Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PYROPHOSPHATES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,423 records · Page 79Linked to original sources
PubMed2003

Mortalin-MPD (mevalonate pyrophosphate decarboxylase) interactions and their role in control of cellular proliferation.

Mortalin (mot-2/GRP75/PBP74/mthsp70) is a member of the hsp70 family of proteins and is differentially distributed in normal and immortal cells. It was shown to be involved in pathways to cell senescence and immortalization. To elucidate its functional aspects, a yeast interactive screen for mortalin (mot-2) binding proteins was performed. Mevalonate pyrophosphate decarboxylase (MPD) was identified as one of the mortalin binding partners. The interactions were confirmed in mammalian cells by two-hybrid assay and in vivo coimmunoprecipitation. MPD is known to furnish prenyl groups required for prenylation, protein modification that is essential for the activity of many proteins including p21(Ras) (Ras). We have examined the effect of MPD-mot-2 interactions on the level and activity of p21(Ras) and its downstream effectors, p44 and p42 MAP kinases (ERK1/ERK2), in Ras-Raf pathway. An overexpression of mot-2 resulted in reduced level of Ras and phosphorylated ERK2. These were rescued by co-expression of MPD from an exogenous promoter demonstrating a functional link between mot-2, MPD, and Ras. Ras and its oncogenic forms act as key players in controlling proliferation of normal and cancerous cells. Assigning mot-2 upstream of p21(Ras) offers an important mechanism for influence over cell proliferation.

Animals↗
PubMed1983

Pyrophosphate may be involved in regulation of bacterial glycogen synthesis.

Inorganic pyrophosphate is a potent inhibitor of the enzyme that catalyzes synthesis of the glucosyl donor for Escherichia coli glycogen synthesis, ADP-glucose pyrophosphorylase. The Ki is determined to be 40 microM and the substrate ATP, the activator, fructose 1,6-P2 or the allosteric inhibitor, AMP do not greatly affect the inhibition. PPi exhibits mixed type inhibition with the other substrate, glucose 1-P. The potential regulation of glycogen synthesis by PPi is discussed.

Adenosine Diphosphate Glucose↗
PubMed1985

Characterization of pyrophosphate exchange by the reconstituted adenine nucleotide translocator from mitochondria.

The transport of inorganic pyrophosphate (PPi) by the adenine nucleotide translocator from beef heart mitochondria was studied in a reconstituted system. The transport of PPi is dependent on appropriate transmembrane substrates. The activity of PPi exchange is about one tenth as compared to the ADP/ATP exchange, whereas the transport affinity for PPi is very low (2-5 mM). The adenine nucleotide carrier catalyzes a strict counterexchange of PPi and nucleotides with an exchange stoichiometry close to 1. The inhibitor specificity of PPi exchange is comparable to that of ADP/ATP exchange.

Adenosine Triphosphate↗
PubMed1987

Guanine nucleotide and pyrophosphate activate exogenous phosphatidylinositol 4,5-bisphosphate hydrolysis in rat liver plasma membranes.

5'-guanylylimidodiphosphate (GppNHp) in the presence of deoxycholate, stimulated the phospholipase C-mediated hydrolysis of exogenous [3H]phosphatidylinositol 4,5-bisphosphate ([3H]PIP2) to myo-[3H]inositol 1,4,5-trisphosphate in rat liver plasma membranes. Activation was not specific for guanine nucleotides as 5'-adenylylimidodiphosphate, imidodiphosphate and pyrophosphate stimulated the enzyme with similar efficacies and potencies. Enzyme activation by GppNHp was most pronounced when [3H]PIP2 was used as substrate. No added Ca++ was required for [3H]PIP2 breakdown but hydrolysis was inhibited by divalent ion chelators. GppNHp stimulation was apparent in the presence of Ca++ or Mg++ as well as chelator concentrations that partially inhibited the enzyme, indicating that this effect was not attributed to changes in affinity of these divalent cations for the enzyme or substrate. These results suggest that guanine nucleotides can stimulate the hydrolysis of exogenous [3H]PIP2 in rat liver membranes by a non-specific effect probably due to the interaction of the diphosphate moiety with the enzyme or substrate.

Calcium↗
PubMed1999

Inhibition of human smooth muscle cell proliferation in culture by farnesyl pyrophosphate analogues, inhibitors of in vitro protein: farnesyl transferase.

