and ethyl pyrophosphate poisoning.

An association between the blood cholinesterase (ChE) levels and the toxicity of sarin and ethyl pyrophosphate has been established. This has been demonstrated in two types of experiment. In the first, guinea-pigs were given a non-lethal dose of sarin (isopropyl methylphosphonofluoridate) which reduced the blood ChE to 20% of normal, and at intervals, as the ChE level of the blood gradually recovered, separate batches were given a second dose of the same size. A comparison was then made between the blood ChE levels immediately prior to the injection of the second dose and the mortality rate. In the second, a relatively small dose of sarin or ethyl pyrophosphate was given daily to rabbits until the enzyme value fell to a steady level. LD50 values were then determined on such groups and compared with those found in saline treated ones. In both guinea-pigs and rabbits it has been shown that a depression of blood ChE to below 40% indicated an increased toxicity of sarin and ethyl pyrophosphate to these species. The approximate quantitative relation appears to be that susceptibility is increased in the ratio 1.5 when the blood ChE is reduced by half.

Animals↗

PubMed1981

Increased pyrophosphate in fibroblasts and lymphoblasts from patients with hereditary diffuse articular chondrocalcinosis.

The metabolic and genetic factors leading to deposition of calcium pyrophosphate crystals in cartilage of patients with chondrocalcinosis are not well understood. Analysis of cultured fibroblasts and lymphoblasts from 12 affected members of a large kindred showed a mean concentration of intracellular inorganic pyrophosphate two times greater than that in cells from unaffected family members or normal, unrelated volunteers. Increased intracellular pyrophosphate may, therefore, be a biochemical marker for the heterozygous expression of the chondrocalcinosis gene.

Cells, Cultured↗

PubMed1982

Pyrophosphate arthropathy: a study of metabolic associations and laboratory data.

105 consecutive patients with pyrophosphate arthropathy have been studied. Disease associations and metabolic abnormalities were compared with those of an age and sex matched group of 105 acute medical admissions, and with 48 patients presenting with uncomplicated osteoarthritis. Patients with pyrophosphate arthropathy had a higher incidence of hypothyroidism (10, hyperparathyroidism 92), and chronic steroid therapy (15) than did those in the comparative groups. Laboratory data showed abnormalities suggesting chronic inflammatory disease in many patients, but no other unexpected metabolic findings. Metabolic abnormalities were uncommon in pyrophosphate arthropathy, and extensive metabolic screening of patients was unrewarding.

Adrenal Cortex Hormones↗

PubMed1980

Correlation of 99mTc-pyrophosphate myocardial accumulation with left ventricular wall motion abnormalities.

Reports have indicated that myocardial accumulation of 99mTc-pyrophosphate occurs in the absence of a recent myocardial infarction. An attempt was made to determine if myocardial accumulation, in the absence of a recent infarction, may be associated with left ventricular wall motion abnormalities. 51 patients undergoing elective left ventriculography had 99mTc-pyrophosphate cardiac scans 24-28 h prior to the procedure. 33 (33/51) patients had myocardial accumulation; all 33 had left ventrcular wall motion abnormalities. Localized myocardial accumulation occurred in 21 (21/33) patients; 19 of the 21 had localized left ventricular wall motion abnormalities corresponding to the area of myocardial accumulation. 12 (12/33) patients had diffuse myocardial accumulation; 4 had diffuse left ventricular hypokinesis and 8 had localized myocardial dysfunction. 18 (18/51) patients had no myocardial accumulation of the radionuclide; 9 had normal wall motion in all areas and 9 had localized dysfunction. The data strongly suggest that myocardial accumulation of 99mTc-pyrophosphate in the absence of a recent myocardial infarction is associated with a left ventricular wall motion abnormality.

Adult↗

PubMed1975

Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology.

