Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen dry Holstein cows were assigned four groups combining either .2 or 2.1% calcium and pH of either 4.5 or 6.1 in a 2 X 2 factorial arrangement of treatments to study the effect of diet calcium and acidity (pH) on voluntary intake of dry matter, mineral metabolism, and blood constituents. The 86-day experiment was started 84 days prepartum and completed 2 days postpartum. Voluntary dry matter ingestion tended to be higher with higher calcium and acidity (lower pH) diets. Calcium nutriture was improved by more acid diets. More total calcium was apparently absorbed (26 and 7 g) when the diet contained 2.1% calcium, but the .2% calcium diet resulted in a higher apparent percent absorption (25 and 17%) during the dry period. An increased apparent absorption (70 and 5 g) and utilization of diet calcium occurred with the higher calcium treatment at 2 days postpartum. Magnesium and phosphorus utilizations were improved with lower diet calcium. Although experimental treatments had no significant effect on blood minerals, serum calcium decreased 12% 2 days postpartum. A better calcium nutriture was provided by the higher calcium diets when the diets maintained a positive balance for magnesium and phosphorus.
 ...
PMID:Diet calcium and pH versus mineral balance in Holstein cows 84 days pre- to 2 days postpartum. 0 81

The pH within isolated Triton WR 1339-filled rat liver lysosomes was determined by measuring the distribution of [14C]methylamine between the intra- and extralysosomal space. The intralysosomal pH was found to be approximately one pH unit lower than that of the surrounding medium. Increasing the extralysosomal cation concentration lowered the pH gradient by a cation exchange indicating the presence of a Donnan equilibrium. The lysosomal membrane was found to be significantly more permeable to protons than to other cations. The relative mobility of cations through the lysosomal membrane is H+ greater than Cs+ greater than Rb+ greater than K greater than Na+ greater than Li+ greater than Mg2+, Ca2+. The presented data suggest that the acidity within isolated Triton WR 1339-filled lysosomes is maintained by: (1) a Donnan equilibrium resulting from the intralysosomal accumulation of nondiffusible anions and (2) a selective permeability of the lysosomal membrane to cations.
 ...
PMID:pH gradient across the lysosomal membrane generated by selective cation permeability and Donnan equilibrium. 23 54

The rate constant for the catalytic transfer of the active-site PO3 group from rabbit muscle phosphoglucomutase to the hydroxyl group of a water molecule is about 3 x 10(-8) s-1 under optimal reaction conditions, but in the absence of the normal substrate, viz., at pH 7.5 and 30 degrees C, in the presence of saturating Mg2+; the corresponding constant for transfer to the 6-hydroxyl group of glucose 1-phosphate under analogous conditions, about 1000 s-1, is larger than this by some 3 x 10(10)-fold. Since no single factor appears to be capable of providing a rationale for a majority of this "substrate-induced rate effect" (Ray, jr., W.J., and Long, J.W. (1976), Biochemistry, the preceding paper in this issue), the change in the PO3-transfer rate produced by binding various parts of the phosphoglucosyl moiety to the enzyme, both separately and concurrently, was investigated. The rate of PO3 transfer to water is increased by up to 1000-fold by binding entities that provide the active site with a second PO3 group, e.g., ethyl phosphate or inorganic phosphite. Using an alcoholic acceptor further increases transfer efficiency (in the presence of bound phosphite): increase with methanol, about 2000-fold on a molar basis. The reactivities of ten other primary aliphatic alcohols vary by nearly 600-fold as the acidity of the PO3 acceptor is varied over a 4000-fold range. Although no straightforward relationship is observed between the efficiency of an alcohol as an acceptor and its acidity - presumably because of complications due to steric effects, for example - an increased transfer rate of 100-fold, relative to the water reaction, is estimated for a simple primary alcohol with a pKa similar to that expected for the 6-hydroxyl group of glucose 1-phosphate, when the alcohol is present at a concentration of 1 M. Joining an alcoholic acceptor and a PO3 group via five apparently inert bridging units changes PO3 transfer to an intramolecular process; in the case of 1,4-butanediol monophosphate the rate of transfer also increases by 240-fold, relative to the analogous reaction in the presence of 1 M propanol and bound inorganic phosphite. Comparable values also are obtained in comparisons of PO3 transfer rates for trans- 1,4-butenediol and 1,4-butynediol monophosphates relative to 1 M allyl and propargyl alcohols, respectively, in the presence of bound phosphite. An increased rate of transfer also is produced by binding the xylosyl part of the glucose ring, either when the acceptor is an hydroxyl group attached to the ring or when it is the hydroxyl group of a water molecule, e.g., as in the water reaction facilitated by bound xylose 1-phosphate. These and other results suggest that most of the differences between the rates of the water reaction and the glucose 1-phosphate reaction can be rationalized in terms of four fairly discrete factors whose approximate values are as follows: the PO4 factor, 1000-fold; the C-OH/H-OH factor, 100-fold; the nucleophile-binding factor, 250-fold; and the (CHOH)3-bridging factor, 200-fold...
 ...
PMID:An analysis of the substrate-induced rate effect in the phosphoglucomutase system. 96 19