In this study, it was investigated whether and how inhibitors of protein:farnesyl transferase (PFT) can inhibit the proliferation of human smooth muscle cells (HSMC) in culture. Several farnesyl pyrophosphate (FPP) analogues were synthesized and tested in vitro for their specificity in inhibiting squalene synthase (SS), PFT, or protein:geranylgeranyl transferase-1 (PGGT-1) activities (the latter was determined using a newly designed assay). One of these compounds appeared to be a strong PFT inhibitor (IC50 value: 340 nM) and a weak inhibitor in the other two enzyme assays. This compound (designated as TR006) inhibited the farnesylation of Ras in a Ha-ras transfected cell line (Cohen et al., Biochem. Phamacol. 49: 839-845, 1995) and concomitantly slowed down the growth of these cells. Twenty-five microM of TR006 inhibited the proliferation of HSMC isolated from left internal mammary artery, as measured by counting the cells over a period of three cell cycles (10 days). A structurally related compound (TR007), a specific SS inhibitor, did not influence HSMC proliferation under the same conditions. The inhibition by TR006 was concentration-dependent. In HSMC, synchronized by serum depletion, platelet-derived growth factor (PDGF) or basic fibroblast growth factor (bFGF)-induced DNA synthesis was decreased by a 29-hr pretreatment with 100 microM of TR006, indicating that this inhibitor acted in an early phase of the cell cycle, probably by preventing protein isoprenylation. Some other FPP analogues with comparable IC50 values in the in vitro PFT assay were also able to decrease bFGF-induced DNA synthesis without affecting cell viability. A more negatively charged member of this group, TR018, did not influence the growth factor-induced DNA synthesis, probably due to an impaired uptake into the cells. However, the pivaloyloxomethyl derivative of this compound, which is uncharged, and is thought to be converted into TR018 within the cells, showed a strong decrease in bFGF-induced DNA synthesis in HSMC. These data suggest that the compounds investigated may be developed further for treatment of conditions in which undesirable proliferation of smooth muscle cells plays an important role.

Alkyl and Aryl Transferases↗
PubMed1985

The inhibition of muscle contraction by adenosine 5' (beta, gamma-imido) triphosphate and by pyrophosphate.

We have studied the inhibition of the contraction of glycerinated rabbit psoas muscle caused by ligands that bind to the ATPase site of myosin. Two ligands, adenosine 5' (beta, gamma-imido) triphosphate (AMPPNP) and pyrophosphate (PPi), decreased the force and stiffness developed in isometric contractions and the velocity of shortening of isotonic contractions. The force exerted by isometric fibers was measured as a function of MgATP in the presence and absence of a constant concentration of the ligands. As the MgATP concentration decreased, the inhibition of tension caused by the ligand increased, reaching approximately 50% at 25 microM MgATP and either 2 mM MgPPi or 2 mM MgAMPPNP. The maximum velocity of shortening was also measured as a function of MgATP concentration in the presence of 1 and 2 mM MgPPi and 2.5 and 5 mM MgAMPPNP. Both ligands acted as pure competitive inhibitors with Ki = 3.0 mM for PPi and 5.1 mM for MgAMPPNP. These data show that both ligands are weak inhibitors of the contraction of fibers. The results provided information on the energetics of actin-myosin-ligand states that occur in the portion of the cross-bridge cycle where MgATP binds to myosin. A simple analysis of the inhibition of velocity suggests that MgAMPPNP binds to the actomyosin complex at this step of the cycle with an effective affinity constant of approximately 2 X 10(2) M-1.

Adenosine Triphosphate↗
PubMed1987

Possible cooperativity in crossbridge detachment in muscle fibers having magnesium pyrophosphate at the active site.

When rabbit psoas muscle fibers bathed in solutions containing the ATP analogue magnesium pyrophosphate (MgPPi) are first stretched rapidly and then held isometric, a force is generated during the stretch which decays during the subsequent isometric period (Schoenberg, M., and E. Eisenberg. 1985. Biophys. J. 48:863-871). Previously we showed that the force decay is due to crossbridge heads detaching and reattaching in positions of lesser strain, the rate of decay of force reflecting the crossbridge detachment rate constants. Since the crossbridge detachment rate constants with MgPPi bound to the active site are so much faster than without analogue bound, at subsaturating concentrations of analogue, if the heads act independently and nucleotide association and dissociation is rapid, the rate of force decay should simply be proportional to the number of heads with bound analogue. That is, the analogue concentration dependence of the rate of force decay should have the same form as the Michaelis-Menten equation. Here we report that the concentration dependence of the rate of force decay is not described by the Michaelis equation, but is instead sigmoidal. This suggests possible cooperativity in the detachment of the crossbridge heads, the amount of cooperativity being described by an interaction coefficient of approximately 2. One idea put forward to explain the data is that both of the heads of a crossbridge may need to bind analogue before the crossbridge can relax a substantial fraction of the tension it supports.

Adenosine Triphosphate↗
PubMed1992

Effects of magnesium pyrophosphate on mechanical properties of skinned smooth muscle from the guinea pig taenia coli.