Technetium-99m stannous pyrophosphate was utilized for myocardial imaging in 202 patients admitted to the hospital with chest pain of uncertain etiology. One hundred and one patients had clinical and evolved electrocardiographic and enzymatic evidence of acute myocardial infarction. Ninety-six of these 101 patients had increased myocardial uptake of the technetium stannous pyrophosphate and positive myocardial scintigrams; there was nearly precise correlation between the ECG and myocardial imaging localization of the area of infarction for acute transmural myocardial infarctions. In the five patients with negative myocardial images the scintigrams were obtained after seven or more days had elapsed following the myocardial infarction. In the remaining 101 patients no clinical, ECG, or enzymatic evidence of infarction developed; 92 of these patients had negative myocardial scintigrams. Seven of the remaining nine patients were admitted with "unstable angina pectoris", and despite the absence of diagnostic ECG and enzyme evolution each of these patients had faintly and diffusely positive myocardial scintigrams. The remaining two patients had positive myocardial scintigrams but no definite ECG or enzymatic evidence of acute myocardial infarction. Thus the technetium pyrophosphate imaging technique appears safe, inexpensive and to correlate well with ECG and enzyme identification of the presence of infarction and with ECG localization of myocardial infarction. In addition the positive myocardial scintigrams in some patients with "unstable angina" suggest that there may be limited myocardial necrosis that is ordinarily undetected by ECG and enzymes in these patients. The incidence of false positive and false negative scintigrams appears to be small.

Angina Pectoris↗

PubMed1976

Evaluation of 99mtechnetium stannous pyrophosphate as an imaging agent in acute myocardial infarction.

Serial 99mTc pyrophosphate scintigrams were obtained 7 hr to 15 days after experimental acute myocardial infarction produced by permanent or transient coronary occlusion. Scintigrams were interpreted visually and the increased radioactivity in the precordial image was quantitated and compared to extent of infarction found histologically. Results of these studies indicate: 1) 99mTc pyrophosphate imaging is an extremely sensitive for detection of acute myocardial infarction, i.e., infarction in excess of 1% of the left ventricular mass was detected. 2) Early detection of acute infarction is a function of blood flow since 7 hr after infarction scans were negative after permanent occlusion but were strongly positive after transient occlusion. 3) Radioactivity in the precordial image was inversely related to extent of infarction after permanent occlusion and directly related to extent of infarction after transient occlusion. 4) 99mTc pyrophosphate localized in areas with significant histologic infarction but the distribution of radioactivity was not proportional to extent of infarction.

Animals↗

PubMed1978

Formation of steroids by the pregnant mare. VI. Metabolism of [14C]farnesyl pyrophosphate and [3H]dehydroepiandrosterone injected into the fetus.

A mixture of [4,8,12-14C]farnesyl pyrophosphate and [3H]dehydroepiandrosterone was injected into a horse fetus im during laparotomy, after which maternal urine was collected for 6 days. Steroid conjugates in the urine were extracted with Amberlite XAD-2 resin, hydrolyzed, and separated into phenolic and neutral fractions. Estrone, 17 alpha-estradiol, equilin [3-hydroxy-1,3,5(10),7-estratetraen-17-one], and 17 alpha-dihydroequilin [1,3,4(10),7-estratetraene-3,17 alpha-diol] were isolated from the phenolic fraction and their radiochemical purities were established. Only estrone and 17 alpha-estradiol contained both 3H and 14C, while the B ring unsaturated estrogens, equilin and 17 alpha-dihydroequilin, contained only 14C. From the neutral fraction, 14C-labeled 3 beta-hydroxy-5 alpha-pregnan-20-one, 5 alpha-pregnane-3 beta-20 beta-diol, and 5 alpha-pregnane-3 beta, 20 alpha-diol were isolated. These results together with our previous findings demonstrate that the route of biosynthesis of both the ring B saturated and unsaturated estrogens is the same up to the stage of farnesyl pyrophosphate. Thus, the bifurcation in the classical pathway of steroid biosynthesis is occurring at a point after the formation of farnesyl pyrophosphate and before the formation of squalene and cholesterol.

Animals↗

PubMed1975

Extra-osseous localization of 99Tcm-Sn pyrophosphate.

99Tcm-Sn pyrophosphate bone scans of 250 patients referred for skeletal metastatic survey were analysed to determine the frequency of abnormal extra-osseous localization and the various pathological causes. Twenty-six patients demonstrated abnormal extra-osseous concentration. There were three false positives. Sixty-five per cent of the extra-osseous lesions concentrating pyrophosphate were malignant (carcinoma of lung and breast, metastatic hepatic carcinoma, chondrosarcoma) and the remainder were benign lesions, e.g. sarcoidosis, soft-tissue calcification, post-surgical and irradiation sites. An incidental finding was the unusual frequency of accumulation of pyrophosphate in various joints, especially the knees and shoulders in asymptomatic patients above 70 years of age.