In the amoeba, Dictyostelium discoideum, endocytic vacuoles are acidified by proton pumps which reside not in their membranes but in an associated organelle which we call the acidosome. These two organelles can be dissociated in vitro, and we now describe conditions for their functional reassociation. Fluorescein 5-isothiocyanate-dextran was fed to amoebae to report on the pH of their endocytic vacuoles. Following homogenization, the endocytic vacuoles were dissociated from acidosomes by removing Mg2+ and cytosol and purged of their native acidity by transient exposure to nigericin. The endocytic vacuoles could then be reacidified by ATP if first preincubated under these optimized conditions: 30 degrees C for 30 min in the presence of acidosomes, a 4-fold excess of cytosol, and 5 mM Mg2+ at pH 7.4. Reacidification was observed with early but not late endocytic compartments. Mn2+ and Ca2+ were poor substitutes for Mg2+; albumin did not substitute for cytosol. Neither Ca2+, ATP, nor adenosine 5'-O-(3-thiotriphosphate) affected reconstitution appreciably; guanosine 5'-O-(3-thiotriphosphate) inhibited reacidification by 50% when present during preincubation at 0.1 mM. Warming the cytosol to 50 degrees C or exposing it to protease abolished its activity but N-ethylmaleimide did not. Molecular sieving indicated that the cytosolic factor was a macromolecule. We conclude that the specific functional association of acidosomes and endocytic vacuoles can be reconstituted in vitro with soluble proteins plus Mg2+.
 ...
PMID:Reconstitution of the association of endocytic vacuoles and acidosomes from Dictyostelium. 164 80

The endocytic compartment in the amoeba Dictyostelium discoideum was labeled by feeding fluorescein 5-isothiocyanate-dextran. In homogenates containing 2 mM Mg2+, the compartments so labeled copurified with all of the vacuolar H(+)-ATPase activity in a dense peak. The fluorescence properties of the probe showed that these dense vacuoles were inherently acidic. Furthermore, after purging their residual acidity, they could be re-acidified by the addition of ATP. These data suggest that the H(+)-ATPase was structurally and functionally coupled to the endocytic space. The association of the H(+)-ATPase and endocytic compartment was reversed by the removal of either Mg2+ or traces of the cytosol. Endocytic vacuoles prepared in this way were deficient in vacuolar H(+)-ATPase activity and were not acidified upon addition of MgATP. The missing proton pumps were recovered in large buoyant vacuoles that lacked ingested fluorescein 5-isothiocyanate-dextran, acid hydrolases, and residual acidity. These vacuoles were also less susceptible than endosomes to disruption by digitonin, suggesting that their bilayers were low in sterols. These results indicate that the endocytic circuit in Dictyostelium is acidified by a discrete and separable proton-pumping organelle.
 ...
PMID:Endosomes are acidified by association with discrete proton-pumping vacuoles in Dictyostelium. 170 36