Effects of the non-hydrolyzable nucleotide analogue magnesium pyrophosphate (MgPPi) on cross-bridge properties were investigated in skinned smooth muscle of the guinea pig Taenia coli. A "high" rigor state was obtained by removing MgATP at the plateau of an active contraction. Rigor force decayed slowly towards an apparent plateau of approximately 25-35% of maximal active force. MgPPi markedly increased the rate of force decay. The initial rate of the force decay depended on [MgPPi] and could be described by the Michaelis-Menten equation with a dissociation constant of 1.6 mM. The decay was irreversible amounting to approximately 50% of the rigor force. Stiffness decreased by 20%, suggesting that the major part of the cross-bridges were still attached. The results can be interpreted as "slippage" of PPi-cross-bridges to positions of lower strain. The initial rate of MgPPi-induced force decay decreased with decreasing ionic strength in the range 45-150 mM and was approximately 25% lower in thiophosphorylated fibers. MgADP inhibited the MgPPi-induced force decay with an apparent Ki of 2 microM. The apparent Km of MgATP for the maximal shortening velocity in thiophosphorylated fibers was 32 microM. This low Km of MgATP suggests that steps other than MgATP-induced detachment are responsible for the low shortening velocity in smooth muscle. No effects were observed of 4 mM MgPPi on the force-velocity relation, suggesting that cross-bridges with bound MgPPi do not constitute an internal load or that binding of MgPPi is weaker in negatively strained cross-bridges during shortening.

Adenosine Diphosphate↗
PubMed1978

Technetium 99Tcm pyrophosphate scanning in the assessment of the painful hip prosthesis.

Technetium 99Tcm pyrophosphate bone scans were done on 35 patients who complained of persistent hip following total hip replacement. The scans of six patients were normal and the symptoms of these patients either resolved (three) or greatly improved (three) without further treatment. Twenty-nine patients had abnormal scans. Seventeen of these were due to infection or loosening of the prosthesis. Paget's disease of bone, protrusion of the prosthesis and heterotopic ossification also caused scan abnormalities. These causes could not be distinguished from one another on the scan. A radiograph of the hip is essential for interpreting the scan correctly. Scanning of the painful hip prosthesis helps to detect patients in whom serious complications are present or are likely to develop.

Aged↗
PubMed1998

Diacylglycerol pyrophosphate: a novel metabolite in the Trypanosoma cruzi phosphatidic acid metabolism.

This work provides evidence that phosphatidic acid (PA) is metabolized to diacylglycerol pyrophosphate (DGPP) in Trypanosoma cruzi. Also the presence of the enzymatic activities involved in its regulation, phosphatidate kinase (PA-k) and phosphatidate phosphatase, is demonstrated. The increase of DGPP levels in T. cruzi epimastigotes or in its membrane fraction after exogenous PA addition or phospholipase (PLD) pre-treatment suggests that PA-k may be involved in the regulation of PA levels after its stimulation.

Animals↗
PubMed2003

Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-PtdIns(3,4,5)P3 interactions.

Inositol phosphates are well-known signaling molecules, whereas the inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (InsP7/IP7) and bis-diphosphoinositol tetrakisphosphate (InsP8/IP8), are less well characterized. We demonstrate physiologic regulation of Dictyostelium chemotaxis by InsP7 mediated by its competition with PtdIns(3,4,5)P3 for binding pleckstrin homology (PH) domain-containing proteins. Chemoattractant stimulation triggers rapid and sustained elevations in InsP7/InsP8 levels. Depletion of InsP7 and InsP8 by deleting the gene for InsP6 kinase (InsP6K/IP6K), which converts inositol hexakisphosphate (InsP6/IP6) to InsP7, causes rapid aggregation of mutant cells and increased sensitivity to cAMP. Chemotaxis is mediated by membrane translocation of certain PH domain-containing proteins via specific binding to PtdIns(3,4,5)P3. InsP7 competes for PH domain binding with PtdIns(3,4,5)P3 both in vitro and in vivo. InsP7 depletion enhances PH domain membrane translocation and augments downstream chemotactic signaling activity.

Amino Acid Sequence↗
PubMed1981

The effect of inorganic pyrophosphate (PPi) anions on the in vitro collagen fibril formation.

This paper presents a study on the effect of sodium salt of pyrophosphate (Na-PPi) in different concentrations (1-10 mMol/l) on the in vitro collagen fibril formation. Collagen was mixture of type I and III collagen dissolved in neutral buffer containing sodium chloride of 1.0 mol/l. Na-PPi added to collagen delayed the fibrillary precipitation of collagen from the solution. Electronmicroscopically the fibrils are of native collagen type, but they are thicker and show a pattern of fine substriation. Calcium and other divalent cations showed differences in their influence on the effect of Na-PPi. This experimental model was developed in order to interpret the supposed role of PPi in the inhibition of apatite crystal formations as well as the fibrogenic effect of its calcium salt in PPi-arthropathy. The effect of PPi on the collagen fibril formation should also be taken into consideration.