Age Factors↗

PubMedDate not supplied

Calcium gradient dependent pyrophosphate formation by sarcoplasmic vesicles.

The vesicles of the sarcoplasmic membranes synthesize pyrophosphate from inorganic phosphate. Pyrophosphate synthesis proceeds as long as a calcium gradient is maintained across the vesicular membranes. Pyrophosphate synthesis is inhibited by low concentrations of nucleoside triphosphates.

Adenine Nucleotides↗

PubMed2006

Recognition of ribonuclease A by 3'-5'-pyrophosphate-linked dinucleotide inhibitors: a molecular dynamics/continuum electrostatics analysis.

The proteins of the pancreatic ribonuclease A (RNase A) family catalyze the cleavage of the RNA polymer chain. The development of RNase inhibitors is of significant interest, as some of these compounds may have a therapeutic effect in pathological conditions associated with these proteins. The most potent low molecular weight inhibitor of RNase reported to date is the compound 5'-phospho-2'-deoxyuridine-3-pyrophosphate (P-->5)-adenosine-3-phosphate (pdUppA-3'-p). The 3',5'-pyrophosphate group of this compound increases its affinity and introduces structural features which seem to be unique in pyrophosphate-containing ligands bound to RNase A, such as the adoption of a syn conformation by the adenosine base at RNase subsite B(2) and the placement of the 5'-beta-phosphate of the adenylate (instead of the alpha-phosphate) at subsite P(1) where the phosphodiester bond cleavage occurs. In this work, we study by multi-ns molecular dynamics simulations the structural properties of RNase A complexes with the ligand pdUppA-3'-p and the related weaker inhibitor dUppA, which lacks the 3' and 5' terminal phosphate groups of pdUppA-3'-p. The simulations show that the adenylate 5'-beta-phosphate binding position and the adenosine syn orientation constitute robust structural features in both complexes, stabilized by persistent interactions with specific active-site residues of subsites P(1) and B(2). The simulation structures are used in conjunction with a continuum-electrostatics (Poisson-Boltzmann) model, to evaluate the relative binding affinity of the two complexes. The computed relative affinity of pdUppA-3'-p varies between -7.9 kcal/mol and -2.8 kcal/mol for a range of protein/ligand dielectric constants (epsilon(p)) 2-20, in good agreement with the experimental value (-3.6 kcal/mol); the agreement becomes exact with epsilon(p) = 8. The success of the continuum-electrostatics model suggests that the differences in affinity of the two ligands originate mainly from electrostatic interactions. A residue decomposition of the electrostatic free energies shows that the terminal phosphate groups of pdUppA-3'-p make increased interactions with residues Lys(7) and Lys(66) of the more remote sites P(2) and P(0), and His(119) of site P(1).

Adenosine Monophosphate↗

PubMed2003

Enzymatic determination of pyrophosphate in urine by flow methods.

Two flow methods for the enzymatic determination of pyrophosphate are described that are used to diminish the consumption of reagents. One method is based on the use of an open-close circuit with manual injection using a syringe. The other is a sequential injection method. The analytical features of both methods are: a linear range of 0.4 - 20 mg L(-1), an LOD of 0.38 mg L(-1), and a CV of 2.0% for the sequential injection method, and a linear range of 0.3 - 15 mg L(-1), an LOD of 0.29 mg L(-1), and CV of 2.2% for the open-close circuit method. The methods were applied to the determination of pyrophosphate in urine. The pyrophosphate concentration determined in urine samples varied from 1.26 to 6.67 mg L(-1).

Diphosphates↗

PubMed1993

Effect of an anticalculus toothpaste containing pyrophosphate on pyrophosphatase activity and the state of calcium phosphate in saliva.

Experiments were performed to determine if a pyrophosphate-containing anticalculus toothpaste could affect certain salivary constituents involved in the mineralization of dental plaque. The findings indicated no obvious changes in acid and alkaline pyrophosphatases, ionized calcium, total calcium, inorganic phosphate or pH in saliva for 1-135 min after brushing the teeth with the anticalculus toothpaste. Data obtained by brushing with the toothpaste three times daily for two weeks also confirmed these results. Our findings clearly indicate that pyrophosphate-stabilizing agents in the anticalculus toothpaste are not fully effective in the oral cavity. In addition, the pyrophosphate-containing toothpaste has no influence on the state of calcium and phosphate in saliva.