We have studied the mechanism by which liver Golgi apparatus maintains the acidity of its contents, using a subcellular fraction from rat liver highly enriched in Golgi marker enzymes. Proton accumulation (measured by quenching of acridine-orange fluorescence) and anion-dependent ATPase were characterized and compared. Maximal ATPase and proton accumulation required ATP; GTP and other nucleotides gave 10% to 30% of maximal activity. Among anions, Cl- and Br- approximately doubled the activities; others were much less effective. Half-maximal increase of ATPase and H+ uptake required 55 mmol/L and 27 mmol/L Cl-, respectively. In predominantly chloride media, SCN- and NO3- markedly inhibited H+ uptake. Nitrate competitively inhibited both the chloride-dependent ATPase (apparent Ki 6 mmol/L) and proton uptake (apparent Ki 2 mmol/L). Nitrate and SCN- also inhibited uptake of 36Cl. Replacing K+ with Na+ had no effect on the initial rate of proton uptake but somewhat reduced the steady state attained. Replacement of K+ with NH4+ and choline reduced proton uptake without affecting ATPase. The ATPase and H+ uptake were supported equally well by Mg2+ or Mn2+. The ATPase was competitively inhibited by 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid (apparent Ki 39 mumol/L). Other agents inhibiting both H+ uptake and ATPase were N-ethylmaleimide, N,N'-dicyclohexylcarbodiimide, chlorpromazine, diethylstilbestrol, Zn2+, Co2+ and Cu2+. In the Cl- medium, accumulated protons were released by ionophores at the relative rates, monensin = nigericin greater than valinomycin greater than carbonyl cyanide mchlorophenylhydrazone; the last of these also reduced ATPase activity. In the absence of Cl-, monensin and valinomycin both stimulated the ATPase. These results show a close association between ATPase activity and acidification of liver Golgi vesicles. They support a role for Cl- that depends on its uptake as a counter ion for H+ and suggest that it may also stimulate proton transport by a more direct effect on a component of the transport system.
 ...
PMID:Proton accumulation and ATPase activity in Golgi apparatus-enriched vesicles from rat liver. 184 95

Membranes from Halobacterium saccharovorum contained a cryptic ATPase which required Mg2+ or Mn2+ and was activated by Triton X-100. The optimal pH for ATP hydrolysis was 9-10. ATP or GTP were hydrolyzed at the same rate while ITP, CTP, and UTP were hydrolyzed at about half that rate. The products of ATP hydrolysis were ADP and phosphate. The ATPase required high concentrations (3.5 M) of NaCl for maximum activity. ADP was a competitive inhibitor of the activity, with an apparent Ki of 50 microM. Dicyclohexylcarbodiimide (DCCD) inhibited ATP hydrolysis. The inhibition was marginal at the optimum pH of the enzyme. When the ATPase was preincubated with DCCD at varying pH values, but assayed at the optimal pH for activity, DCCD inhibition was observed to increase with increasing acidity of the preincubation medium. DCCD inhibition was also dependent on time of preincubation, and protein and DCCD concentrations. When preincubated at pH 6.0 for 4 h at a protein:DCCD ratio of 40 (w/w), ATPase activity was inhibited 90%.
 ...
PMID:Dicyclohexylcarbodiimide-sensitive ATPase in Halobacterium saccharovorum. 293 Oct 49