Animals↗
PubMed1997

Involvement and identification of a lysine in the PPi-site of pyrophosphate-dependent phosphofructokinase from Giardia lamblia.

The substrate binding and/or catalytic site of the pyrophosphate-dependent phosphofructokinase (PPi-PFK) of Giardia lamblia was investigated using an ATP affinity label, 2',3'-dialdehyde of ATP, oxidized ATP (oATP), for the involvement of lysine residues. The enzyme, which uses PPi rather than ATP as a substrate was inhibited by low concentrations of oATP. Oxidized ATP behaves as an affinity label for the substrate binding site as evidenced by saturation kinetics with the formation of reversible complex prior to inactivation, and the observation that the inactivation was stoichiometric with the amount of oATP incorporated which extrapolated to 1 mol per mol of monomeric PPi-PFK. The critical lysine modified by oATP is proposed to be located at the PPi-binding site since complete protection is afforded by PPi; and under steady-state, PPi was competitive with the inhibitor. Other substrates of the reaction in either the forward or reverse direction did not completely protect against inactivation. This is further confirmed by the non-competitive inhibition displayed by either Pi or fructose 1,6, bisphosphate. Furthermore, the Km values for Pi and fructose 1,6 bisphosphate of the oATP-modified enzyme were not altered. The oATP-modified peptides were analyzed by HPLC peptide mapping, and the profile showed a major peak absorbing at 258 nm, which was absent when the modification was carried out in the presence of MgPPi. This peptide was sequenced and found to contain Lys-497. These results suggest that the essential lysine-497 modified by oATP is involved in the binding and/or catalysis of PPi and that an ATP-type of binding domain, with reference to the phosphoryl groups, is present in the PPi-dependent phosphofructokinase of Giardia.

Adenosine Triphosphate↗
PubMedDate not supplied

Calcium pyrophosphate dihydrate crystal deposition disease: imaging perspectives.

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is widespread in elderly persons and has various clinical presentations that can be confounding to clinicians. It is characterized by acute, subacute, or chronic joint inflammation and deposition of CPPD crystals in hyaline cartilage, fibrocartilage, and other soft tissue structures. We have learned a great deal about imaging findings of CPPD crystal deposition disease. New facts about the disorder and clues to radiologic diagnosis continue to be revealed. This article will provide a review of imaging characteristics of this disease with emphasis on some recent findings. The nomenclature, epidemiology, classification, and pathophysiology will be explained. A discussion of the clinical manifestations and treatment will be followed by a review of the characteristic imaging features.

Aged↗
PubMed1996

Cubital tunnel syndrome associated with calcium pyrophosphate dihydrate crystal deposition disease.

Nine patients (11 elbows) presented with cubital tunnel syndrome that was complicated by calcium pyrophosphate dihydrate (CPPD) crystal deposition disease. Their age ranged from 63 to 86 years, and 8 of the 9 patients were more than 70 years old. X-ray film examination demonstrated the presence of CPPD crystal deposition not only in the elbow but also in the knee, wrist, or spine in all patients. Medial epicondylectomy was performed in 8 patients (9 elbows), while 1 patient with both elbows affected was treated conservatively at his request. Thickening of the ulnar collateral ligament and synovium due to CPPD crystal deposition and degenerative joint changes induced protrusion of the floor of the cubital tunnel, resulting in ulnar neuropathy in these patients. The ulnar nerve was compressed between the protruded floor and fibrous band. Though various causes of cubital tunnel syndrome have been reported, findings of this study indicate that CPPD crystal deposition disease should also be considered a cause of this syndrome.

Aged↗
PubMed1998

Calcium pyrophosphate dihydrate crystal deposition disease after anterior cruciate ligament reconstruction.

We report the case of a 34-year-old woman who presented with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease shortly after anterior cruciate ligament (ACL) reconstruction using a polyester artificial ligament (Leeds-Keio; Neoligaments, Leeds, England). The patient had earlier undergone a medial collateral ligament repair of a sprain to her right knee incurred while skiing. Nine years later, she underwent ACL reconstruction. Seventeen months after ACL reconstruction, calcification was observed on radiographs of the medial and lateral menisci. Based on these calcifications and polarized light microscopic findings of the joint fluid, the diagnosis was made of CPPD crystal deposition. CPPD deposition appeared to have resulted from intra-articular damage incurred during ACL reconstruction as well as prolonged anterior instability.

Adult↗