Adult↗

PubMed1996

Periodontoid calcium pyrophosphate dihydrate deposition disease: "pseudogout" mass lesions of the craniocervical junction.

Between 1984 and 1996, seven patients with symptomatic masses located posterior to the odontoid process and containing calcium pyrophosphate dihydrate crystals were evaluated by the senior author (A.H.M). All patients presented with distal paresthesias and myelopathy and underwent transoral-transpharyngeal resection of the anterior arch of C-I, the odontoid process, and the compressing mass. Histological examination revealed the characteristic changes of calcium pyrophosphate dihydrate (CPPD) deposition disease, with nodular deposits of birefringent rhomboid crystals. On magnetic resonance imaging, the masses appeared predominantly isointense with neural tissue on T1-weighted images and iso-to hyperintense on T2-weighted images. On computerized tomography scans, small area of calcifications within the masses were apparent in all cases. All patients improved postoperatively, with six of seven patients requiring posterior fixation for instability as a second procedure. Calcium pyrophosphate dihydrate deposition causing periodontoid mass lesions is a distinct clinical disease entity that probably is underdiagnosed. In the authors' l opinion, the diagnosis can often be established preoperatively by the distinctive neuroradiological appearance of the masses. Therefore, CPPD deposition disease should be considered in the differential diagnosis of masses of the craniocervical junction, because it is amenable to early surgical intervention. The consulting neuropathologist should be made aware of this diagnostic possibility at the time of surgery.

Aged↗

PubMed1976

[Diagnosis of cerebrovascular disorders using stannous technetium pyrophosphate].

A total of 122 cases of various neurological diagnoses (among which 72 cerebral infarcts, 7 intracerebral hematomas and 38 intracranial tumors) had two separate brain scans, performed within 48 hours of each other after the administration of pertechnetate and technetium stannous pyrophosphate. The comparison of the resulting seans indicates that, in addition of an osseous accumulation, the pyrophosphate localizes greatly in ischemic cerebral lesions, especially those observed during the second week of evolution. It seems that the uptake of pyrophosphate reflects the area of anaerobic changes whereas the accumulation of pertechnetate depends on the disruption of the blood brain barrier. The scintigraphic diagnostic of cerebral infarctions is greatly improved.

Brain Neoplasms↗

PubMed1998

Evaluation of a dental floss containing soluble pyrophosphate on calculus formation using a short-term clinical model.

This clinical study compared the effect of a dental floss containing 0.25 mg tetrasodium pyrophosphate per cm and a placebo floss on supragingival calculus formation using a 6-week, partial-mouth toothshield model. The six lower anterior teeth were scaled and polished before each 2-week period (i.e., pre-trial, washout, trial). During both the pre-trial and trial periods, subjects brushed twice daily with a non-tartar control dentifrice, while a toothshield protected the six test teeth from brushing. After rinsing with water and removing the shield, they flossed the test teeth. All subjects used placebo floss during the pre-trial period in order to determine the baseline Volpe-Manhold Index (VMI) calculus formation scores, which were used to balance groups for the trial period. During the trial period, one group used the placebo floss, while the second group used the pyrophosphate floss. The final results demonstrated that the pyrophosphate floss significantly inhibited calculus formation between teeth (mesial-distal scores) by 21%, and on labial surfaces by 37% relative to the placebo floss.

Adult↗

PubMed1975

[Bone scintigraphy with 99m Tc pyrophosphate in neurology].

99MTc pyrophosphate has restored bone scintigraphy to the position of respectability it had lost with radiostrontium 85 and 87m, and it has rapidly become the method of choice for the detection of osteogenic hyperactivity. In cases of tumor the histologic disorder is frequently detected prior to the morphologic changes seen in X-ray pictures. The biophysical properties of 99mTc pyrophosphate provide high quality imaging of the skeleton. The scans or scintiphotos render possible a more sensitive and earlier diagnosis than radiography, though bone scanning does not of course supersede radiography. The two methods are complementary. In present day oncologic practice, however, bone scintigraphy with 99mTc pyrophosphate replaces to advantage the conventional radiographic "bone survey". In neurology the change is already appreciable and has proved its worth. In the light of results in 78 neurologic patients attention is drawn to the significant changes bone scintigraphy has brought about in diagnosis and therapeutic planning. The indications which have already emerged from this new method of nuclear neurology are tabulated, discussed and illustrated.

Adult↗