Affinity labeling and comparative sequence analyses have placed Lys-166 of ribulosebisphosphate carboxylase/oxygenase from Rhodospirillum rubrum at the active site. The unusual nucleophilicity and acidity of the epsilon-amino group of Lys 166 (pKa = 7.9) suggest its involvement in catalysis, perhaps as the base that enolizes ribulosebisphosphate (Hartman, F.C., Milanez, S., and Lee, E.H. (1985) J. Biol. Chem. 260, 13968-13975). In attempts to clarify the role of Lys-166 of the carboxylase, we have used site-directed mutagenesis to replace this lysyl residue with glycine, alanine, serine, glutamine, arginine, cysteine, or histidine. All seven of these mutant proteins, purified by immunoaffinity chromatography, are severely deficient in carboxylase activity; the serine mutant, which is the most active, has a kcat only 0.2% that of the wild-type enzyme. Although low, the carboxylase activity displayed by some of the mutant proteins proves that Lys-166 is not required for substrate binding and argues that the detrimental effects brought about by amino acid substitutions at position 166 do not reflect gross conformational changes. As demonstrated by their ability to tightly bind a transition-state analogue (2-carboxyarabinitol 1,5-bisphosphate) in the presence of CO2 and Mg2+, some of the mutant proteins undergo the carbamylation reaction that is required for activation of the wild-type enzyme. Since Lys-166 is required neither for activation (i.e. carbamylation by CO2) nor for substrate binding, it must be essential to catalysis. When viewed within the context of previous related studies, the results of site-directed mutagenesis are entirely consistent with Lys-166 functioning as the base that initiates catalysis by abstracting the C-3 proton from ribulosebisphosphate. An alternative possibility that Lys-166 acts to stabilize a transition state in the reaction pathway cannot be rigorously excluded.
 ...
PMID:Function of Lys-166 of Rhodospirillum rubrum ribulosebisphosphate carboxylase/oxygenase as examined by site-directed mutagenesis. 310 87

The ionic compensatory response to CO2 breathing for 3 days was studied on intact and cystectomized turtles at 10 and 20 degrees C. Arterial blood gases, pH, ionized calcium, and the plasma concentrations of Na+, K+, Cl-, total Ca2+, and total Mg2+ were measured periodically. At 20 degrees C, ureteral urine was also collected from bladderless turtles and was analyzed for pH, ions, NH3+, total CO2, osmolality, and titratable acid. When CO2 was breathed there was a compensatory change in the strong-ion difference as manifest by an increase in plasma [HCO3-] that was approximately 10 meq/l both in the 10 and 20 degrees C turtles. The only significant associated strong-ion changes observed consistent with the ionic compensatory response were increases in total and ionized Ca2+ and total Mg2+. These results were unaffected at either temperature by surgical removal of the urinary bladder. Urine collected from cystectomized turtles showed no compensatory increase in acid excretion during hypercapnia; in fact, changes occurred in the opposite direction. Urinary excretion of HCO3- and urine pH increased significantly, whereas titratable acidity decreased significantly. No significant change occurred in ammonia excretion over the three days of hypercapnia. These data argue against compensatory roles for the kidneys and urinary bladder in this species and point to internal ionic exchanges involving bone and shell.
 ...
PMID:Ionic compensation with no renal response to chronic hypercapnia in chrysemys picta bellii. 378 4

Losses of Ca2+, Mg2+ and primary amines into waters between pH = 5 and 3 from eyed Chinook salmon eggs, Oncorhynchus tshawytscha , and gills excised from the freshwater, bivalve mollusc Anodonta californiensis were measured and compared to effluxes into distilled water. Sulfuric, nitric and hydrochloric acids were used. Even at pH = 5 losses of Ca2+ and Mg2+ from both biological systems occur at short times, minutes, and can exceed those found in water of higher pH (non-acid waters). Increasing acidity increases short term primary amine loss from both systems. For both divalent cation and amino acid losses gills of A. californiensis are more sensitive to acidity than eggs of O. tshawytscha .
 ...
PMID:The effect of acid water on the loss of divalent cations and primary amines from natural membranes. 614 37


1 2 3 4 5 6 7 8 Next >>